Arterial Wall Thickness Research Articles

FSI modeling on the effect of artery-aneurysm thickness and coil embolization in patient cases

Background and objectiveThe attainment of a methodology to simulate the hemodynamic in patient-specific cerebral vessels with aneurysms is still a challenge. The novelty of this work is focused on the effect of coil embolization in a realistic cerebral aneurysm, according to the vessel wall thickness and aneurysm thickness, through transient FSI simulations. MethodsThe quality of the mesh for simulations was checked with a specific mesh convergence study; and the numerical methodology was validated using numerical research data of the literature. The model was implemented in ANSYS® software. The total deformation and equivalent stress evolution in the studied cases, before and after coil embolization, were compared. More than 20 different models were employed due to different arterial wall thickness and aneurysm wall thickness combinations. ResultsThe obtained results have showed that deformation and stress values are highly influenced with the sac thickness. The thinner sac aneurysm thickness is, the greater deformation and stress are. The results after coil embolization process have highlighted that considering typical values of arterial wall thickness and aneurysm thickness 0.3 mm and 0.15 mm respectively, a deformation reduction around 50% and a stress reduction around 70% can be achieved. ConclusionsThe proposed methodology is a step forward in the personalized medicine, quantifying the aneurysm rupture risk reduction, and helping the medical team in the preoperative planning, or to deciding the optimal treatment.

The Effect of Diltiazem on Microcirculation of Transplanted Tissue Flaps: Experimental Study on Rabbits.

BACKGROUNDThe aim of the presented study was to investigate the inhibitory effect of diltiazem on the microcirculation of the tissue flaps created in the delay phenomenon applied rabbits.METHODSThe experiment was performed in Central Research Laboratory of Azerbaijan Medical University, Baku, Azerbaijan in 2018. Ischemia model on the flaps were formed in 30 rabbits for experiment. The subjects were divided into three groups: I (control) group - consists of 10 rabbits who underwent ischemia model, but no medication had been used during the duration of the experiment; II (comparative) group - consists of 10 rabbits who underwent ischemia model, and during 14 d, with a daily dose of 60 mсg nitroglycerin had been applied; III (main) group - consists of 10 rabbits who underwent ischemia model, and during 14 d, with a daily dose of 45 mg diltiazem had been applied.RESULTSThere was statistically significant difference between the control and the main groups when comparing the mean values of endothelial hyperplasia (P=0.001). However, we found a statistically significant difference when compared the mean values of the arterial vessel wall thickening in the main and the control groups (P=0.022); and the mean values of thrombosis in the main and the comparative groups (P=0.001).CONCLUSIONWith prescription of diltiazem, endothelial hyperplasia on microcirculatory system, the thickening of arterial vessel walls, the thrombosis in vessel’s passage was rarely seen by statistical difference. The main achievement of our study was to discover the correlation between diltiazem and endothelial hyperplasia.

Mechanisms for the Age‐Related Differences in Cerebral Artery Endothelial Function After Exposure to Elevated Pulse Pressure

Greater large artery stiffness is correlated with increased cerebrovascular dysfunction and damage. One possible mechanism for this correlation is increased pulse pressure in cerebral resistance arteries, a result of less dampening of pulse pressure by the large arteries, leading to reduced cerebral artery endothelial function. Old age is associated with increases in large artery stiffness and cerebrovascular impairment; however, the effect of age on the response to elevated pulse pressure in cerebral arteries is unclear. Thus, we hypothesized that cerebral resistance arteries exhibit an age-related decline in endothelial function following exposure to pulsatile pressure. In young (n=41, 5-10 mo.) and old (n=26, 25-30 mo.) male C57BL6 mice, we measured cerebrovascular function by the ex vivo endothelium-dependent dilation (EDD) to acetylcholine (ACh) in isolated posterior cerebral arteries following exposure to static pressure (50 mmHg), low pulse pressure (50-75 mmHg), or high pulse pressure (37.5-87.5 mmHg)(400bpm). We also determined the effects of nitric oxide synthase inhibition (L-NAME) and decomposition of hydrogen peroxide (PEG-catalase) on the response to ACh. We measured endothelium-independent dilation (EID) by the dose response to sodium nitroprusside. We also measured posterior cerebral artery wall thickness in young and old mice using histological analysis. Compared with young mice, cerebral arteries from old mice had a 37.3% lower maximal EDD during exposure to static pressure (p<0.001), but EID did not differ with age (p=0.86). Exposure to low pulse pressure did not affect maximal EDD for either young or old cerebral arteries (p>0.05). In young cerebral arteries, maximal EDD was 43.9% lower after exposure to high pulse pressure compared with static pressure (p<0.005); however, high pulse pressure had no effect on maximal EDD in old cerebral arteries (p=0.39). Addition of L-NAME reduced maximal EDD in both old (p=0.001) and young (p<0.001) cerebral arteries during all pressure conditions, such that maximal EDD was no longer different between groups (p>0.05). In young cerebral arteries, the presence of PEG-catalase led to a lower maximal EDD in the static pressure (p=0.045) and low pulse pressure (p=0.001) conditions and trended towards greater maximal EDD in the high pulse pressure condition (p=0.08). Cerebral arteries from old mice had a 22% greater wall thickness compared with cerebral arteries from young mice (p=0.047). In conclusion, these results suggest high pulse pressure impairs endothelial function in cerebral resistance arteries from young mice, and this impairment results from lowered bioavailability of the products of nitric oxide synthase and reduced contribution by hydrogen peroxide to vasodilation. Contrary to our hypothesis, cerebral arteries from old mice were protected from the deleterious effects of high pulse pressure, perhaps as a result of arterial remodeling in response to chronic exposure to higher pulse pressure in vivo.

