Dilatation Of Artery Research Articles

Abstract 3133: Selective Vulnerability Of Coronary Arteries To Hypercholesterolemia And Angiotensin II-induced Hypertension

Hypercholesterolemia and hypertension are major risk factors for cardiovascular disease. We aimed to determine their concomitant effects on coronary atherogenesis. An SR-BI (an HDL receptor) suppression and doxycycline-inducible angiotensin II (AngII) cassette was inserted downstream of the ApoE promoter to ablate ApoE expression and overproduce AngII. The resulting mutants (ApoE SA/SA ) exhibited mild coronary atherosclerosis after Western diet feeding. Doxycycline induced AngII-induced hypertension and drastically accelerated coronary atherosclerosis, with lesions exhibiting endothelial erosion, myeloid cell infiltration, and plaque rupture, resulting in myocardial infarction, heart failure, and male-propensity of sudden death. AngII, but not norepinephrine-induced hypertension, led to severe coronary atherogenesis under hypercholesterolemia, which was abolished by losartan. Notably, norepinephrine constricted femoral arteries, but it dilated coronary arteries. In contrast to coronary arteries, femoral arteries did not develop atherosclerosis. Proteomic analyses revealed distinctive differences between the two vascular beds. Coronary vasodilation to acetylcholine was highly susceptible to the risk factors, compared to femoral artery, and was markedly attenuated by AngII exposure and prostaglandin inhibition. Interestingly, coronary prostaglandin synthesis was suppressed in atherogenesis, and elevated coronary capacity to produce prostaglandins following methotrexate administration was associated with ameliorated early coronary endothelial dysfunction and improved cardiovascular survival, featuring markedly reduced lesional myeloid cells. Coronary arteries from patients with hypertension and hypercholesterolemia showed substantially impaired endothelium-dependent vasodilation, compared to internal mammary arteries of similar risk exposure, whereas their endothelium-independent vasodilation was intact. Thus, the combination of hypercholesterolemia and AngII-induced hypertension drastically promoted coronary atherosclerosis with spontaneous lesion rupture, which confers a selective vulnerability of coronary vasodilation to prostaglandin inhibition and AngII exposure.

Relationship between ocular manifestations, laboratory findings, echocardiographic findings, and intravenous immunoglobulin resistance in Kawasaki disease.

This study investigates the incidence of ocular involvement in Kawasaki disease (KD) and evaluates the relationship between ocular manifestations, laboratory findings, echocardiographic findings, and intravenous immunoglobulin (IVIG) resistance. We conducted a cross-sectional study with 58 KD patients from June 2021 to March 2023. For all patients, a complete ophthalmologic examination and echocardiography were performed in the acute phase before starting the treatment. We analyzed the age, sex, mean of white blood cell (WBC) count, platelet count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), echocardiographic findings and IVIG responses for all patients and compared the group with ocular involvement with the group without involvement. The incidence of bilateral acute conjunctivitis was 70.7%, while that of acute uveitis was 30%. Patients with uveitis had significantly higher rates of Coronary artery dilatation and IVIG resistance, as well as higher mean levels of WBC, platelet, and CRP compared to those without uveitis. (P < 0.05). Additionally, the age of patients with uveitis involvement was lower than those without involvement. No significant relationships existed between ESR, AST, or ALT values and uveitis (P > 0.05). Furthermore, no significant correlations existed between any examined items and acute bilateral conjunctivitis. Uveitis in KD is significantly associated with coronary artery dilatation, IVIG resistance, higher WBC count, platelet count, and CRP level.

Estrogen stimulates fetal vascular endothelial growth factor expression and microvascularization.

We recently showed that the ratio of capillaries to myofibers in skeletal muscle, which accounts for 80% of insulin-directed glucose uptake and metabolism, was reduced in baboon fetuses in which estrogen was suppressed by maternal letrozole administration. Since vascular endothelial growth factor (VEGF) promotes angiogenesis, the present study determined the impact of estrogen deprivation on fetal skeletal muscle VEGF expression, capillary development, and long-term vascular and metabolic function in 4- to 8-year-old adult offspring. Maternal baboons were untreated or treated with letrozole or letrozole plus estradiol on days 100-164 of gestation (term = 184 days). Skeletal muscle VEGF protein expression was suppressed by 45% (P < 0.05) and correlated (P = 0.01) with a 47% reduction (P < 0.05) in the number of capillaries per myofiber area in fetuses of baboons in which serum estradiol levels were suppressed 95% (P < 0.01) by letrozole administration. The reduction in fetal skeletal muscle microvascularization was associated with a 52% decline (P = 0.02) in acetylcholine-induced brachial artery dilation and a 23% increase (P = 0.01) in mean arterial blood pressure in adult progeny of letrozole-treated baboons, which was restored to normal by letrozole plus estradiol. The present study indicates that estrogen upregulates skeletal muscle VEGF expression and systemic microvessel development within the fetus as an essential programming event critical for ontogenesis of systemic vascular function and insulin sensitivity/glucose homeostasis after birth in primate offspring.

