Risk Factor For Vascular Disease Research Articles

Myocardin related transcription factor and galectin-3 drives lipid accumulation in human blood vessels

ObjectiveDiabetes and hypertension are important risk factors for vascular disease, including atherosclerosis. A driving factor in this process is lipid accumulation in smooth muscle cells of the vascular wall. The glucose- and mechano-sensitive transcriptional coactivator, myocardin-related transcription factor A (MRTF-A/MKL1) can promote lipid accumulation in cultured human smooth muscle cells and contribute to the formation of smooth muscle-derived foam cells. The purpose of this study was to determine if intact human blood vessels ex vivo can be used to evaluate lipid accumulation in the vascular wall, and if this process is dependent on MRTF and/or galectin-3/LGALS3. Galectin-3 is an early marker of smooth muscle transdifferentiation and a potential mediator for foam cell formation and atherosclerosis. Approach and resultsHuman mammary arteries and saphenous veins were exposed to altered cholesterol and glucose levels in an organ culture model. Accumulation of lipids, quantified by Oil Red O, was increased by cholesterol loading and elevated glucose concentrations. Pharmacological inhibition of MRTF with CCG-203971 decreased lipid accumulation, whereas adenoviral-mediated overexpression of MRTF-A had the opposite effect. Cholesterol-induced expression of galectin-3 was decreased after inhibition of MRTF. Importantly, pharmacological inhibition of galectin-3 with GB1107 reduced lipid accumulation in the vascular wall after cholesterol loading. ConclusionEx vivo organ culture of human arteries and veins can be used to evaluate lipid accumulation in the intact vascular wall, as well as adenoviral transduction and pharmacological inhibition. Although MRTF and galectin-3 may have beneficial, anti-inflammatory effects under certain circumstances, our results, which demonstrate a significant decrease in lipid accumulation, support further evaluation of MRTF- and galectin-3-inhibitors for therapeutic intervention against atherosclerotic vascular disease.

Novel Role of YAP1 in Regulating Blood Pressure and Vascular Tone

Introduction: Hypertension is a major risk factor for occlusive vascular diseases, myocardial infarction, heart failure, stroke, and chronic kidney disease. In the U.S., ~30% of adults suffer from hypertension. Merely half of the individuals with hypertension have their blood pressure under control, despite the wide range of antihypertensive medications available, indicating an urgent need for a better understanding of the underlying causes of hypertension to identify novel therapeutic strategies for its treatment and prevention. Recent genome-wide association study (GWAS) has identified an unexpected association between a loss-of-function SNP in the YAP1 gene locus and decreased blood pressure (BP). Moreover, de novo analysis of publicly available RNAseq data revealed that the vascular tissues of hypertensive mice treated with Ang-II exhibit increased YAP1 expression. Suggesting a novel role of YAP1 in blood pressure regulation. However, whether Vascular smooth muscle cell (VSMC) expressed YAP1 has a specific role in VSMC contraction and BP regulation remains completely unknown. Therefore, we hypothesized that YAP1 could play a key role in regulating blood pressure. Methodology: We have generated a novel inducible SM-specific- Yap1 Knockout ( YAP1 iKO) mouse model and employed a pharmacological inhibitor of YAP1, Verteporfin, to delineate the functional role of VSMC-expressed YAP1 in hypertension in regulating vascular tone and BP. Vascular reactivity experiments were performed using wire myography. BP was measured in ambulant mice via radiotelemetry. In vitro gain- and loss-of-function studies utilizing human coronary artery SMCs were conducted to examine the impact of YAP1 on contractility signaling components using western blotting. Results: Consistent with GWAS and RNAseq data, we found that YAP1 is upregulated in vascular tissues of spontaneously hypertensive rats (SHRs). Using aortic rings from WT mice, we discovered that Verteporfin significantly reduced vasoconstrictive responses to Phenylephrine or Serotonin but did not alter endothelium-dependent vasorelaxant responses to Acetylcholine, suggesting a specific role of YAP1 in VSMCs. Consistently, YAP1 iKO exhibited attenuated responses to vasoconstrictors in isolated conduit and resistance vessels. Importantly, radiotelemetry studies demonstrated for the first time that YAP1 iKO mice exhibit a hypotensive phenotype. Mechanistically, YAP1 gain- and loss-of-function studies in human VSMCs showed that YAP1 activates multiple signaling pathways that play a key role in VSMC contractility including RhoA/ROCK1/actin polymerization and PKC/ERK signaling pathways. Summary/Conclusion: This is the first study to demonstrate that inhibition of SM-specific-Yap1 expression regulates BP and vascular tone, likely via the regulation of contractile machinery components. Together, our data suggest that YAP1 is a promising novel therapeutic target for ameliorating hypertension. This work is supported by a grant from National Heart, Lung, and Blood Institute (R00HL153896). 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.