Subclinical atherosclerosis in patients with relapsing-remitting multiple sclerosis.

Multiple sclerosis is an inflammatory disorder of the central nervous system. Inflammation may create high susceptibility to subclinical atherosclerosis. The purpose of this study was to compare subclinical atherosclerosis and the role of inflammatory cytokines between the group of patients with relapsing-remitting multiple sclerosis (RRMS) and healthy controls matched for age and sex. The study group consisted of 112non-diabetic and non-hypertensive RRMS patients treated with disease modifying drugs (DMD) and the control group was composed of 51healthy subjects. The common carotid artery (CCA) intima media thickness (IMT) was investigated. Serum levels of risk factors for atherosclerosis and inflammatory cytokines were also determined. The mean CCA IMT (0.572 ± 0.131 mm vs. 0.571 ± 0.114 mm) did not differ (p > 0.05) between patients and controls. The RRMS patients' CCA IMT was significantly correlated with serum interleukin6 (IL-6) (p = 0.027), high-sensitivity C-reactive protein (hs-CRP) (p = 0.027), cystatinC (p < 0.0005), glucose (p = 0.031), cholesterol (p = 0.008), LDL (p = 0.021), erythrocyte sedimentation rate (p = 0.001) and triglyceride (p = 0.018) level. We fitted generalized linear models in order to assess the relationship between CCA IMT and IL‑6 with adjustment for sex and age. The obtained results showed that adjusted for age (p < 0.001) and sex (p = 0.048) IL‑6 serum levels statistically significantly (p = 0.009) predict CCA IMT only in the RRMS group. The findings of the present study suggest that when treated with DMD RRMS might not be an independent risk factor for early atherosclerosis presenting with arterial wall thickening; however, the results suggest a significant association of IL‑6 serum levels with CCA IMT only in the RRMS group.

P204 An evaluation of a daily fast-track diagnostic ultrasound service for patients with suspected new onset giant cell arteritis during the COVID-19 pandemic