Individuals with Post-COVID Conditions Exhibit Delayed Vasodilatory Response following Brachial Artery Occlusion in the Absence of Endothelial Dysfunction and Arterial Stiffness

Background: Post-COVID Conditions (PCC) is a disorder in which individuals who contract the SARS-CoV-2 virus experience prolonged symptoms such as fatigue beyond 4 weeks after initial infection. Preliminary data suggest that individuals who are acutely infected display increased arterial stiffness and endothelial dysfunction, as well as autonomic dysfunction. However, it is not well understood if individuals with PCC continue to experience these dysfunctions beyond acute infection. Therefore, this study aimed to investigate whether vascular and autonomic function are impaired in individuals with PCC compared to individuals without PCC. Methods: Individuals previously infected with the SARS-CoV-2 virus at least 4 weeks prior to participation in the study had vascular and autonomic function assessed at baseline. Individuals experiencing PCC symptoms were classified as symptomatic (SYM, n=12) and individuals without PCC symptoms were classified as asymptomatic (ASYM, n=9). Participants were matched for age (30-55 years) and date since SARS-CoV-2 infection (ranging from 1-12 months). Arterial stiffness (carotid-femoral pulse wave velocity, cfPWV via tonometry), common carotid artery b-stiffness (via ultrasonography and tonometry), and endothelial function (brachial artery flow-mediated dilation, baFMD via ultrasonography) were assessed. Time-to-peak vasodilation (TTP) was assessed from baFMD as the time after cuff release until peak brachial artery dilation. Autonomic function was assessed with spontaneous cardiovagal baroreflex sensitivity (BRS) via sequence technique. Results: At baseline, there were no differences between groups in cfPWV (SYM: 6.2 ± 0.7 m/s, ASYM: 6.3 ± 1.1 m/s; p=0.90), baFMD (SYM: 7.3 ± 6.1%, ASYM: 7.7 ± 5.6%; p=0.87), brachial artery baseline diameter (SYM: 3.4 ± 0.6 mm, ASYM: 3.2 ± 0.4 mm; p=0.37) and common carotid b-stiffness index (SYM: 9.2 ± 2.1U, ASYM: 8.2 ± 2.5U; p=0.360). Despite no differences in baFMD% between groups, the SYM group had a significantly higher baseline baFMD TTP compared with the ASYM group (SYM: 61.6 ± 23.1 s, ASYM: 36.8 ± 14.3 s; p=0.010). There were no significant differences in cardiovagal BRS (SYM: 10.9 ± 6.8 ms/mmHg, ASYM: 11.8 ± 2.6 ms/mmHg; p=0.80). Conclusions: While arterial stiffness, endothelial function and baroreflex function did not differ between groups, individuals with PCC did present with delayed peak brachial artery vasodilation in response to shear stress. These data suggest any possible effects on vascular and autonomic function from acute SARS-CoV2 infection appear to be resolved beyond 4 weeks in those who experience prolonged symptoms. However, the delayed vasodilatory response may indicate some level endothelial dysfunction that persists in individuals with PCC. Funded by: Russell B. Day and Florence D. Day Chair in Liberal Arts and Sciences fund. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

High altitude sojourn elicits divergent effects in aortic and carotid stiffness in healthy-young adults

High altitude exposure challenges the cardiovascular system to compensate for barometric pressure-mediated reductions in arterial oxygen content. Reductions in oxygen content elicit simultaneous increases in sympathetic nervous system activity and vasodilation that may have competing effects on changes in large artery stiffness. The objective of this study was to examine changes in aortic and carotid stiffness during high altitude sojourn in healthy, young adults. We hypothesized that short-term high-altitude sojourn would increase both aortic and carotid stiffness. 17 Generally healthy adults (23±4 yrs, 25.0±3.0 BMI, n=9 females) underwent vascular assessments in the supine position at 1400 m and after an 8-day incremental ascent to 4300 m. Aortic stiffness and carotid β-stiffness were derived from carotid-femoral pulse wave velocity (cfPWV) via applanation tonometry and right common carotid artery ultrasonography, with blood pressure assessed via oscillometry. Ascent from 1400 m to 4300 m resulted in decreased arterial oxygen saturation (-11±4 %, p&lt;0.001) and carotid β-stiffness (-4.48±2.73 au, p&lt;0.001), and increased cfPWV, (+54.98±78.10 cm/s, p=0.01) and mean arterial pressure (+4±7 mmHg, p=0.02). Changes in cfPWV, arterial oxygen saturation, and blood pressure were moderately to strongly correlated (r=-0.425-0.503, p=0.09-0.04). Our data suggest that short term exposure to high altitude has differential effects on carotid versus aortic stiffness despite increases in mean blood pressure. Increases in aortic stiffness appear related to hypoxia-induced reductions in arterial oxygen saturation and concomitant increases in blood pressure, while reductions in carotid stiffness may stem, in-part, from compensatory carotid artery dilation necessary to increase cerebral blood flow at high altitude. Additional research is necessary to further understand mechanisms underlying differential changes in large artery stiffness during high altitude sojourn. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Endogenous Acetylcholine Contributes to Flow-Mediated Dilation in Humans