Elevated blood homocysteine increases the risk of incident Motoric Cognitive Risk syndrome: A two cohort study.

Motoric Cognitive Risk (MCR) syndrome, a pre-dementia syndrome characterized by cognitive complaints and slow gait, may have an underlying vascular etiology. Elevated blood levels of homocysteine, a known vascular risk factor, have been linked to physical and cognitive decline in older adults, though the relationship with MCR is unknown. We aimed to identify the association between homocysteine and MCR risk. We examined the association between baseline homocysteine levels and incident MCR using Cox proportional hazard models in 1,826 community-dwelling older adults (55% female) from two cohorts (Einstein Aging Study [EAS] and Quebec Longitudinal Study on Nutrition and Successful Aging [NuAge]). We calculated hazard ratios (HR) with 95% confidence intervals (CI), for each cohort as well as stratified by sex and vascular disease/risk factors. Median follow-up time was 2.2 years in EAS and 3.0 years in NuAge. Individuals with elevated baseline homocysteine levels (> 14 µmol/L) had a significantly higher risk of incident MCR compared to those with normal levels in NuAge (HR 1.41, 95% CI = 1.01-1.97, p = .04), after adjusting for covariates. Our exploratory stratified analyses found that these associations were significant only in men with vascular disease/risk factors. Higher blood homocysteine levels are associated with increased risk of developing MCR in older adults, particularly in men with vascular disease or vascular risk factors.

Profiles of Lifestyle Health Behaviors and Postmortem Dementia-Related Neuropathology.

High engagement in lifestyle health behaviors appears to be protective against cognitive decline in aging. We investigated the association between patterns of modifiable lifestyle health behaviors and common brain neuropathologies of dementia as a possible mechanism. We examined 555 decedents from the Rush Memory and Aging Project, free of dementia at their initial concurrent report of lifestyle health behaviors of interest (physical, social, and cognitive activities, and healthy diet), and who underwent a postmortem neuropathology evaluation. First, we used latent profile analysis to group participants based on baseline behavior patterns. Second, we assessed the associations of profile membership with each neurodegenerative (global Alzheimer's disease [AD] pathology, amyloid-beta load, density of neurofibrillary tangles, and presence of cortical Lewy bodies and TAR DNA-binding protein 43 cytoplasmic inclusions) and neurovascular pathologies (presence of chronic gross or microscopic infarcts, arteriolosclerosis, atherosclerosis, and cerebral amyloid angiopathy), using separate linear or logistic regression models, adjusted for age at death, sex (core model), vascular disease risk factors, and vascular conditions (fully adjusted model). Participants had either consistently lower (N = 224) or consistently higher (N = 331) engagement across 4 lifestyle health behaviors. We generally found no differences in neuropathologies between higher and lower engagement groups in core or fully adjusted models; for example, higher engagement in lifestyle health behaviors was not associated with global AD pathology after core or full adjustment (both p > .8). In conclusion, we found no evidence of associations between patterns of lifestyle health behaviors and neuropathology. Other mechanisms may underlie protective effects of health behaviors against dementia.

Effects of Vascular Disease Risk Factors on Brain ATP in People with Multiple Sclerosis—A 3-year Longitudinal Study (P11-6.010)

Effects of Vascular Disease Risk Factors on Brain ATP in People with Multiple Sclerosis—A 3-year Longitudinal Study (P11-6.010)

395 A History of Smoking Is Not an Independent Risk Factor for Perioperative Outcomes in Nontraumatic Subarachnoid Hemorrhage