Background/Aims COVID-19 has reinforced the necessity for a faster and more accurate diagnostic pathway for suspected giant cell arteritis (GCA) patients so that unnecessary use of glucocorticoids can be avoided/minimised. During the COVID-19 pandemic, we replaced a twice weekly service with a 5 day per week ultrasound-based fast-track pathway within a secondary/tertiary hospital. The aim was to determine the impact of a more frequent diagnostic service for GCA, based on rapid access to ultrasound and clinical evaluation on the diagnostic certainty in evaluating patients with newly suspected GCA. Methods We reviewed records from patients referred between November 2019 to July 2020, comparing those seen during 17 weeks ‘pre-COVID’, using the twice weekly service, with patients seen during 17 weeks of a 5 day per week service, termed ‘intra-COVID’. All patients underwent clinical evaluation and an eight-site ultrasound of temporal and axillary arteries. Those with hypoechoic, non-compressible peri-luminal arterial wall-thickening (or halo sign) were considered ultrasound ‘positive’. Results We audited 139 patients with suspected GCA (63 pre-COVID period vs 76 intra-COVID). A clinical diagnosis of GCA was made in 33.3% pre-COVID and 42% intra-COVID (p = 0.289). Ultrasound sensitivity improved from 38.1% to 68.6% (p < 0.0001), whilst specificity remained unchanged (100%, p < 0.0001) for both periods. The proportion of patients seen within seven days of referral improved by 61.6% (p < 0.0001), from 31.7% (pre-COVID) to 93.3% (intra-COVID). The median number of days from referral to assessment fell over four-fold, from 12.5 (interquartile range [IQR]=8.25) to 3 (IQR=3.5) respectively. Median number of days of steroid exposure fell over seven-fold from 15 days (IQR=11.25) pre-COVID to 2 days (IQR=5) intra-COVID. Similar proportions in both periods were empirically commenced on steroids prior to assessment (71% vs 68% respectively, p = 0.700). Mean number of ‘halos’ increased from 0.25 (standard deviation [SD]1.19) pre-COVID to 3.05 (SD = 1.82) intra-COVID. The was no significant difference in the number of GCA visual complications (p = 0.894). Ultrasound positivity was associated with fewer days of steroid exposure: the median number of days on steroids in negative versus positive scans was 16 and 5.5 (pre-COVID); compared to 2.5 and 1 days (intra-COVID). The proportion of patients without GCA who were empirically commenced on steroids reduced from 71.4% to 56.8% (pre-COVID vs intra-COVID, p = 0.158) and median days steroid exposure reduced from 9.5 (IQR=17.5) to 1 (IQR=5), respectively. Conclusion A regular, daily ultrasound service for diagnosing suspected GCA significantly improved diagnostic accuracy and reduced unnecessary steroid exposure in patients who did not have GCA. The sensitivity of ultrasound improved by 30.5% and the delay from steroid exposure to diagnosis was reduced by 76%. An ultrasound-based daily fast-track service significantly improved the diagnostic certainty of suspected GCA, especially during the COVID-19 pandemic when availability of temporal artery biopsy was very limited. Disclosure J.P. White: None. G. Sallemi: None. B. Dhungana: None. S. Dubey: None. R.A. Luqmani: None.

Ghrelin Protects Lipopolysaccharide-Induced Acute Lung Injury Rats against Pulmonary Vascular Dysfunction by Inhibiting Inflammation

Objective. To determine the effect and mechanism of the anti-inflammatory agent ghrelin on pulmonary vascular dysfunction (PVD) in lipopolysaccharide- (LPS-) induced acute lung injury (ALI) rat models. Methods. Thirty-two adult male Sprague Dawley rats (n = 16/group) were randomly divided into ghrelin and saline groups, wherein ghrelin (10 nmol/kg) or saline was subcutaneously administered. After 30 min, eight rats from each group were randomly selected, and LPS (5 mg/kg) or saline was administered by intratracheal instillation to induce ALI. Four hours after establishing the ALI rat model, the mean pulmonary arterial pressure (mPAP), mean right ventricular systolic pressure (RVSP), levels of proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the bronchoalveolar lavage fluid (BALF), BALF cell count, wet-to-dry (W/D) lung weight ratios, and myeloperoxidase (MPO) activity in lung tissue for all four groups (ghrelin, ghrelin + ALI, saline, and saline + ALI) were measured. Immunohistochemical staining to detect alpha-smooth muscle actin (α-SMA) and proliferating cell nuclear antigen (PCNA) expression was performed to assess the intrapulmonary arterial wall thickness and the proliferation of smooth muscle cells, respectively. Results. The ghrelin-pretreated ALI rats showed lower mPAP, RVSP, PCNA expression, MPO activity, W/D lung weight ratio, TNF-α and IL-6 levels, and BALF cell count than the saline-pretreated ALI rats, but ghrelin had no effect on the intrapulmonary arterial wall thickness of ALI rats. Conclusion. Our results confirmed the association between inflammation and PVD in ALI and suggested that the suppression of inflammation by ghrelin pretreatment could protect LPS-induced ALI rats against PVD.

Delayed treatment with Endostatin displays a protective role against pulmonary hypertension by targeting VEGF pathway.

