Journal of Vascular Research最新文献

{"title":"Microvessel Density: Integrating Sex-Based Differences and Elevated Cardiovascular Risks in Metabolic Syndrome.","authors":"Angelina Wong,&nbsp;Shu Qing Chen,&nbsp;Brayden D Halvorson,&nbsp;Jefferson C Frisbee","doi":"10.1159/000518787","DOIUrl":"https://doi.org/10.1159/000518787","url":null,"abstract":"<p><p>Metabolic syndrome (MetS) is a complex pathological state consisting of metabolic risk factors such as hypertension, insulin resistance, and obesity. The interconnectivity of cellular pathways within various biological systems suggests that each individual component of MetS may share common pathological sources. Additionally, MetS is closely associated with vasculopathy, including a reduction in microvessel density (MVD) (rarefaction) and elevated risk for various cardiovascular diseases. Microvascular impairments may contribute to perfusion-demand mismatch, where local metabolic needs are insufficiently met due to the lack of nutrient and oxygen supply, thus creating pathological positive-feedback loops and furthering the progression of disease. Sexual dimorphism is evident in these underlying cellular mechanisms, which places males and females at different levels of risk for cardiovascular disease and acute ischemic events. Estrogen exhibits protective effects on the endothelium of pre-menopausal women, while androgens may be antagonistic to cardiovascular health. This review examines MetS and its influences on MVD, as well as sex differences relating to the components of MetS and cardiovascular risk profiles. Finally, translational relevance and interventions are discussed in the context of these sex-based differences.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39427161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-Cell RNA Sequencing Reveals Novel Genes Regulated by Hypoxia in the Lung Vasculature.","authors":"Shelby Thomas,&nbsp;Sathiyanarayanan Manivannan,&nbsp;Vidu Garg,&nbsp;Brenda Lilly","doi":"10.1159/000522340","DOIUrl":"https://doi.org/10.1159/000522340","url":null,"abstract":"<p><p>Pulmonary arterial hypertension (PAH) is a chronic progressive disease with significant morbidity and mortality. The disease is characterized by vascular remodeling that includes increased muscularization of distal blood vessels and vessel stiffening associated with changes in extracellular matrix deposition. In humans, chronic hypoxia causes PAH, and hypoxia-induced rodent models of PAH have been used for years to study the disease. With the development of single-cell RNA sequencing technology, it is now possible to examine hypoxia-dependent transcriptional changes in vivo at a cell-specific level. In this study, we used single-cell RNA sequencing to compare lungs from wild-type (Wt) mice exposed to hypoxia for 28 days to normoxia-treated control mice. We additionally examined mice deficient for Notch3, a smooth muscle-enriched gene linked to PAH. Data analysis revealed that hypoxia promoted cell number changes in immune and endothelial cell types in the lung, activated the innate immunity pathway, and resulted in specific changes in gene expression in vascular cells. Surprisingly, we found limited differences in lungs from mice deficient for Notch3 compared to Wt controls. These findings provide novel insight into the effects of chronic hypoxia exposure on gene expression and cell phenotypes in vivo and identify unique changes to cells of the vasculature.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9117417/pdf/nihms-1779393.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9484790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microstructural Characterization of Resistance Artery Remodelling in Diabetes Mellitus.","authors":"James S Bell,&nbsp;Aminat O Adio,&nbsp;Andrew Pitt,&nbsp;Lindsay Hayman,&nbsp;Clare E Thorn,&nbsp;Angela C Shore,&nbsp;Jacqueline L Whatmore,&nbsp;C Peter Winlove","doi":"10.1159/000517856","DOIUrl":"https://doi.org/10.1159/000517856","url":null,"abstract":"<p><strong>Introduction: </strong>Microvascular remodelling is a symptom of cardiovascular disease. Despite the mechanical environment being recognized as a major contributor to the remodelling process, it is currently only understood in a rudimentary way.</p><p><strong>Objective: </strong>A morphological and mechanical evaluation of the resistance vasculature in health and diabetes mellitus.