INTRODUCTION: Nontraumatic Subarachnoid Hemorrhage (NSAH) is a rupture leading to blood accumulating in the subarachnoid region. Smoking contributes to vascular pathogenesis which can ultimately end in an aneurysm. Smoking and history of smoking often is a risk factor for complications perioperatively for vascular procedures, however patients receiving treatment for NSAH may have different perioperative outcome profiles. METHODS: Patients with NSAH who underwent neurosurgery were identified using ICD codes (ICD10, I60; ICD9, 430) in the ACS-NSQIP database from 2005-2021. Subjects were stratified into two study groups based on documented prior history of smoking: smokers or non-smokers. Significant preoperative differences were present between groups so a multivariable logistic regression was performed between patients with and without a prior history of smoking. The 30-day perioperative outcomes of patients with a prior history of smoking were compared to that of control. Perioperative outcomes included death, major adverse cardiovascular events (MACE), cardiac complications, stroke, wound complications, renal complications, sepsis, clot formation, pulmonary complications, return to the operating room, operation time greater than four hours, length of stay longer than 7 days, discharge not to home, and bleeding. RESULTS: There were 626 patients with a prior smoking history and 1336 patients with no prior smoking history. We found no significant difference between these two groups across all adverse outcomes analyzed. CONCLUSIONS: This study shows that although history of smoking is commonly a risk factor for vascular diseases and perioperative complications, it is not a risk factor for the perioperative variables analyzed when treating NSAH. Additional research should be done to determine if different procedures to treat NSAH may have different outcomes among smokers.

Stroke frequency, associated factors, and clinical features in primary systemic vasculitis: a multicentric observational study.

The cerebral vessels may be affected in primary systemic vasculitis (PSV), but little is known about cerebrovascular events (CVEs) in this population. This study aimed to determine the frequency of CVEs at the time of diagnosis of PSV, to identify factors associated with CVEs in PSV, and to explore features and outcomes of stroke in patients with PSV. Data from adults newly diagnosed with PSV within the Diagnostic and Classification Criteria in VASculitis (DCVAS) study were analysed. Demographics, risk factors for vascular disease, and clinical features were compared between patients with PSV with and without CVE. Stroke subtypes and cumulative incidence of recurrent CVE during a prospective 6-month follow-up were also assessed. The analysis included 4828 PSV patients, and a CVE was reported in 169 (3.50%, 95% CI 3.00-4.06): 102 (2.13% 95% CI 1.73-2.56) with stroke and 81 (1.68% 95% CI 1.33-2.08) with transient ischemic attack (TIA). The frequency of CVE was highest in Behçet's disease (9.5%, 95% CI 5.79-14.37), polyarteritis nodosa (6.2%, 95% CI 3.25-10.61), and Takayasu's arteritis (6.0%, 95% CI 4.30-8.19), and lowest in microscopic polyangiitis (2.2%, 95% CI 1.09-3.86), granulomatosis with polyangiitis (2.0%, 95% CI 1.20-3.01), cryoglobulinaemic vasculitis (1.9%, 95% CI 0.05-9.89), and IgA-vasculitis (Henoch-Schönlein) (0.4%, 95% CI 0.01-2.05). PSV patients had a 11.9% cumulative incidence of recurrent CVE during a 6-month follow-up period. CVEs affect a significant proportion of patients at time of PSV diagnosis, and the frequency varies widely among different vasculitis, being higher in Behçet's. Overall, CVE in PSV is not explained by traditional vascular risk factors and has a high risk of CVE recurrence.

The impact of sex on platelet responses to aspirin in patients with peripheral artery disease.