Endostatin (ES) is an endogenous angiogenesis inhibitor. It is confirmed that ES has antitumor effects and plays a crucial part in regulating vascular smooth cells' proliferation. However, ES's effect on pulmonary hypertension (PH) is unclear. We aimed to determine the effect of ES on PH's pathogenesis. PH was induced by pneumonectomy plus monocrotaline (MCT) injection, as indicated with significantly increased pulmonary arterial pressure and vascular wall thickness. Immunohistochemical analysis showed that under physiological conditions, ES localized in endothelial cells (ECs) and spread to the muscular vascular layers in PH rats. ES was transfected into the lungs of rats intratracheally 2 weeks after MCT injection. Consequently, ES not only reduced elevated VEGF's expression but also reversed pulmonary artery remodeling. Eventually, ES improved elevated right ventricular (RV) mean pressure and RV hypertrophy. The administration of ES may be a new treatment for PH and PA remodeling, associating with the down-regulation of VEGF production.

Association between popliteal artery wall thickness and structural progression in individuals with symptomatic knee osteoarthritis

Purpose: Osteoarthritis is the most prevalent chronic joint disorder with multifactorial aetiologies. There has been evidence for the involvement of vascular pathology in the progression and development of knee osteoarthritis. Increased popliteal artery wall thickness has been shown to be a risk factor for cardiovascular disease, being used as a surrogate marker of atherosclerosis. Previous studies have shown associations between increased popliteal artery wall thickness and adverse knee structural changes in community-based adults without clinical knee osteoarthritis.

Fasudil Dichloroacetate Alleviates SU5416/Hypoxia-Induced Pulmonary Arterial Hypertension by Ameliorating Dysfunction of Pulmonary Arterial Smooth Muscle Cells.

BackgroundPulmonary arterial hypertension (PAH) is an incurable disease that urgently needs therapeutic approaches. Based on the therapeutic effects of fasudil and dichloroacetate (DCA) on PAH, we aimed to explore the effects and potential mechanism of a new salt, fasudil dichloroacetate (FDCA), in a SU5416 plus hypoxia (SuHx)-induced rat model of PAH.MethodsThe rat model of PAH was established by a single subcutaneous injection of SU5416 (20 mg/kg) followed by hypoxia (10% O2) exposure for 3 weeks. FDCA (15, 45, or 135 mg/kg i.g. daily) or the positive control, bosentan (100 mg/kg i.g. daily), were administered from the first day after SU5416 injection. After 3-week hypoxia, hemodynamic parameters, and histological changes of the pulmonary arterial vessels and right ventricle (RV) were assessed. Additionally, in vitro, the effects of FDCA (50 μM), compared with equimolar doses of fasudil, DCA, or fasudil+DCA, on the proliferation, migration, and contraction of human pulmonary arterial smooth muscle cell (PASMC) under hypoxia (1% O2) were evaluated.ResultsFDCA dose-dependently attenuated SuHx-induced PAH, with significant reductions in RV systolic pressure, pulmonary artery wall thickness, pulmonary vessel muscularization, perivascular fibrosis, as well as RV hypertrophy and fibrosis. In vitro, FDCA inhibited hypoxia-induced PASMC proliferation, migration, and contraction to a greater degree than fasudil or DCA alone by restoring mitochondrial function, reducing intracellular Ca2+, and inhibiting calcium/calmodulin-dependent kinase (Ca2+/CaMK) activity as well as Rho-kinase activity.ConclusionFDCA ameliorates hypoxia-induced PASMC dysfunction by inhibiting both Ca2+/CaMK and Rho-kinase signaling pathways, as well as maintaining mitochondrial homeostasis, thus alleviating SuHx-induced PAH.

Endothelial epidermal growth factor receptor is of minor importance for vascular and renal function and obesity-induced dysfunction in mice

Vascular EGF receptors (EGFR) influence function and structure of arterial vessels. In genetic mouse models we described the role of vascular smooth muscle (VSMC) EGFR for proper physiological function and structure as well as for pathophysiological alterations by obesity or angiotensin II. As the importance of endothelial (EC) EGFR in vivo is unknown, we analyzed the impact of EC-EGFR knockout in a conditional mouse model on vascular and renal function under control condition as well as in obesity and in comparison to VSMC-KO. Heart and lung weight, blood pressure and aortic transcriptome (determined by RNA-seq) were not affected by EC-EGFR-KO. Aortic reactivity to α1-adrenergic stimulation was not affected by EC-EGFR-KO contrary to VSMC-EGFR-KO. Endothelial-induced relaxation was reduced in abdominal aorta of EC-EGFR-KO animals, whereas it was enhanced in VSMC-EGFR-KO animals. Mesenteric arteries of EC-EGFR-KO animals showed enhanced sensitivity to α1-adrenergic stimulation, whereas endothelial-induced relaxation and vessel morphology were not affected. Renal weight, histomorphology, function (albumin excretion, serum creatinine, fractional water excretion) or transcriptome were not affected by EC-EGFR-KO, likewise in VSMC-EGFR-KO. High fat diet (HFD) over 18 weeks induced arterial wall thickening, renal weight increase, creatininemia, renal and aortic transcriptome alterations with a similar pattern in EC-EGFR-WT and EC-EGFR-KO animals by contrast to the previously reported impact of VSMC-EGFR-KO. HFD induced endothelial dysfunction in abdominal aortae of EC-EGFR-WT, which was not additive to the EC-EGFR-KO-induced endothelial dysfunction. As shown before, VSMC-EGFR-KO prevented HFD-induced endothelial dysfunction. HFD-induced albuminuria was less pronounced in EC-EGFR-KO animals and abrogated in VSMC-EGFR-KO animals. Our results indicate that EC-EGFR, in comparison to VSMC-EGFR, is of minor and opposite importance for basal renovascular function as well as for high fat diet-induced vascular remodeling and renal end organ damage.