</p><p><strong>Methods: </strong>The cells and extracellular matrix of human subcutaneous resistance arteries from abdominal fat biopsies were imaged using two-photon fluorescence and second harmonic generation at varying transmural pressure. The results informed a two-layer mechanical model.</p><p><strong>Results: </strong>Diabetic resistance arteries reduced in wall area as pressure was increased. This was attributed to the presence of thick, straight collagen fibre bundles that braced the outer wall. The abnormal mechanical environment caused the internal elastic lamina and endothelial and vascular smooth muscle cell arrangements to twist.</p><p><strong>Conclusions: </strong>Our results suggest diabetic microvascular remodelling is likely to be stress-driven, comprising at least 2 stages: (1) Laying down of adventitial bracing fibres that limit outward distension, and (2) Deposition of additional collagen in the media, likely due to the significantly altered mechanical environment. This work represents a step towards elucidating the local stress environment of cells, which is crucial to build accurate models of mechanotransduction in disease.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8820441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39433068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Microvascular-Lymphatic Interface and Tissue Homeostasis: Critical Questions That Challenge Current Understanding.","authors":"Arinola O Lampejo,&nbsp;Michiko Jo,&nbsp;Walter L Murfee,&nbsp;Jerome W Breslin","doi":"10.1159/000525787","DOIUrl":"10.1159/000525787","url":null,"abstract":"<p><p>Lymphatic and blood microvascular networks play critical roles in the clearance of excess fluid from local tissue spaces. Given the importance of these dynamics in inflammation, tumor metastasis, and lymphedema, understanding the coordinated function and remodeling between lymphatic and blood vessels in adult tissues is necessary. Knowledge gaps exist because the functions of these two systems are typically considered separately. The objective of this review was to highlight the coordinated functional relationships between blood and lymphatic vessels in adult microvascular networks. Structural, functional, temporal, and spatial relationships will be framed in the context of maintaining tissue homeostasis, vessel permeability, and system remodeling. The integration across systems will emphasize the influence of the local environment on cellular and molecular dynamics involved in fluid flow from blood capillaries to initial lymphatic vessels in microvascular networks.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9780194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10442722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What Went Wrong with VEGF-A in Peripheral Arterial Disease? A Systematic Review and Biological Insights on Future Therapeutics.","authors":"Stavroula L Kastora,&nbsp;Jonathan Eley,&nbsp;Martin Gannon,&nbsp;Ross Melvin,&nbsp;Euan Munro,&nbsp;Sotirios A Makris","doi":"10.1159/000527079","DOIUrl":"https://doi.org/10.1159/000527079","url":null,"abstract":"<p><strong>Background: </strong>Of the 200 million patients worldwide affected by peripheral arterial disease (PAD), 4% will inevitably require major limb amputation. Previous systematic reviews presented a conflicting body of evidence in terms of vascular endothelial growth factor (VEGF) family member effects upon PAD natural progression. Despite that, modulation of intrinsic angiogenesis mechanisms targeting the VEGF family members still confers an attractive therapeutic target. The aim of the present study was to evaluate current evidence of VEGF modulation in the context of PAD.</p><p><strong>Methods: </strong>This is a systematic literature review conducted according to the PRISMA guidelines and registered under PROSPERO database [CRD42021285988]. Independent literature search was performed up to April 1, 2022, on six databases. A total of 22 eligible studies were identified [N: 3, interventional patient studies; N: 19, animal studies]. Animal studies were appraised by the SYRCLE risk of bias tool, while human participant studies were assessed by the Newcastle Ottawa scale. Overall, quality of evidence was deemed fair for both animal and human studies. Main study outcomes were percentage change of injured vessel lumen stenosis and neointimal area formation upon VEGF modulation (inhibition or activation) in comparison with control group.