Women with peripheral artery disease (PAD) have poorer limb salvage outcomes in spite of having lower risk factors for vascular disease than their male counterparts. Mono antiplatelet therapy with aspirin is the cornerstone of medical treatment for PAD to reduce the risk of arterial thrombosis, but platelets in women may have a variable response to this standard of care compared to men. Viscoelastic assays, such as thromboelastography with platelet mapping (TEG-PM), have been utilized to identify prothrombotic states and may provide insight into a patient's real-time coagulation profile and their response to specific antiplatelet medications. The aim of this prospective, observational study was to delineate the sex differences in platelet function using TEG-PM in patients with PAD on aspirin post-revascularization for PAD. All patients with PAD undergoing revascularization on aspirin monotherapy were prospectively enrolled between December 2020 and September 2023. The cohort was divided by sex, demographics, medications, procedure type, and outcomes were documented. Serial perioperative TEG-PM assays (1, 3, and 6 months) were performed up to 6 months postoperatively and platelet function was evaluated in both groups. Statistical analysis between women and men was performed to identify sex-specific differences in platelet function. Over the study period, a total of 303 patients were enrolled. Of this cohort, 149 patients met the study criteria and 266 samples were analyzed; 52 (34.89%) were women and 97 (65.11%) were men. In the platelet mapping assay, women showed significantly greater MAActF and MAAA, than men (16.66 vs. 14.94, p < .03 and 37.26 vs. 32.38, p < .01, respectively) indicating stronger thrombotic propensity. Additionally, platelet inhibition was significantly lower in women compared to men (52.95% vs. 61.65%, p < .05). In clinical outcomes reported as thrombotic events, women showed significantly higher occlusion in the area of intervention than men (4 vs. 1, p < .05). There is a growing awareness of the variations in the natural course, underlying mechanisms, and resulting outcomes of cardiovascular conditions, including PAD, in relation to sex. In this study, women did not achieve the same levels of platelet inhibition and displayed a procoagulant tendency in comparison to men when administered aspirin. Overall, aspirin monotherapy may be potentially sufficient for men, but women may require increased doses and/or additional antiplatelet medications to achieve an equivalent therapeutic effect.

Hypertension and other vascular risk factors in patients with functional seizures

ObjectiveRecent literature has suggested that functional seizures are associated with an elevated risk for vascular disease and mortality. We investigated the prevalence of risk factors for vascular disease in patients who were admitted to the epilepsy monitoring unit. MethodsPatients who were admitted to the epilepsy monitoring unit and received a definitive diagnosis of either functional seizures or epilepsy were identified. Data collected included demographic, clinical characteristics, medication list, comorbidities, and scheduled blood pressure measurements that occurred every 12 h during the admission. The mean blood pressures were calculated and if they were above the American College of Cardiology and the American Heart Association guideline cutoff of 130/80 mm Hg or the patient had a documented history of hypertension the patient was counted as having the condition. A multiple logistic regression model was developed to evaluate the independent association of the patient’s diagnosis (i.e., epilepsy or functional seizures) and vascular risk factors that controlled for the number of blood pressure measurements, age, sex, and if the patient was taking antihypertensive medications. Results270 patients were included in this study of which 147 patients had epilepsy and 123 had functional seizures. Among those with functional seizures, 57.72 % had either a history of hypertension or a mean blood pressure above 130/80 compared to 38.78 % of those with epilepsy (p = 0.0022). In addition, 30.89 % of functional seizures patients had hyperlipidemia and 63.41 % were obese. The logistic regression model indicated that functional seizures were independently associated with high blood pressure (OR: 2.47, 95 % CI 1.10–5.69), hyperlipidemia (OR: 3.38, 95 % CI 1.35–8.86), and obesity (OR: 4.25, 95 % CI 2.22–8.36) compared to those with epilepsy. There was no significant difference in the prevalence of diabetes (OR: 0.81, 95 % CI 0.24–2.77) or current tobacco use (OR: 1.04, 95 % CI 0.48–2.25) between the groups. SignificancePatients with functional seizures had an elevated prevalence of several vascular risk factors. These findings may partially account for complications associated with functional seizures and have implications related to their pathophysiology.

Comparative vascular effects of levetiracetam and valproate with hyperhomocysteinemia in rat models