Correlations between Retinal Arterial Morphometric Parameters and Neurodegeneration in Patients with Type 2 Diabetes Mellitus with No or Mild Diabetic Retinopathy.

Background and Objectives: In patients with diabetes mellitus (DM), the neural retina is starting to degenerate before the development of vascular lesions. Our purpose was to investigate the correlation between the retinal arterial morphometric parameters and structural neurodegeneration in patients with type 2 DM with no or mild diabetic retinopathy (DR). Materials and Methods: This is a prospective study including 53 eyes of patients with type 2 DM and 32 eyes of healthy controls. Based on SD-OCT (spectral domain—optical coherence tomography) images, using a micro-densitometry method, we measured the outer and luminal diameter of retinal arteries and calculated the AWT (arterial wall thickness), WLR (wall-to-lumen ratio), and WCSA (wall cross-sectional area). GCL (ganglion cell layer) and RNFL (retinal nerve fiber layer) thickness were analyzed in correlation with the retinal arterial morphometric parameters mentioned above. Results: GCL was thinner in the inner quadrants in the NDR (no DR) group compared to controls (p < 0.05). RAOD (retinal artery outer diameter), RALD (retinal artery lumen diameter), AWT, WLR, and WCSA were similar between groups. A regression model considering age, gender, duration of DM, and HbA1C was carried out. Central GCL thickness was correlated positively with RAOD (coefficient 0.360 per µm, p = 0.011), RALD (coefficient 0.283 per µm, p = 0.050), AWT (coefficient 0.304 per µm, p = 0.029), and WCSA (coefficient 3.90 per µm, p = 0.005). Duration of DM was positively correlated with WCSA (coefficient 0.311 per one year duration of diabetes, p = 0.043). Conclusions: Significant GCL thinning in the inner quadrants preceded the morphological retinal arterial morphometric changes, supporting the neurodegeneration as primary pathogenic mechanism in DR.

Evaluating renal arterial wall by non-enhanced 2D and 3D free-breathing black-blood techniques: Initial experience

ObjectivesTo evaluate the feasibility and reproducibility of 2D and 3D black-blood sequences in measuring morphology of renal arterial wall. MethodsThe 2D and 3D imaging sequences used variable-refocusing-flip-angle and constant-low-refocusing-flip-angle turbo spin echo (TSE) readout respectively, with delicately selected black-blood scheme and respiratory motion trigger for free-breathing imaging. Fourteen healthy subjects and three patients with Takayasu arteritis underwent renal artery wall imaging with 3D double inversion recovery (DIR) TSE and 2D Variable Flip Angle-TSE (VFA-TSE) black-blood sequences at 3.0 T. Four healthy subjects were randomly selected for scan-rescan reproducibility experiments. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and morphology of arterial wall were measured and compared using paired-t-test or Wilcoxon signed-rank test between 2D and 3D sequences. The inter-observer, intra-observer and scan-rescan agreements of above measurements were determined using intraclass correlation coefficient (ICC). ResultsThe 2D and 3D imaging sequences showed similar morphological measurements (lumen area, wall area, mean wall thickness and maximum wall thickness) of renal arterial wall (all P > 0.05) and excellent agreement (ICC: 0.853–0.954). Compared to 2D imaging, 3D imaging exhibited significantly lower SNRlumen (P < 0.01) and SNRwall (P = 0.037), similar contrast-to-noise ratio (CNR) (P = 0.285), and higher CNR efficiency (CNReff) (P < 0.01). Both 2D and 3D imaging showed good to excellent inter-observer (ICC: 0.723–0.997), intra-observer (ICC: 0.749–0.996) and scan-rescan (ICC: 0.710–0.992) reproducibility in measuring renal arterial wall morphology, SNR and CNR, respectively. ConclusionsBoth high-resolution free-breathing 2D VFA-TSE and 3D DIR TSE black-blood sequences are feasible and reproducible in high-resolution renal arterial wall imaging. The 2D imaging has high SNR, whereas 3D imaging has high imaging efficiency.