Background &amp; Objective. Flow-mediated dilation (FMD) is a crucial function of the vascular endothelium wherein intraluminal shear stress stimulates endothelium-dependent vasodilation mediated primarily by nitric oxide. Brachial artery FMD (baFMD) is widely evaluated in clinical research as an index of endothelial function, and impaired baFMD is an independent predictor of cardiovascular risk. Despite the physiological and clinical relevance of FMD, the mechanisms by which shear stress is transduced to endothelium-dependent vasodilation (i.e., upstream of nitric oxide production) remain unclear. baFMD corresponds closely with sensitivity to the endothelium-dependent vasodilator acetylcholine (ACh), and preclinical models suggest ACh is released from endothelial cells in response to shear stress. Therefore, the present study tested the hypothesis that activation of muscarinic ACh receptors facilitates baFMD in humans. Methods. baFMD was evaluated using Doppler ultrasound in healthy participants (n=11; 5F/6M; 23±2 y; means ± SE) under control conditions and following local inhibition of muscarinic ACh receptors via intra-arterial atropine infused proximal to the measurement site. baFMD was assessed in response to transient and sustained shear stimuli in separate trials: 1) reactive hyperemia following 5 min of arterial cuff occlusion (RH-FMD) and 2) steady-state rhythmic handgrip exercise at graded intensities (10, 15, 20, &amp; 25% maximal voluntary contraction, MVC) to produce step increases in shear rate (EX-FMD). Blockade effcacy was confirmed via a dose-response to intra-arterial ACh infusion pre and post atropine. Results. Baseline brachial artery diameter and forearm blood flow were similar in all trials (all P&gt;0.05). Atropine reduced peak brachial artery dilation following cuff release (RH-FMD, Δ diameter, atropine: 4.6±0.8 vs. control: 6.5±0.8%, P=0.04) and increased the shear stimulus (shear rate area under the curve, SRAUC: atropine, 29±3 vs. control: 21±3 s−1×103, P=0.01) such that the percent change in brachial diameter was diminished by 35±16% when normalized to SRAUC (baFMD:SRAUC ratio, atropine: 1.7±0.3 vs. control: 3.9±1.0, P=0.02). Similarly, in the EX-FMD trial, atropine reduced brachial artery diameter at all exercise intensities (25% MVC, percent change in diameter: atropine, 10.8±1.4 vs. control, 15.5±1.7%, P=0.04) despite a greater shear stimulus (shear rate: atropine, 10.9±1.1 vs. control, 9.3±0.9 s−1×102, P=0.01). Thus, atropine reduced the slope describing the relationship between brachial artery vasodilation (percent change) and the change in shear rate by 38±8% across all exercise intensities (slope, atropine: 1.3±0.1 vs. control: 2.4±0.4% Δ×s×10−2, P=0.007). As expected, atropine reduced brachial artery vasodilation in response to upstream infusion of ACh (1.5 μg ACh/dl forearm volume/min, Δ diameter, atropine: 2±1 vs. control: 23±4%, P=0.001). Conclusions. The results suggest endogenous ACh facilitates baFMD in response to both transient and sustained shear stimuli, which highlights a novel physiological role of endogenous ACh in vascular regulation in humans and provides insight regarding the basic mechanisms of flow-mediated vasodilation. NIH R01 HL119337 and F31 HL142240. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Nitrate-rich beetroot juice supplementation in midlife and older adults with renal dysfunction increases vascular endothelial function and changes the circulating milieu to improve endothelial cell nitric oxide production and oxidative stress