Abstract Objectives Hyperhomocysteinemia (HHcy) a significant risk factor for vascular disease, often emerges in epilepsy with the use of antiepileptic drugs. In this relationship, our study investigates the combined effects of HHcy and antiepileptics on vascular function using a rat model. Methods Fourty two rats were included and divided into six groups as, 1-Control, 2-L-Met, 3-LEV injected, 4-LEV-injected + L-Met, 5-VAL-injected, 6-VAL injected + L-Met. L-Methionine (L-Met) was added to drinking water of rats for 1 month to develop HHcy. Simultaneously, intraperitoneal (ip) injections of sodium valproate (VAL) and levetiracetam (LEV) were administered. Effects were comparatively investigated, and noradrenaline (NA), followed by acetylcholine (ACh) and glyceryl trinitrate (GTN) were applied in organ bath system. Agonist doses were expressed as ten base logarithm (M) through 10−9, 10−8, 10−7, 10−6, 10−5, 10−4 mol/L in dose-response graph. Results NA contractions between LEV and LEV + L-Met groups showed statistical significance (LEV Emax=288.50 ± 46.54, LEV + L-Met Emax=480.40 ± 78.83) (p&lt;0.05) however, no significance was observed among the other groups. ACh relaxations between Control-L-Met (Control Inhmax=12.65 ± 2.09, L-Met Inhmax=50.05 ± 7.43) (p&lt;0.05), and Control-Val + L-Met (Control Emax=328.20 ± 52.83, VAL + L-Met Emax=452.60 ± 71.53) (p&lt;0.01), groups showed statistical significance. Between other groups, no significance was observed. In GTN relaxations, no statistical significance was observed. Conclusions This study highlights the adverse impact of HHcy on aortic relaxation. Further impairment was observed with VAL compared to other treatment and control groups. These findings underscore the importance of considering vascular side effects when selecting antiepileptic drugs. Ultimately, our study contributes valuable insights that may aid the choice of appropriate treatment strategies to mitigate potential vascular complications of HHcy.

Current Smoking Status Is Not a Risk Factor for Perioperative Outcomes in Patients with Aneurysmal Subarachnoid Hemorrhage Who Underwent Craniotomy Repair

BackgroundAneurysmal subarachnoid hemorrhage is a rupture leading to blood accumulating in the subarachnoid region. Smoking status often is a risk factor for postoperative complications for vascular procedures. This study aims to retrospectively examine the effect of being a current tobacco smoker on postoperative outcomes in nontraumatic subarachnoid hemorrhage patients. MethodsPatients with aneurysmal subarachnoid hemorrhage who underwent craniotomy were identified in the ACS-NSQIP database. The 30-day perioperative outcomes of current smokers were compared to that of control, which was patients who have not smoked tobacco in the past year. Postoperative outcomes included death, cardiac complications, stroke, operation time greater than four hours, bleeding, and other events. Additionally, this studied examined the same surgical outcomes in patients over age 65. ResultsWe found no significant difference between these two groups across all adverse outcomes analyzed. In age>65, we again found no significant different between these two groups across all adverse outcomes analyzed. ConclusionsThis study shows that although current tobacco smoker status is commonly a risk factor for vascular diseases and postoperative complications, it is not a risk factor for the postoperative variables we analyzed during craniotomy for aneurysmal subarachnoid hemorrhage. Additional research should be conducted to determine if different procedures to treat aneurysmal subarachnoid hemorrhage may have different outcomes among smokers.

Associations between homocysteine, tau, and neurodegenerative markers in apolipoprotein ε4 non‐carriers with clinical Alzheimer’s disease

AbstractBackgroundHomocysteine (Hcy) is an amino acid generated as a byproduct of methionine metabolism. It is a risk factor for vascular and neurodegenerative diseases. This study investigated relationships between plasma Hcy concentrations and neurodegenerative biomarkers in people clinically diagnosed with Alzheimer’s disease (AD) or mild cognitive impairment (MCI) due to AD.MethodParticipants were identified from the Ontario Neurodegenerative Disease Research Initiative. Brain parenchymal fraction (BPF) was quantified using T1‐ and T2‐weighted structural magnetic resonance imaging with an in‐house Semi‐Automated Brain Region Extraction and Lesion Explorer package. Plasma amyloid beta (Aβ) 42, Aβ40, phosphorylated tau 181 (p‐tau181), and neurofilament light chain (NfL) were measured with Single molecule array (Simoa) assays. Linear regression analyses were used to test associations between Hcy and neuroimaging or plasma biomarkers, controlling for age, sex, hypertension, hyperlipidemia, diabetes, cholesterol, and vitamin B12. Analyses were stratified by apolipoprotein E (APOE) ε4 carrier status (non‐carriers: n = 64, mean age = 70.9 years, 41% female; carriers: n = 62, mean age = 71.2 years, 50% female).ResultIn APOE ε4 non‐carriers, Hcy was associated negatively with BPF (β = ‐0.233, p = 0.047, 95% CI [‐0.460, ‐0.003]), notably in temporal lobe regions in exploratory regional analyses. Hcy was also associated positively with plasma concentrations of NfL (β = 0.403, p = 0.007, 95% CI [0.117, 0.688]) and p‐tau181 (β = 0.357, p = 0.023, 95% CI [0.051, 0.663]) in APOE ε4 non‐carriers. Also, in APOE ε4 non‐carriers, Hcy was associated positively with Aβ40 (β = 0.367, p = 0.015, 95% CI [0.074, 0.660]) and Aβ42 (β = 0.305, p = 0.041, 95% CI [0.012, 0.598]), but not with the Aβ42/40 ratio (β = 0.155, p = 0.339, 95% CI [‐0.166, 0.476]). None of these associations were seen in APOE ε4 carriers.ConclusionIn non‐carriers of the APOE ε4 allele clinically diagnosed with AD or MCI, homocysteine was associated with Amyloid, tau and neurodegeneration. The specificity of these relationships to ε4 non‐carriers identifies a unique risk factor profile for AD that is independent of APOE ε4 status.