PIV Analysis of Haemodynamics Distal to the Frozen Elephant Trunk Stent Surrogate.

The Frozen Elephant Trunk (FET) stent is a hybrid endovascular device that may be implemented in the event of an aneurysm or aortic dissection of the aortic arch or superior descending aorta. A Type 1B endoleak can lead to intrasaccular flow during systole and has been identified as a known failure of the FET stent graft. The purpose was to develop in-vitro modelling techniques to enable the investigation of the known failure. A silicone aortic phantom and 3D printed surrogate stent graft were manufactured to investigate the haemodynamics of a Type 1B endoleak. Physiological pulsatile flow dynamics distal to the surrogate stent graft were investigated in-vitro using Particle Image Velocimetry (PIV). PIV captured recirculation zones and an endoleak distal to the surrogate stent graft. The endoleak was developed at the peak of systole and sustained until the onset of diastole. The endoleak was asymmetric, indicating a potential variation in the phantom artery wall thickness or stent alignment. Recirculation was identified on the posterior dorsal line during late systole. The identification of the Type 1B endoleak proved that in-vitro modelling can be used to investigate complex compliance changes and wall motions. The recirculation may indicate the potential for long term intimal layer inflammatory issues such as atherosclerosis. These results may aid future remediation techniques or stent design. Further development of the methods used in this experiment may assist with the future testing of stents prior to animal or human trial.

Gestational long-term hypoxia induces metabolomic reprogramming and phenotypic transformations in fetal sheep pulmonary arteries.

Gestational long-term hypoxia increases the risk of myriad diseases in infants including persistent pulmonary hypertension. Similar to humans, fetal lamb lung development is susceptible to long-term intrauterine hypoxia, with structural and functional changes associated with the development of pulmonary hypertension including pulmonary arterial medial wall thickening and dysregulation of arterial reactivity, which culminates in decreased right ventricular output. To further explore the mechanisms associated with hypoxia-induced aberrations in the fetal sheep lung, we examined the premise that metabolomic changes and functional phenotypic transformations occur due to intrauterine, long-term hypoxia. To address this, we performed electron microscopy, Western immunoblotting, calcium imaging, and metabolomic analyses on pulmonary arteries isolated from near-term fetal lambs that had been exposed to low- or high-altitude (3,801 m) hypoxia for the latter 110+ days of gestation. Our results demonstrate that the sarcoplasmic reticulum was swollen with high luminal width and distances to the plasma membrane in the hypoxic group. Hypoxic animals were presented with higher endoplasmic reticulum stress and suppressed calcium storage. Metabolically, hypoxia was associated with lower levels of multiple omega-3 polyunsaturated fatty acids and derived lipid mediators (e.g., eicosapentaenoic acid, docosahexaenoic acid, α-linolenic acid, 5-hydroxyeicosapentaenoic acid (5-HEPE), 12-HEPE, 15-HEPE, prostaglandin E3, and 19(20)-epoxy docosapentaenoic acid) and higher levels of some omega-6 metabolites (P < 0.02) including 15-keto prostaglandin E2 and linoleoylglycerol. Collectively, the results reveal broad evidence for long-term hypoxia-induced metabolic reprogramming and phenotypic transformations in the pulmonary arteries of fetal sheep, conditions that likely contribute to the development of persistent pulmonary hypertension.

Arterial wall thickening normalizes arterial wall tension with growth in American alligators, Alligator mississippiensis.