</p><p><strong>Findings: </strong>Nineteen animal models and three human participant studies were included in the systematic review and assessed separately. Positive modulation of VEGF-A in animal models resulted in a median decrease of 65.58% [95% CI 45.2; 71.87] in lumen stenosis [14 studies]. Furthermore, positive modulation of VEGF-A was found to reduce neointimal area proliferation by a median decrease of 63.41% [95% CI 41.6; 79.59] [14 studies]. Median end of study duration was 28 days [range: 14-84 days]. Data were insufficient to assess these outcomes with respect to VEGF-B or VEGF-C modulation. The limited number of available human studies presented inadequate outcome assessment despite their overall fair NOS grading.</p><p><strong>Interpretation: </strong>VEGF-A-positive modulation decreases lumen stenosis and neointimal hyperplasia in PAD simulation animal models. Previously identified variability among outcomes was found to strongly stem from the variability of experimental designs. Clinical applicability and safety profile of VEGF-A in the context of PAD remain to be defined by a robust and uniformly designed body of further animal model-based experiments.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9808638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10487219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum.","authors":"","doi":"10.1159/000525392","DOIUrl":"https://doi.org/10.1159/000525392","url":null,"abstract":"","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10235181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Experimental Atherosclerosis Research on Large and Small Animal Models in Vascular Surgery.","authors":"Florian Simon,&nbsp;Axel Larena-Avellaneda,&nbsp;Sabine Wipper","doi":"10.1159/000524795","DOIUrl":"https://doi.org/10.1159/000524795","url":null,"abstract":"<p><p>Animal models have significantly advanced our understanding of the mechanisms of atherosclerosis formation and the evaluation of therapeutic options. The current focus of research is on preventive strategies and includes pharmacologic and biologic interventions directed primarily against smooth-muscle cell proliferation, endovascular devices for recanalization and/or drug delivery, and an integrated approach using both devices and pharmacobiologic agents. The experience over many decades with animal models in vascular research has established that a single, ideal, naturally available model for atherosclerosis does not exist. The spectrum ranges from large animals such as pigs to small animal experiments with genetically modified rodents such as the ApoE-/- mouse with correspondingly differently pronounced changes in their lipid and lipoprotein levels. The development of transgenic variants of currently available models, e.g., an ApoE-deficient rabbit line, has widened our options. Nevertheless, an appreciation of the individual features of natural or stimulated disease in each species is of importance for the proper design and execution of relevant experiments.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9533439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40404060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vascular Smooth Muscle Cells Mechanosensitive Regulators and Vascular Remodeling.","authors":"Shangmin Liu,&nbsp;Zhanyi Lin","doi":"10.1159/000519845","DOIUrl":"https://doi.org/10.1159/000519845","url":null,"abstract":"<p><p>Blood vessels are subjected to mechanical loads of pressure and flow, inducing smooth muscle circumferential and endothelial shear stresses. The perception and response of vascular tissue and living cells to these stresses and the microenvironment they are exposed to are critical to their function and survival. These mechanical stimuli not only cause morphological changes in cells and vessel walls but also can interfere with biochemical homeostasis, leading to vascular remodeling and dysfunction. However, the mechanisms underlying how these stimuli affect tissue and cellular function, including mechanical stimulation-induced biochemical signaling and mechanical transduction that relies on cytoskeletal integrity, are unclear. This review focuses on signaling pathways that regulate multiple biochemical processes in vascular mesangial smooth muscle cells in response to circumferential stress and are involved in mechanosensitive regulatory molecules in response to mechanotransduction, including ion channels, membrane receptors, integrins, cytoskeletal proteins, nuclear structures, and cascades. Mechanoactivation of these signaling pathways is closely associated with vascular remodeling in physiological or pathophysiological states.