BACKGROUND: Midlife and older (ML/O) adults with mild-to-moderate renal dysfunction (MRD) are at increased risk for cardiovascular disease (CVD). A key antecedent to CVD in ML/O adults with MRD is vascular endothelial dysfunction, mediated by declines in nitric oxide (NO) bioavailability due to excess reactive oxygen species (ROS)-related oxidative stress. We have shown that targeting the nitrate-nitrite-NO pathway with sodium nitrite in heathy ML/O adults improves endothelial function and changes the circulating milieu to lower endothelial cell (EC) ROS bioactivity. However, if nitrate-rich beetroot juice (N-BRJ) is effective for improving endothelial function in ML/O men and women with MRD is unknown. HYPOTHESES: We tested the hypotheses that chronic N-BRJ in ML/O men and women with MRD would: 1) improve endothelial function and 2) induce changes to the circulating milieu to increase EC NO production and lower EC ROS bioactivity. We also assessed possible sex differences in the effcacy of N-BRJ for improving endothelial function. METHODS: Twenty-six ML/O men and women with MRD (estimated glomerular filtration rate [eGFR; CKD-EPI]: 40-89 mL/min/1.73m2) underwent three months of supplementation with N-BRJ (70 mL with 6.45 mmol nitrate/day) (n=13, 7 women; age: 65±2 years; eGFR: 69.2±3.3 mL/min/1.73m2) or nitrate-depleted BRJ (placebo, PBO) (n=13, 7 women; age: 68±2 years; eGFR: 79.8±3.1 mL/min/1.73m2) in a randomized, placebo-controlled, parallel-group design clinical trial. Endothelial function was assessed by brachial artery flow-mediated dilation (FMDBA). Smooth muscle sensitivity to NO was assessed by brachial artery dilation to sublingual nitroglycerin. Human aortic ECs (HAECs) in culture were exposed to 10% subject serum (n=10[6-7 women]/group) collected before and after N-BRJ and PBO supplementation. Acetylcholine-stimulated NO production (DAR-4M-AM) and whole-cell ROS bioactivity (CellROX) were assessed in HAECs using immunofluorescence. Results: N-BRJ supplementation increased FMDBA by 28% (pre: 4.6±0.7%, post: 5.9±0.8%; p=0.03). FMDBA did not change with PBO (pre: 4.6±0.9%, post: 4.7±0.8%; p&gt;0.05). Traditional CVD risk factors (i.e., blood pressure, cholesterol) and smooth muscle sensitivity to NO were unchanged in both groups (p&gt;0.05). Preliminary assessments suggest greater improvements in endothelial function with N-BRJ in women (Δ=post-pre intervention; ΔFMDBA=1.6±0.4) compared to men (ΔFMDBA=0.9±1.0). Compared to pre-intervention, NO production was (trending) 7% higher (p=0.05) and ROS bioactivity was 25% lower (p=0.02) in HAECs exposed to serum collected post N-BRJ. Serum from PBO had no effects (p&gt;0.05). CONCLUSION: N-BRJ supplementation in ML/O adults with MRD holds promise for improving endothelial function, in part by inducing changes to the circulating milieu that increase NO production and decrease oxidative stress in ECs. The effects on endothelial function may be greater in women compared to men. Targeting the nitrate-nitrite-NO pathway with N-BRJ may be an effective strategy for improving endothelial function in ML/O adults with renal dysfunction to possibly reduce CVD risk. K01DK115524 (MJR); R01AG013038 (DRS); F32HL167552 (KOM); NIH/NCATS CTSA UL1TR002535. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Deletion of Sigmar1 leads to increased arterial stiffness and altered mitochondrial respiration resulting in vascular dysfunction.

Sigmar1 is a ubiquitously expressed, multifunctional protein known for its cardioprotective roles in cardiovascular diseases. While accumulating evidence indicate a critical role of Sigmar1 in cardiac biology, its physiological function in the vasculature remains unknown. In this study, we characterized the expression of Sigmar1 in the vascular wall and assessed its physiological function in the vascular system using global Sigmar1 knockout (Sigmar1-/-) mice. We determined the expression of Sigmar1 in the vascular tissue using immunostaining and biochemical experiments in both human and mouse blood vessels. Deletion of Sigmar1 globally in mice (Sigmar1-/-) led to blood vessel wall reorganizations characterized by nuclei disarray of vascular smooth muscle cells, altered organizations of elastic lamina, and higher collagen fibers deposition in and around the arteries compared to wildtype littermate controls (Wt). Vascular function was assessed in mice using non-invasive time-transit method of aortic stiffness measurement and flow-mediated dilation (FMD) of the left femoral artery. Sigmar1-/- mice showed a notable increase in arterial stiffness in the abdominal aorta and failed to increase the vessel diameter in response to reactive-hyperemia compared to Wt. This was consistent with reduced plasma and tissue nitric-oxide bioavailability (NOx) and decreased phosphorylation of endothelial nitric oxide synthase (eNOS) in the aorta of Sigmar1-/- mice. Ultrastructural analysis by transmission electron microscopy (TEM) of aorta sections showed accumulation of elongated shaped mitochondria in both vascular smooth muscle and endothelial cells of Sigmar1-/- mice. In accordance, decreased mitochondrial respirometry parameters were found in ex-vivo aortic rings from Sigmar1 deficient mice compared to Wt controls. These data indicate a potential role of Sigmar1 in maintaining vascular homeostasis.

Comparison of six Z-score formulas based on echocardiography for coronary artery lesions in Kawasaki disease