Arterial wall tension increases with luminal radius and arterial pressure. Hence, as body mass (Mb) increases, associated increases in radius induces larger tension. Thus, it could be predicted that high tension would increase the potential for rupture of the arterial wall. Studies on mammals have focused on systemic arteries and have shown that arterial wall thickness increases with Mb and normalizes tension. Reptiles are good models to study scaling because some species exhibit large body size range associated with growth, thus, allowing for ontogenetic comparisons. We used post hatch American alligators, Alligator mississippiensis, ranging from 0.12 to 6.80kg (~ 60-fold) to investigate how both the right aortic arch (RAo) and the left pulmonary artery (LPA) change with Mb. We tested two possibilities: (i) wall thickness increases with Mb and normalizes wall tension, such that stress (stress = tension/thickness) remains unchanged; (ii) collagen content scales with Mb and increases arterial strength. We measured heart rate and systolic and mean pressures from both systemic and pulmonary circulations in anesthetized animals. Once stabilized alligators were injected with adrenaline to induce a physiologically relevant increase in pressure. Heart rate decreased and systemic pressures increased with Mb; pulmonary pressures remained unchanged. Both the RAo and LPA were fixed under physiological hydrostatic pressures and displayed larger radius, wall tension and thickness as Mb increased, thus, stress was independent from Mb; relative collagen content was unchanged. We conclude that increased wall thickness normalizes tension and reduces the chances of arterial walls rupturing in large alligators.

Time in Range Does Not Associate With Carotid Artery Wall Thickness and Endothelial Function in Type 1 Diabetes.

Patients with Type 1 diabetes (T1D) have an increased risk of developing atherosclerosis and complications as myocardial infarction and peripheral artery disease. The thickening of the carotid wall and the brachial artery dysfunction are early and preclinical manifestations of atherosclerosis. The standard marker of care for assessment of glycemic control, glycated hemoglobin, does not associate with early atherosclerosis. We have hypothesized that the emerging metric of glycemic control, as the time spent in the target range (TIR), might be associated with carotid thickening and endothelial dysfunction. According to the hypothesis, we have designed the present research with the aim to evaluate the association between TIR collected in the short and long term and the measures of arterial morphology and function in patients with T1D. In our study, 70 patients and 35 healthy controls underwent ultrasound vascular study to measure carotid artery intima-media thickness (IMT) and brachial artery endothelial function by the flow-mediated dilation (FMD) technique. TIR was collected by a continuous glucose monitoring system for 2 weeks, 3 months, and 6 months before the vascular study. Patients with T1D showed a significantly higher carotid IMT (mean±SE, 644±19 vs. 568±29 µ; p= 0.04) and a significantly lower FMD (mean±SE, 7.6±0.4 vs. 9.8±0.6%; p=0.01) compared with control subjects. No significant relationship between IMT, FMD, and TIR collected in the short and long term emerged. Young patients with T1D have early vascular abnormalities. The percent of TIR does not correlate with preclinical atherosclerosis. This finding underlines the complexity of the interplay between diabetes and atherosclerosis.

Estimating Arterial Wall Deformations from Automatic Key-Point Detection and Matching

Assessing arterial-wall motion and deformations may reveal pathologic alterations in biomechanical properties of the parietal tissues and, thus, contribute to the detection of vascular disease onset. Ultrasound image sequences allow the observation of this motion and many methods have been developed to estimate temporal changes in artery diameter and wall thickness and to track 2-D displacements of selected points. Some methods enable the assessment of shearing or stretching within the wall, but none of them can estimate all these deformations simultaneously. The method herein proposed was devised to simultaneously estimate translation, compression, stretching and shearing of the arterial wall in ultrasound B-mode image sequences representing the carotid artery longitudinal section. Salient blob-like patterns, called key points, are automatically detected in each frame and matched between successive frames. A robust estimator based on an affine transformation model is then used to assess frame-to-frame motion explaining at best the key-point matches and to reject outliers. Realistic simulated image sequences were used to evaluate the accuracy and robustness of the method against ground truth. The method was also visually assessed on clinical image sequences, for which true deformations are unknown.

Dried mulberry fruit ameliorates cardiovascular and liver histopathological changes in high-fat diet-induced hyperlipidemic mice

