Journal of Vascular Research最新文献

{"title":"Smooth Muscle Cell Notch2 Is Not Required for Atherosclerotic Plaque Formation in ApoE Null Mice.","authors":"Jessica Davis-Knowlton,&nbsp;Jacqueline E Turner,&nbsp;Anne Harrington,&nbsp;Lucy Liaw","doi":"10.1159/000525258","DOIUrl":"https://doi.org/10.1159/000525258","url":null,"abstract":"<p><strong>Introduction: </strong>We previously identified Notch2 in smooth muscle cells (SMC) in human atherosclerosis and found that signaling via Notch2 suppressed human SMC proliferation. Thus, we tested whether loss of Notch2 in SMC would alter atherosclerotic plaque progression using a mouse model.</p><p><strong>Methods: </strong>Atherogenesis was examined at the brachiocephalic artery and aortic root in a vascular SMC null (inducible smooth muscle myosin heavy chain Cre) Notch2 strain on the ApoE-/- background. We measured plaque morphology and size, as well as lipid, inflammation, and smooth muscle actin content after Western diet.</p><p><strong>Results: </strong>We generated an inducible SMC Notch2 null on the ApoE-/- background. We observed ∼90% recombination efficiency with no detectable Notch2 in the SMC. Loss of SMC Notch2 did not significantly change plaque size, lipid content, necrotic core, or medial area. However, loss of SMC Notch2 reduced the contractile SMC in brachiocephalic artery lesions and increased inflammatory content in aortic root lesions after 6 weeks of Western diet. These changes were not present with loss of SMC Notch2 after 14 weeks of Western diet.</p><p><strong>Conclusions: </strong>Our data show that loss of SMC Notch2 does not significantly reduce atherosclerotic lesion formation, although in early stages of plaque formation there are changes in SMC and inflammation.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":"59 5","pages":"261-274"},"PeriodicalIF":1.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9588530/pdf/nihms-1815853.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9762783","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":"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":"59 3","pages":"163-175"},"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":"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":"59 1","pages":"151-162"},"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}

{"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":"59 2","pages":"90-113"},"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":"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":"59 5","pages":"324"},"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":"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":"59 6","pages":"327-342"},"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":"59 6","pages":"381-393"},"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":"Quantification of Lipid Area within Thermogenic Mouse Perivascular Adipose Tissue Using Standardized Image Analysis in FIJI.","authors":"Benjamin W Tero, Bethany Fortier, Ashley N Soucy, Ginger Paquette, Lucy Liaw","doi":"10.1159/000517178","DOIUrl":"10.1159/000517178","url":null,"abstract":"<p><p>Quantification of adipocyte size and number is routinely performed for white adipose tissues using existing image analysis software. However, thermogenic adipose tissue has multilocular adipocytes, making it difficult to distinguish adipocyte cell borders and to analyze lipid proportion using existing methods. We developed a simple, standardized method to quantify lipid content of mouse thermogenic adipose tissue. This method, using FIJI analysis of hematoxylin/eosin stained sections, was highly objective and highly reproducible, with ∼99% inter-rater reliability. The method was compared to direct lipid staining of adipose tissue, with comparable results. We used our method to analyze perivascular adipose tissue (PVAT) from C57BL/6 mice on a normal chow diet, compared to calorie restriction or a high fat diet, where lipid storage phenotypes are known. Results indicate that lipid content can be estimated within mouse PVAT in a quantitative and reproducible manner, and shows correlation with previously studied molecular and physiological measures.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":"59 1","pages":"43-49"},"PeriodicalIF":1.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8766879/pdf/nihms-1726193.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10514590","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":"CIDEC: A Potential Factor in Diabetic Vascular Inflammation.","authors":"Fang-Qiang Song,&nbsp;Hui-Min Zhou,&nbsp;Wei-Xuan Ma,&nbsp;Yu-Lin Li,&nbsp;Bo-Ang Hu,&nbsp;Yuan-Yuan Shang,&nbsp;Zhi-Hao Wang,&nbsp;Ming Zhong,&nbsp;Wei Zhang,&nbsp;Yun Ti","doi":"10.1159/000520685","DOIUrl":"https://doi.org/10.1159/000520685","url":null,"abstract":"<p><p>Cell death-inducing DFF45-like effector C (CIDEC) is involved in diet-induced adipose inflammation. Whether CIDEC plays a role in diabetic vascular inflammation remains unclear. A type 2 diabetic rat model was induced by high-fat diet and low-dose streptozotocin. We evaluated its characteristics by metabolic tests, Western blot analysis of CIDEC and C1q/tumor necrosis factor-related protein-3 (CTRP3) expression, and histopathological analysis of aortic tissues. The diabetic group exhibited elevated CIDEC expression, aortic inflammation, and remodeling. To further investigate the role of CIDEC in the pathogenesis of aortic inflammation, gene silencing was used. With CIDEC gene silencing, CTRP3 expression was restored, accompanied with amelioration of insulin resistance, aortic inflammation, and remodeling in diabetic rats. Thus, the silencing of CIDEC is potent in mediating the reversal of aortic inflammation and remodeling, indicating that CIDEC may be a potential therapeutic target for vascular complications in diabetes.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":"59 2","pages":"114-123"},"PeriodicalIF":1.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39590337","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":"Contents, Vol. 59, 2022.","authors":"","doi":"10.1159/000528269","DOIUrl":"https://doi.org/10.1159/000528269","url":null,"abstract":"Ramaroson Andriantsitohaina – Université d’Angers, Angers, France Zoltan Bagi – Augusta University, Augusta, GA, USA Erika M. Boerman – University of Missouri School of Medicine, Columbia, MO, USA Georg Breier – Technische Universität Dresden, Dresden, Germany Jerome W. Breslin – University of South Florida, Tampa, FL, USA Nicola J. Brown – University of Sheffield, Sheffield, UK Albert Busch – Technische Universität Dresden, Dresden, Germany Paul D. Chantler – West Virginia University School of Medicine, Morgantown, WV, USA John C. Chappell – Virginia Tech, Fralin Biomedical Research Institute, Roanoke, VA, USA Geraldine Clough – University of Southampton, Southampton, UK JVR Journal of Vascular Research","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":"59 6","pages":"I-IV"},"PeriodicalIF":1.7,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10417904","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}