GoalKawasaki disease (KD) patients are at risk of developing the serious complication of coronary artery dilation (CAD). To diagnose CAD caused by KD, various Z-Score formulas are used worldwide. This paper aims to evaluate the differences and inclusiveness among the six most commonly used Z-Score formulas in diagnosing CAD in Suzhou, China. Additionally, the study seeks to compare the differences in CAD diagnosis among different high-risk factor groups. By doing so, this research provides a valuable reference for accurately diagnosing CAD in KD patients. MethodThis paper presents a retrospective analysis of 1509 patients diagnosed with KD at the Children's Hospital of Soochow University between January 2018 and December 2020. We collected the patients' clinical and echocardiographic data and used six Z-Score formulas (Kobayashi et al., de Zorzi et al., Kurotobi et al., McCrindle et al., Olivieri et al., and Dallaire et al.) to diagnose the degree of CAD in different segments. We then compared the diagnostic differences and inclusiveness of these formulas, especially the diagnostic differences in medium to giant CAA. To achieve this, we divided the patients into groups based on their age (≤12 months, 13–30 months, and > 30 months) and fever duration (≤5 days, 6–7 days, 8–9 days, and ≥ 10 days). Using the McNemar test and the Kappa test, we compared the differences and the consistencies of CDA diagnosis among the six Z-Score formulas. Moreover, we used the Friedman test and Chi-square segmentation formula to compare the differences in age and number of fever duration between groups and to compare each Z-Score formula pair within the group. ResultsExcept for the LMCA segment, where there were no statistically significant differences between de Zorzi formula and McCrindle formula, the Z-score formulas showed statistically significant differences in the degree of CAD diagnosis across all other segments. Inclusiveness assessment revealed that Kobayashi formula and Dallaire formula showed significantly higher rates of dilatation (6.58% and 5.32%), or of small aneurysms (6.52% and 4.52%) compared to other formulas (1.0%–1.73%). Medium aneurysms were also more likely to be identified with Kobayashi and Dallaire formulas (0.8% and 0.8%) compared to the remaining formulas (0.13–0.40%). There are significant differences in the diagnoses of medium to giant CAA made by these six formulas in LAD and RCA. The longer the duration of fever and the younger the age, the higher the diagnosis rates of CAD and CAA. There were no statistically significant differences between de Zorzi formula and McCrindle formula, de Zorzi formula and Oliveri formula, and Kurotobi formula and Dallaire formula within the four groups based on the duration of fever. Similarly, there were no statistically significant differences between Kobayashi formula and Dallaire formula, and between de Zorzi formula and Oliveri formula in the age groups of ≤12 months and 13–30 months. ConclusionThere are diagnostic differences among these six Z-score formulas, considering the aforementioned statistics. Kobayashi formula and Dallaire formula are more inclusive, and less likely to under-diagnose significant CAD. They perform evenly for dilatation only, for small aneurysms and the median size aneurysms, and that is for segments of LMCA, LAD and RCA. In addition, McCrindle formula joins the “inclusive” pack for LAD and RCA in the matter of CAD. The younger the age of the patients and the longer the duration of fever, the higher the diagnosis rates of CAD and CAA. Furthermore, the younger the age of the patients and the shorter the duration of fever, the greater the differences between the various formulas.

P2X7 receptor knockout does not alter renal function or prevent angiotensin II-induced kidney injury in F344 rats

P2X7 receptors mediate immune and endothelial cell responses to extracellular ATP. Acute pharmacological blockade increases renal blood flow and filtration rate, suggesting that receptor activation promotes tonic vasoconstriction. P2X7 expression is increased in kidney disease and blockade/knockout is renoprotective. We generated a P2X7 knockout rat on F344 background, hypothesising enhanced renal blood flow and protection from angiotensin-II-induced renal injury. CRISPR/Cas9 introduced an early stop codon into exon 2 of P2rx7, abolishing P2X7 protein in kidney and reducing P2rx7 mRNA abundance by ~ 60% in bone-marrow derived macrophages. The M1 polarisation response to lipopolysaccharide was unaffected but P2X7 receptor knockout suppressed ATP-induced IL-1β release. In male knockout rats, acetylcholine-induced dilation of the renal artery ex vivo was diminished but not the response to nitroprusside. Renal function in male and female knockout rats was not different from wild-type. Finally, in male rats infused with angiotensin-II for 6 weeks, P2X7 knockout did not reduce albuminuria, tubular injury, renal macrophage accrual, and renal perivascular fibrosis. Contrary to our hypothesis, global P2X7 knockout had no impact on in vivo renal hemodynamics. Our study does not indicate a major role for P2X7 receptor activation in renal vascular injury.

Exploring the causal role of immune cells in cerebral aneurysm through single-cell transcriptomics and Mendelian randomization analysis.

Cerebral aneurysm (CA) represents a significant clinical challenge, characterized by pathological dilation of cerebral arteries. Recent evidence underscores the crucial involvement of immune cells in CA pathogenesis. This study aims to explore the complex interplay between immune cells and CA formation. We analyzed single-cell RNA sequencing data from the GSE193533 dataset, focusing on unruptured CA and their controls. Comprehensive cell-type identification and pseudo-time trajectory analyses were conducted to delineate the dynamic shifts in immune cell populations. Additionally, a two-sample Mendelian randomization (MR) approach was employed to investigate the causal influence of various immunophenotypes on CA susceptibility and the reciprocal effect of CA formation on immune phenotypes. Single-cell transcriptomic analysis revealed a progressive loss of vascular smooth muscle cells (VSMCs) and an increase in monocytes/macrophages (Mo/MΦ) and other immune cells, signifying a shift from a structural to an inflammatory milieu in CA evolution. MR analysis identified some vital immunophenotypes, such as CD64 on CD14+ CD16+ monocytes (OR: 1.236, 95% CI: 1.064-1.435, P = 0.006), as potential risk factors for CA development, while others, like CD28- CD8br %CD8br (OR: 0.883, 95% CI: 0.789-0.988, P = 0.030), appeared protective. Reverse MR analysis demonstrated that CA formation could modulate specific immunophenotypic expressions, highlighting a complex bidirectional interaction between CA pathology and immune response. This study underscores the pivotal role of immune cells in this process through the integration of single-cell transcriptomics with MR analysis, offering a comprehensive perspective on CA pathogenesis, and potentially guiding future therapeutic strategies targeting specific immune pathways.