Background and aimMetabolic disease encompasses most contemporary non-communicable diseases, especially cardiovascular and fatty liver disease. Mulberry fruits of Morus alba L. are a favoured food and a traditional medicine. While they are anti-atherosclerotic and reduce hyperlipidemic risk factors, studies need wider scope that include ameliorating cardiovascular and liver pathologies if they are to become clinically effective treatments. Therefore, the present study sought to show that freshly dried mulberry fruits (dMF) might counteract the metabolic/cardiovascular pathologies in mice made hyperlipidemic by high-fat diet (HF). Experimental procedureC57BL/6J mice were fed for 3 months with either: i) control diet, ii) HF, iii) HF+100 mg/kg dMF, or iv) HF+300 mg/kg dMF. Body weight gain, food intake, visceral fat accumulation, fasting blood glucose, plasma lipids, and aortic, heart, and liver histopathologies were evaluated. Adipocyte lipid accumulation, autophagy, and bile acid binding were also investigated. Results and conclusionHF increased food intake, body weight, visceral fat, plasma total cholesterol (TC) and low-density lipoprotein (LDL), TC/HDL ratio, blood glucose, aortic collagen, arterial and cardiac wall thickness, and liver lipid. Both dMF doses prevented hyperphagia, body weight gain, and visceral fat accumulation, lowered blood glucose, plasma TG and unfavourable TC/HDL and elevated plasma HDL beyond baseline. Arterial and cardiac wall hypertrophy, aortic collagen fibre accumulation and liver lipid deposition ameliorated in dMF-fed mice. Clinical trials on dMF are worthwhile but outcomes should be holistic commensurate with the constellation of disease risks. Here, dMF should supplement the switch to nutrient-rich from current energy-dense diets that are progressively crippling national health systems.

Mitochondrial DAMPs and altered mitochondrial dynamics in OxLDL burden in atherosclerosis

Atherosclerosis results in life-threatening cardiovascular pathologies, including ischemic heart disease, stroke, myocardial infarction, and peripheral arterial disease. The role of increased serum low-density lipoprotein (LDL) and resultant accumulation of oxidized-LDL (oxLDL) in atheroma formation is well established. Recent findings elucidate the significance of mitochondrial damage-associated molecular patterns (mtDAMPs) in triggering sterile inflammation in concert with oxLDL. The mtDAMPs including mitochondrial DNA (mtDNA), cytochrome C, cardiolipin, heat shock protein 60 (HSP60), mitochondrial transcription factor A (TFAM), and N-formyl peptides, are expected to possess proatherogenic roles. However, limited data are available in the literature. The mtDAMPs initiate sterile inflammation in atherosclerotic lesions via numerous signaling pathways, most of which converge to the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome. Priming the activation of the NLRP3 inflammasome, mtDAMPs promote secretion of proinflammatory cytokines, including interleukin-1β (IL-1β), implicated in atherosclerotic lesions through vascular smooth muscle and fibroblast proliferation, arterial wall thickening, and plaque formation. In this article we critically reviewed and discussed the central role of the NLRP3 inflammasome in mtDAMP-induced sterile inflammation in atherosclerosis with specific components including caspase-1, pregnane X receptor (PXR), adenosine monophosphate activated protein kinase (AMPK), protein phosphatase 2A (PP2A), thioredoxin-interacting protein (TXNIP), and downstream cytokines including IL-1β and IL-18 as potential mediators of atherosclerosis. Better understanding of the proinflammatory effects of mtDAMPs and its pathological association with oxLDL possess immense translational significance for novel therapeutic intervention.

Morphological findings in frozen non-neoplastic kidney tissues of patients with kidney cancer from large-scale multicentric studies on renal cancer

There are unexplained geographical variations in the incidence of kidney cancer with the high rates reported in Baltic countries, as well as eastern and central Europe. Having access to a large and well-annotated collection of “tumor/non-tumor” pairs of kidney cancer patients from the Czech Republic, Romania, Serbia, UK, and Russia, we aimed to analyze the morphology of non-neoplastic renal tissue in nephrectomy specimens. By applying digital pathology, we performed a microscopic examination of 1012 frozen non-neoplastic kidney tissues from patients with renal cell carcinoma. Four components of renal parenchyma were evaluated and scored for the intensity of interstitial inflammation and fibrosis, tubular atrophy, glomerulosclerosis, and arterial wall thickening, globally called chronic renal parenchymal changes. Moderate or severe changes were observed in 54 (5.3%) of patients with predominance of occurrence in Romania (OR = 2.67, CI 1.07–6.67) and Serbia (OR = 4.37, CI 1.20–15.96) in reference to those from Russia. Further adjustment for comorbidities, tumor characteristics, and stage did not change risk estimates. In multinomial regression model, relative probability of non-glomerular changes was 5.22 times higher for Romania and Serbia compared to Russia. Our findings show that the frequency of chronic renal parenchymal changes, with the predominance of chronic interstitial nephritis pattern, in kidney cancer patients varies by country, significantly more frequent in countries located in central and southeastern Europe where the incidence of kidney cancer has been reported to be moderate to high. The observed association between these pathological features and living in certain geographic areas requires a larger population-based study to confirm this association on a large scale.