Central positional nystagmus due to acute medial medullary infarction

A 70-year-old male with risk factors for vascular disease presented with dizziness and instability. The patient showed horizontal geotropic nystagmus when turning his head while lying down, with larger slow phase velocity observed when turning to the left. There were no other neurological deficits. Video head impulse tests and vestibular evoked myogenic potentials were normal. The initial magnetic resonance imaging (MRI) findings were negative; however, the patient experienced subsequent right-side weakness, right tilting, and recurrent episodes of vertigo. A follow-up MRI revealed an acute left medial medullary infarction, which seems to have caused the paroxysmal geotropic central positional nystagmus in this patient.

Is it possible to get a two-for-one? Can we slow cognitive decline by treating vascular disease risk factors?

Is it possible to get a two-for-one? Can we slow cognitive decline by treating vascular disease risk factors?

Quantitative and Qualitative Characteristics of Atherosclerotic Plaques on Carotid Arteries in Patients with Antiphospholipid Syndrome: The Role of MDCT Angiography.

Antiphospholipid syndrome (APS) is an autoimmune disease characterised by arterious and venous thrombosis, miscarriage, and the presence of antiphospholipid antibodies (aPL) in the blood. As we know, APS is also characterised by accelerated atherosclerotic degeneration with an increased risk of thrombosis in all blood vessels, including the carotid arteries. Carotid artery stenosis can manifest in many different ways. The aim of this study is to present the results of our multidetector computerised tomography angiography (MDCTA) analysis of the carotid arteries in patients with primary and secondary APS compared with a control group. This study examined 50 patients with primary antiphospholipid syndrome (PAPS) and 50 patients with secondary antiphospholipid syndrome (SAPS). The results were compared with a control group also comprising 50 patients. The groups were analysed with respect to age, sex and the presence of well-established risk factors for vascular disease. The study was conducted using MDCTA, where we analysed the quantitative and qualitative (morphologic) characteristics of carotid artery lesions. Patients from the control group had significantly elevated levels of cholesterol and triglycerides in comparison with patients with PAPS and SAPS (p < 0.001 and p < 0.05). The results show that carotid artery lesions were significantly more common in patients with APS (PAPS, n = 40, CI95: 0.50-0.75, p = 0.0322 and SAFS, n = 54, CI95: 0.59-0.80, p = 0.0004) than within the control group (n = 23). There was a statistically significant difference between patients with APS and the control group with respect to lesions in the distal segments (n = 27, CI95: 0.67-0.95, p = 0.0001), bulbi and proximal segments (n = 21, CI95: 0.84-1.00, p = 0.000005). The number of patients with one lesion (L) (n = 27) was significantly greater than the number of those with three (n = 10, CI95: 0.56-0.86, p = 0.0051) or four (n = 3, CI95: 0.73-0.98, p = 0.00001) lesions. There were also more patients with two lesions (n = 24) than those with four (n = 3) (CI95: 0.71-0.97, p = 0.00005). Carotid artery stenosis was shown as a percentage of the carotid artery lumen diameter (%DS). Stenosis of up to 30%, was more common in patients in the PAPS group (n = 12) than in the control group (n = 3) (CI95: 0.52-0.96, p = 0.0201), while the SAPS group (n = 17) had an even larger disparity (CI95: 0.62-0.97, p = 0.0017). We observed a highly significant difference in the frequency of stenoses between 30% and 50% DS between the PAPS group (n = 24) and the control group (n = 7) (CI95: 0.59-0.90, p = 0.0023), as well as the SAPS group (n = 30) (CI95: 0.65-0.92, p = 0.0002). A qualitative analysis of plaque morphology revealed that patients with PAPS had significantly more soft tissue lesions (n = 23) compared with calcified lesions (n = 2) (CI95: 0.74-0.99, p = 0.00003), as well as more mixed plaques (n = 9) and calcified plaques (n = 2) (CI95: 0.48-0.98, p = 0.0348). Patients within the SAPS group had significantly more soft tissue (n = 35) than calcified lesions (n = 3) (CI95: 0.79-0.98, p = 0.00000021), as well as more mixed lesions (n = 21) compared with calcified (n = 3) (CI95: 0.68-0.97, p = 0.0002). Our study shows that subclinical manifestations of carotid artery lesions were more common in patients with APS. We came to the conclusion that MDCTA is an accurate diagnostic method because it is a safe method that provides us with a great quantity of accurate information about the characteristics of atheromatous plaques, which aids us in the further planning of treatment for patients with APS.