Increased diameter and stiffness of elastic but not muscular arteries in men with abdominal aortic aneurysm.

It has been proposed that formation of abdominal aortic aneurysm (AAA) is part of a systemic arterial dilatative disease. However, arteries in the upper extremities are scarcely studied and it remains unclear whether both muscular and elastic arteries are affected by the proposed systemic arterial dilatation. The aim of this study was to investigate the diameter and stiffness of muscular and elastic arteries in arterial branches originating from the aortic arch. Twenty-six men with AAA (69 ± 4 yr) and 57 men without AAA (70 ± 5 yr) were included in the study. Ultrasound was used to examine the distal and proximal brachial artery, axillary artery, and common carotid artery (CCA), and measurement of diameter and diameter change was performed with wall-tracking software. Blood pressure measurements were used to calculate local arterial wall stiffness indices. The AAA cohort presented larger arterial diameters in the CCA and axillary artery after adjustment for body surface area (P = 0.002, respectively), whereas the brachial artery diameters were unchanged. Indices of increased stiffness in CCA (e.g., lower distensibility, P = 0.003) were seen in subjects with AAA after adjustments for body mass index and mean arterial blood pressure. This study supports the theory of a systemic arterial dilating diathesis in peripheral elastic, but not in muscular, arteries. Peripheral elastic arteries also exhibited increased stiffness, in analogy with findings in the aorta in AAA.NEW & NOTEWORTHY We present data partially supporting the notion of abdominal aortic aneurysm being a systemic vascular disease with focal manifestation in the abdominal aorta, from two well-defined groups recruited from a regional screening program. We show that elastic arteries distal from the aorta exhibit vascular alterations without aneurysmal formation in subjects with AAA compared with controls while muscular arteries seem unaffected.

P142 Effect of Atorvastatin on vascular endothelial function in early Systemic Sclerosis: An open label Randomized Controlled trial

Abstract Background/Aims Systemic Sclerosis (SSc) is driven by early endothelial dysfunction, leading to loss of endothelium-dependent vasodilatation. This predisposes to increased stiffness of large arteries. Prospective studies have found a conflicting role of statins in improving vascular function in established SSc. We undertook this study to explore if statins influence endothelium dependent vasodilation in early SSc Methods In this single center open label randomized controlled trial between July 2021 to January 2022, SSc patients (ACR-EULAR 2013) between 18-65 years, with duration &amp;lt; 3 years from the first non-Raynaud’s symptom were included. Those with complicated Raynaud’s, overlap syndromes and cardiovascular comorbidities were excluded. Participants were randomized into statin (atorvastatin 40 mg/day/A40) or no -statin arm. Both groups received stable doses of immunosuppression, during the study period. The primary outcome of flow-mediated dilation (FMD %) of brachial artery, measured by single assessor and secondary outcomes of common carotid intima medial thickness (CIMT), modified Rodnan Skin score (mRSS), Raynaud’s visual analogue scale (RayVAS:0-10), hs CRP, von Willebrand factor and oxidized low-density lipoproteins were measured at baseline and 16 weeks. All patients provided written informed consent; study protocol was approved by IEC(JIP/IEC/2020/026). Considering a change in FMD of 1% between arms as clinically meaningful, sample size was calculated to be 144. Analysis was performed using SPSS v.19.CTRI registration no: REF/2020/07/03495 Results Total 71 eligible patients were randomized into statin(n = 36) and no-statin(n = 35) arms. Baseline parameters were comparable between arms. Baseline mRSS was 14.25. On per-protocol analysis of statin (n = 28) and no-statin (n = 32) arms, there was no significant difference in FMD either at baseline or at 16 weeks (table 1). At week 16, basal brachial artery diameter increased (p = 0.008) in statin arm. Ray VAS scores improved in the statin arm,not achieving significance(p = 0.15). An increase in mRSS from 14 to 16 was noted in no-statin arm , whereas it remained stable in the statin arm (14.5). Secondary endpoints were not met. No adverse events were noted. Conclusion In early SSc, atorvastatin 40 mg/day, added to background immunosuppression, failed to improve endothelial function, assessed using brachial FMD, at 16 weeks. Stabilization of skin tightening was noted in the statin arm. Disclosure A.C. Das: None. M.M. Thabah: None. C. Mariaselvam: None. R. Vijayan: None. A. Anantharaj: None. V. Negi: None.