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39747088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral L-Arginine (5 g/day) for 14 Days Improves Microcirculatory Function in Healthy Young Women and Healthy and Type 2 Diabetes Mellitus Elderly Women.","authors":"Gerusa Costa,&nbsp;Milenna Shushanof,&nbsp;Eliete Bouskela,&nbsp;Daniel Bottino","doi":"10.1159/000519428","DOIUrl":"https://doi.org/10.1159/000519428","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study was to investigate the effect of oral supplementation with L-arginine on serum biochemical profile, blood pressure, microcirculation, and vasoreactivity/endothelial function in young controls, and elderly women with and without type 2 diabetes mellitus (T2DM).</p><p><strong>Methods: </strong>Healthy young (n = 25), healthy elderly (n = 25), and elderly women with type 2 diabetes mellitus (T2DME, n = 23, glycated Hb ≥6.4% and mean of 7.7 years for duration of the disease), aged 18-30 and older than 65 years, respectively, were included in the study. All patients underwent biochemical analysis (fasting glycemia and lipidogram), arterial blood pressure, nailfold videocapillaroscopy (capillary diameters, functional capillary density [FCD], peak red blood cell velocity [RBCVmax] after 1 min ischemia, time to reach peak RBCV [TRBCVmax]), and venous occlusion plethysmography (vasoreactivity), before and after 14 days of oral supplementation with L-arginine (5 g/day).</p><p><strong>Results: </strong>L-Arginine did not change fasting glycemia and lipidogram, but it decreased systolic, diastolic, and mean arterial pressure in elderly women, increased RBCVmax in all groups, and did not decrease TRBCVmax in T2DME. Capillary diameters and FCD remained unchanged in all groups. L-Arginine improved vasoreactivity during reactive hyperemia and after sublingual nitroglycerin (0.4 mg) in all groups.</p><p><strong>Conclusion: </strong>L-Arginine supplementation (5g/day during 14 days) was able to improve vascular/microvascular health in the elderly women with or without T2DM.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39882282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Blood Pressure Responses to Exercise and Vascular Insulin Sensitivity with Nocturnal Blood Pressure Dipping in Metabolic Syndrome.","authors":"Nathan R Stewart, Emily M Heiston, Stephanie L Miller, Anna C Ballantyne, Udeyvir S Cheema, Andrea M Spaeth, Peter Kokkinos, Steven K Malin","doi":"10.1159/000522063","DOIUrl":"10.1159/000522063","url":null,"abstract":"<p><strong>Introduction: </strong>Nocturnal systolic blood pressure (SBP) dipping is independently related to cardiovascular disease risk, but it is unclear if vascular insulin sensitivity associates with SBP dipping in patients with metabolic syndrome (MetS).</p><p><strong>Methods: </strong>Eighteen adults with MetS (ATP III criteria 3.3 ± 0.6; 53.2 ± 6.5 years; body mass index 35.8 ± 4.5 kg/m2) were categorized as \"dippers\" (≥10% change in SBP; n = 4 F/3 M) or \"non-dippers\" (<10%; n = 9 F/2 M). Twenty-four-hour ambulatory blood pressure was recorded to assess SBP dipping. A euglycemic-hyperinsulinemic clamp (40 mU/m2/min, 90 mg/dL) with ultrasound (flow mediated dilation) was performed to test vascular insulin sensitivity. A graded, incremental exercise test was conducted to estimate sympathetic activity. Heart rate (HR) recovery after exercise was then used to determine parasympathetic activity. Metabolic panels and body composition (DXA) were also tested.</p><p><strong>Results: </strong>Dippers had greater drops in SBP (16.63 ± 5.2 vs. 1.83 ± 5.6%, p < 0.01) and experienced an attenuated rise in both SBPslope (4.7 ± 2.3 vs. 7.2 ± 2.5 mm Hg/min, p = 0.05) and HRslope to the incremental exercise test compared to non-dippers (6.5 ± 0.9 vs. 8.2 ± 1.7 bpm/min, p = 0.03). SBP dipping correlated with higher insulin-stimulated flow-mediated dilation (r = 0.52, p = 0.03), although the relationship was no longer significant after covarying for HRslope (r = 0.42, p = 0.09).</p><p><strong>Conclusion: </strong>Attenuated rises in blood pressure and HR to exercise appear to play a larger role than vascular insulin sensitivity in SBP dipping in adults with MetS.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10848781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43041951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}