Epigenetic Reader Bromodomain-Containing Protein 4 in Aging-Related Vascular Pathologies and Diseases: Molecular Basis, Functional Relevance, and Clinical Potential.

Aging is a key independent risk factor of various vascular diseases, for which the regulatory mechanisms remain largely unknown. Bromodomain-containing protein 4 (BRD4) is a member of the Bromodomain and Extra-Terminal domain (BET) family and is an epigenetic reader playing diverse roles in regulating transcriptional elongation, chromatin remodeling, DNA damage response, and alternative splicing in various cells and tissues. While BRD4 was initially recognized for its involvement in cancer progression, recent studies have revealed that the aberrant expression and impaired function of BRD4 were highly associated with aging-related vascular pathology, affecting multiple key biological processes in the vascular cells and tissues, providing new insights into the understanding of vascular pathophysiology and pathogenesis of vascular diseases. This review summarizes the recent advances in BRD4 biological function, and the progression of the studies related to BRD4 in aging-associated vascular pathologies and diseases, including atherosclerosis, aortic aneurism vascular neointima formation, pulmonary hypertension, and essential hypertension, providing updated information to advance our understanding of the epigenetic mechanisms in vascular diseases during aging and paving the way for future research and therapeutic approaches.

Assessment of cheese sign and its association with vascular risk factors: Data from PUMCH dementia cohort.

In the clinic, practitioners encounter many patients with an abnormal pattern of dense punctate magnetic resonance imaging (MRI) signal in the basal ganglia, a phenomenon known as "cheese sign". This sign is reported as common in cerebrovascular diseases, dementia, and old age. Recently, cheese sign has been speculated to consist of dense perivascular space (PVS). This study aimed to assess the lesion types of cheese sign and analyze the correlation between this sign and vascular disease risk factors. A total of 812 patients from Peking Union Medical College Hospital (PUMCH) dementia cohort were enrolled. We analyzed the relationship between cheese sign and vascular risk. For assessing cheese sign and defining its degree, the abnormal punctate signals were classified into basal ganglia hyperintensity (BGH), PVS, lacunae/infarctions and microbleeds, and counted separately. Each type of lesion was rated on a four-level scale, and then the sum was calculated; this total was defined as the cheese sign score. Fazekas and Age-Related White Matter Changes (ARWMC) scores were used to evaluate the paraventricular, deep, and subcortical gray/white matter hyperintensities. A total of 118 patients (14.5%) in this dementia cohort were found to have cheese sign. Age (odds ratio [OR]: 1.090, 95% confidence interval [CI]: 1.064-1.120, P <0.001), hypertension (OR: 1.828, 95% CI: 1.123-2.983, P = 0.014), and stroke (OR: 1.901, 95% CI: 1.092-3.259, P = 0.025) were risk factors for cheese sign. There was no significant relationship between diabetes, hyperlipidemia, and cheese sign. The main components of cheese sign were BGH, PVS, and lacunae/infarction. The proportion of PVS increased with cheese sign severity. The risk factors for cheese sign were hypertension, age, and stroke. Cheese sign consists of BGH, PVS, and lacunae/infarction.