Characteristics of the course of multisystem inflammatory syndrome associated with COVID-19 in children according to the observations of the Kyiv City Children’s Clinical Hospital 2

Background. In the context of coronavirus diseases 2019 (COVID-19) pandemic associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a significant number of cases resembling Kawasaki disease in children have been reported worldwide and eventually termed “multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2”. Objective: to compare the clinical presentation, laboratory fin­dings, and instrumental examination data in children with Kawasaki-like MIS-C phenotype and MIS-C with a shock phenotype with cases, which met the US Centers for Disease Control and Prevention criteria. Materials and methods. The article presents the results of a retrospective analysis of the disease histories in 20 children aged 2.5 to 16 years with a Kawasaki-like MIS-C phenotype and with MIS-C with a shock phenotype associated with SARS-CoV-2 infection who were hospitalized in the MNPE “Kyiv City Children’s Clinical Hospital 2” in 2002–2021. Results. Patients were divided into 2 groups according to symptoms and pathological conditions. Group I included children with clinical signs similar to the Kawasaki disease (n = 8). They were classified as those with Kawasaki-like MIS-C phenotype. Complications such as coronary artery dilatations and aneurysms occurred only in this group. Group II consisted of patients (n = 12) who were classified as those with MIS-C with a shock phenotype. Children in this group had a higher number of involved organ systems, were more likely to have shock, pleuritis, peritonitis, and a higher prevalence of abdominal pain. Furthermore, they exhibited elevated levels of leukocytes and neutrophils (p = 0.043; p = 0.047), along with a higher neutrophil-to-lymphocyte ratio (p = 0.05), compared to the patients with Kawasaki-like phenotype. Conclusions. Our results suggest that multisystem inflammatory syndrome associated with SARS-CoV-2 in children is characterized by a wide range of clinical, laboratory and instrumental signs. Moreover, our findings highlight that children with features that correspond to MIS-C with a shock phenotype tend to have a more severe course of the disease and a higher rate of complications.

Stroke Events and Risk Factors in Older Patients with Moyamoya Disease

We aimed to comprehensively analyze the epidemiology, natural history, stroke events and their risk factors, and the RNF213 p.Arg4810Lys variant in older patients with moyamoya disease (MMD). We enrolled patients with MMD followed-up at our hospital between 2000 and 2023. Those who developed MMD at age ≥60years or were diagnosed at a younger age and followed-up after age 60years were included. Baseline characteristics, onset type, radiologic features, and RNF213 p.Arg4810Lys variant status were investigated. Among 56 patients with 100 affected hemispheres, 62 were asymptomatic, 26 experienced ischemic onset, and 12 had hemorrhagic onset. A higher incidence of anterior choroidal artery (AchA) dilatation and lower proportion of favorable modified Rankin scale scores were detected in hemorrhagic onset, whereas greater prevalence of bypass surgery in ischemic onset. Of 76 asymptomatic hemispheres at the age of 60years, subsequent stroke events occurred in 10 hemispheres, comprising 8 hemorrhages and 2 ischemias. Risk factors for de novo hemorrhage in asymptomatic hemispheres included AchA dilatation and choroidal anastomosis. Comparison of the RNF213 p.Arg4810Lys variant status showed no significant differences in baseline characteristics, onset types, or imaging findings, except for a higher percentage of patients in the GA group with a family history of MMD. Hemorrhagic events were the most prevalent and prognostically deteriorating factors in older patients with MMD aged ≥60years. AchA dilatation and choroidal anastomosis were predictors of de novo hemorrhage in asymptomatic nonsurgical hemispheres in older patients with MMD.

Hepatic artery diameter predicts bleeding risk after gastroesophageal varices treatment: a contrast-enhanced CT study.

Portal hypertension leads to hepatic artery dilatation and a higher risk of bleeding. We tried to identify the bleeding risk after gastroesophageal varices (GOV) treatment using hepatic artery diameter of contrast-enhanced CT. Retrospective retrieval of 258 patients with cirrhosis who underwent contrast-enhanced CT from January 2022 to May 2023 and endoscopy within one month thereafter at Hainan Affiliated Hospital of Hainan Medical University. Cirrhotic patients before GOV treatment were used as the test cohort (n = 199), and cirrhotic patients after GOV treatment were used as the validation cohort (n = 59). The grading and bleeding risk was classified according to the endoscopic findings. Arterial-phase images of contrast-enhanced CT were used for coronal reconstruction, and the midpoint diameter of the hepatic artery was measured on coronal images. The optimal cutoff value for identifying bleeding risk was analyzed and calculated in the test cohort, and its diagnostic performance was evaluated in the validation cohort. In the test cohort, hepatic artery diameters were significantly higher in high-risk GOV than in low-risk GOV [4.69 (4.31, 5.56) vs. 3.10 (2.59, 3.77), P < 0.001]. With a hepatic artery diameter cutoff value of 4.06mm, the optimal area under the operating characteristic curve was 0.940 (95% confidence interval: 0.908-0.972), with a sensitivity of 0.887, a specificity of 0.892, a positive predictive value of 0.904, and a negative predictive value of 0.874 for identifying bleeding risk in the test cohort, while in the validation cohort, the sensitivity was 0.885, specificity was 0.939, positive predictive value was 0.920, and negative predictive value was 0.912. Hepatic artery diameter has high diagnostic performance in identifying bleeding risk after GOV treatment.

Utilizing Digital Thermal Monitoring (DTM) to Measure Reactive Hyperemia of Type 1 Diabetes Mellitus on Cardiovascular Endothelial Function

The role of type 1 diabetes mellitus (T1DM) on the female cardiovascular system remains largely a mystery. However, it is widely accepted that insulin plays a role in cardiovascular protection. Hemoglobin A1C levels allow for further understanding of glucose impact upon endothelium and endothelial function in young females currently utilizing continuous glucose monitoring (CGM) along with insulin therapy. Flow-mediated dilation provides images of the dilation of the brachial artery under shear stress. The control group, those without a diagnosis of T1DM, are expected to have lower levels of hemoglobin A1C. The experimental group, women with T1DM, experienced significantly higher hemoglobin A1C levels and along with vascular reactivity index (VRI) scores than the control group. This finding has future influences in female cardiovascular health, protection of endothelium, and the wider debate over the influence T1DM and tighter controls of glucose regulation have on endothelial health.

Dilation of Pregnant Rat Uterine Arteries with Phenols from Extra Virgin Olive Oil Is Endothelium-Dependent and Involves Calcium and Potassium Channels.

During pregnancy, uterine vasculature undergoes significant circumferential growth to increase uterine blood flow, vital for the growing feto-placental unit. However, this process is often compromised in conditions like maternal high blood pressure, particularly in preeclampsia (PE), leading to fetal growth impairment. Currently, there is no cure for PE, partly due to the adverse effects of anti-hypertensive drugs on maternal and fetal health. This study aimed to investigate the vasodilator effect of extra virgin olive oil (EVOO) phenols on the reproductive vasculature, potentially benefiting both mother and fetus. Isolated uterine arteries (UAs) from pregnant rats were tested with EVOO phenols in a pressurized myograph. To elucidate the underlying mechanisms, additional experiments were conducted with specific inhibitors: L-NAME/L-NNA (10-4 M) for nitric oxide synthases, ODQ (10-5 M) for guanylate cyclase, Verapamil (10-5 M) for the L-type calcium channel, Ryanodine (10-5 M) + 2-APB (3 × 10-5 M) for ryanodine and the inositol triphosphate receptors, respectively, and Paxilline (10-5 M) for the large-conductance calcium-activated potassium channel. The results indicated that EVOO-phenols activate Ca2+ signaling pathways, generating nitric oxide, inducing vasodilation via cGMP and BKCa2+ signals in smooth muscle cells. This study suggests the potential use of EVOO phenols to prevent utero-placental blood flow restriction, offering a promising avenue for managing PE.

357 Effects of Dietary Nitrate Supplementation on Vascular Function in Individuals with Prediabetes

OBJECTIVES/GOALS: Impaired vascular function, a subclinical marker of cardiovascular disease, has been identified in prediabetes. Dietary nitrate supplementation has been shown to improve vascular function. However, this has not been studied in prediabetes. The purpose was to determine the effects of dietary nitrate on vascular function in prediabetes. METHODS/STUDY POPULATION: Five individuals with prediabetes (4 men, 1 woman; 55 ± 17 yr; HbA1c = 5.8 ± 0.2) participated in a double-blind, placebo-controlled, repeated measures study. Participants were randomly assigned to a 3-day nitrate supplementation (nitrate-rich beetroot juice, 12.9 mmol, 140 mL), or a placebo supplementation (nitrate-depleted beetroot juice, 0.05 mmol, 140 mL). Following supplementation, participants reported to the lab for measures of vascular function in the lower limb. Doppler ultrasonography was used to measure flow-mediated dilation (FMD) and post-occlusive reactive hyperemia (RH) of the superficial femoral artery in response to a 5-min bout of leg ischemia. RESULTS/ANTICIPATED RESULTS: FMD did not differ between the nitrate-rich (2.87 ± 2.01%) and placebo (2.24 ± 1.69%) conditions (p = 0.48; d = 0.35). Furthermore, peak RH did not differ between the nitrate-rich (1503 ± 443 ml/min) and placebo (1762 ± 414 ml/min) conditions (p = 0.36; d = 0.46). DISCUSSION/SIGNIFICANCE: These preliminary results suggest that dietary nitrate supplementation in the form of beetroot juice does not improve vascular function in individuals with prediabetes.

Left ventricular unloading in patients supported with veno-arterial extra corporeal membrane oxygenation; an international EuroELSO survey.

Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) improves end-organ perfusion in cardiogenic shock but may increase afterload, which can limit cardiac recovery. Left ventricular (LV) unloading strategies may aid cardiac recovery and prevent complications of increased afterload. However, there is no consensus on when and which unloading strategy should be used. An online survey was distributed worldwide via the EuroELSO newsletter mailing list to describe contemporary international practice and evaluate heterogeneity in strategies for LV unloading. Of 192 respondents from 43 countries, 53% routinely use mechanical LV unloading, to promote ventricular recovery and/or to prevent complications. Of those that do not routinely unload, 65% cited risk of complications as the reason. The most common indications for unplanned unloading were reduced arterial line pulsatility (68%), pulmonary edema (64%) and LV dilatation (50%). An intra-aortic balloon pump was the most frequently used device for unloading followed by percutaneous left ventricular assist devices. Echocardiography was the most frequently used method to monitor the response to unloading. Significant variation exists with respect to international practice of ventricular unloading. Further research is required that compares the efficacy of different unloading strategies and a randomized comparison of routine mechanical unloading versus unplanned unloading.