Unilateral cerebral arterial tortuosity: Associated with aneurysm occurrence, but potentially inversely associated with aneurysm rupture

PurposeTo investigate the association of tortuosity of the main cerebral arteries with intracranial aneurysm (IA) occurrence and rupture. To investigate the relationship between arterial tortuosity and aneurysm morphology as well as conventional risk factors of vascular diseases. MethodsThree subject groups were analyzed in this study: Patients with ruptured IAs, patients with unruptured IAs, and healthy subjects. The groups were matched by sex and age using tendency score matching. Their intracranial magnetic resonance angiography (MRA) images were collected retrospectively. The intracranial arterial structures were segmented from the MRA images. Arterial tortuosity was measured and statistically compared between the different subject groups and different vessels. Correlation analysis was conducted between arterial tortuosity and clinical risk factors as well as aneurysm morphology. Results120 patients were included in the study (average age: 67.5 years; 60% female), 40 for each group after matching. The tortuosity of the aneurysm-bearing artery was significantly greater than that of the contralateral artery in both the ruptured and unruptured IA groups (p < 0.001). There was no significant association between clinical risk factors (history of hypertension, hyperlipidemia, diabetes, smoking, and alcohol use) and arterial tortuosity. There were significant negative correlations between aneurysm-bearing artery tortuosity and aneurysm morphological features such as maximal diameter (p = 0.0011), neck diameter (p < 0.0001), maximum height (p = 0.0024), and size ratio (p = 0.0269). ConclusionThe occurrence of cerebral aneurysms correlates to increased unilateral arterial tortuosity, but the risk of aneurysm enlargement/rupturing decreases with greater arterial tortuosity. Abnormal tortuosity may be congenital as tortuosity has no clear connection with acquired common risk factors of vascular diseases.

No relationship between right-to-left shunt with the severity of white matter hyperintensities

IntroductionStudies have shown that right-to-left shunt (RLS) is closely related to the occurrence of white matter hyperintensities (WMHs). Therefore, the detection of RLS is of great significance for the diagnosis and treatment of cerebral small vessel disease, especially for the prevention and treatment of WMHs. In this study, the c-TCD foaming experiment was selected to screen RLS, and evaluate the correlation between RLS and the severity of WMHs. MethodsWe enrolled 334 migraineurs from a multicentre study from July 1 2019 and January 31 2020. Participants were all evaluated using contrast-enhanced transcranial Doppler, magnetic resonance imaging (MRI), and completed a questionnaire covering demographics, the main risk factors of vascular disease, and migraine status. RLS was classified into four grades (Grade 0 = Negative; Grade I = 1 ≤microbubbles (MBs)≤ 10; Grade II = MBs > 10 and no curtain; Grade III = curtain). Silent brain ischemic infarctions (SBI) and white matter hyperintensities (WMHs) were evaluated on MRI. ResultsIn the incidence of WMHs, we found a significant difference between patients with RLS and no RLS (p < 0.05). There is no relationship between different grades of RLS and the severity of WMHs (p > 0.05). ConclusionOverall, the positive rate of RLS is related to the incidence of WMHs. The different grades of RLS have no-relationship to do with the severity of WMHs.

Cigarette Smoke-Induced Respiratory Response: Insights into Cellular Processes and Biomarkers.

Cigarette smoke (CS) poses a significant risk factor for respiratory, vascular, and organ diseases owing to its high content of harmful chemicals and reactive oxygen species (ROS). These substances are known to induce oxidative stress, inflammation, apoptosis, and senescence due to their exposure to environmental pollutants and the presence of oxidative enzymes. The lung is particularly susceptible to oxidative stress. Persistent oxidative stress caused by chronic exposure to CS can lead to respiratory diseases such as chronic obstructive pulmonary disease (COPD), pulmonary fibrosis (PF), and lung cancer. Avoiding exposure to environmental pollutants, like cigarette smoke and air pollution, can help mitigate oxidative stress. A comprehensive understanding of oxidative stress and its impact on the lungs requires future research. This includes identifying strategies for preventing and treating lung diseases as well as investigating the underlying mechanisms behind oxidative stress. Thus, this review aims to investigate the cellular processes induced by CS, specifically inflammation, apoptosis, senescence, and their associated biomarkers. Furthermore, this review will delve into the alveolar response provoked by CS, emphasizing the roles of potential therapeutic target markers and strategies in inflammation and oxidative stress.