Arteriosclerosis, Thrombosis, and Vascular Biology最新文献

{"title":"From Adipose Immune Homeostasis to Atherosclerosis and Hepatic Steatosis: The Adipocyte MHCII-Treg Axis in Obesity.","authors":"Aida Javidan, Barbara S Nikolajczyk","doi":"10.1161/ATVBAHA.126.325469","DOIUrl":"10.1161/ATVBAHA.126.325469","url":null,"abstract":"","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13597141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148987758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sexually Dimorphic Role of Estrogen Receptor α in Preserving Right Ventricular Endothelial Integrity.","authors":"Jiajun Li, Vijaya Karoor, Andrea L Frump, Hanqiu Zhao, Shunning Liang, Chen-Shan Chen Woodcock, Irina Petrache, Zhiyu Dai, Tim Lahm","doi":"10.1161/ATVBAHA.126.325390","DOIUrl":"10.1161/ATVBAHA.126.325390","url":null,"abstract":"<p><strong>Background: </strong>Right ventricular (RV) adaptation to increased afterload determines survival in pulmonary hypertension (PH) and is sexually dimorphic and more preserved in females, mediated in part by protective ERα (estrogen receptor α) signaling in cardiomyocytes. However, effects of ERα on RV endothelial cells (RVECs), a critical mediator of RV adaptation, are unknown. We hypothesized that ERα exerts sexually dimorphic proangiogenic effects on RVECs in vitro and in vivo.</p><p><strong>Methods: </strong>We isolated RVECs from male and female rats with an ERα^Mut (ERα loss-of-function mutation) or wild-type controls and assessed angiogenesis end points. Male and female ERα^Mut or wild-type rats were treated with monocrotaline or underwent pulmonary arterial banding. Single-nucleus RNA sequencing was performed to investigate RVEC transcriptomic changes.</p><p><strong>Results: </strong>Compared with cells isolated from wild-type animals, RVECs from male and female ERα^Mut rats exhibited reduced ability to form pseudovascular networks, sprout, and migrate. RVECs from female ERα^Mut rats demonstrated increased apoptosis. Restoring migration rescued the impaired angiogenic phenotype in female ERα^Mut RVECs. Female monocrotaline-PH ERα^Mut rats exhibited increased RV hypertrophy and reduced RV capillary density before (10 days) and at the time of established PH (28 days). Female ERα^Mut pulmonary arterial banding rats also exhibited decreased RV capillary density. Capillary rarefaction was associated with decreased tip cell abundance and increased RVEC apoptosis, and a net loss of the endocardial RVEC subpopulation. Differentially expressed gene analysis and pathway analysis identified decreased expression of migration pathways and increased expression of apoptosis pathways in capillary and endocardial RVECs from female but not male monocrotaline-PH ERα^Mut rats.</p><p><strong>Conclusions: </strong>ERα exhibits a sex-specific endothelial-intrinsic role that is essential for RV angiogenesis under both homeostatic and pathological conditions. This effect appears to stem from enhanced survival and migration capacity of capillary and endocardial RVECs. ERα may be a potential target for sex-specific RV-directed therapies in PH.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148918353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell-to-Cell Signaling Networks at the Blood-Brain Barrier in Health and Disease.","authors":"Joseph H McCarty","doi":"10.1161/ATVBAHA.126.324590","DOIUrl":"10.1161/ATVBAHA.126.324590","url":null,"abstract":"<p><p>The blood-brain barrier (BBB) is a highly specialized interface between the central nervous system and the peripheral circulation, crucial for maintaining neuronal homeostasis and protecting the brain parenchyma from potentially harmful blood-borne substances. This review examines the molecular and cellular organization of the BBB and explores how defective cell adhesion and signaling networks lead to BBB pathologies. I discuss the intricate architecture of brain endothelial cells within the context of the larger multicellular neurovascular unit, highlighting the roles of pericytes, astrocytes, as well as ECM (extracellular matrix) proteins and growth factors in vascular basement membranes. Recent advances in understanding endothelial cell tight junction dynamics, transport mechanisms, and communication pathways within the neurovascular unit are presented, with a particular emphasis on astrocyte-endothelial communication. Furthermore, I detail how abnormal astrocyte-endothelial signaling leads to BBB breakdown and contributes to various neurological disorders. In summary, this review synthesizes current knowledge of BBB biology, with particular emphasis on recent discoveries in signaling pathways, intercellular adhesion, and dynamic regulatory mechanisms that govern barrier function. By integrating findings from functional studies across multiple models, this review provides critical insights into both fundamental BBB biology and the potential development of translational approaches for treating human cerebrovascular disorders. Understanding these complex mechanisms not only advances our knowledge of normal brain homeostasis but also illuminates promising therapeutic targets and strategies for addressing conditions ranging from stroke to neurodegenerative diseases, ultimately paving the way for more effective clinical interventions that can preserve or restore BBB integrity.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13544264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148878828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Thrombopoietin/MPL Signaling to Mitigate JAK2V617F-Driven Cardiac Microvascular Disease.","authors":"Xiaoxi Yang, Kyla Masarik, Xiaochuan Sun, Fangfang Zhang, Kirsten Zheng, Haoyi Zheng, Huichun Zhan","doi":"10.1161/ATVBAHA.126.325061","DOIUrl":"10.1161/ATVBAHA.126.325061","url":null,"abstract":"<p><strong>Background: </strong>Individuals with <i>JAK2V617F</i>-mutant myeloproliferative neoplasms or clonal hematopoiesis of indeterminate potential have a markedly increased risk of cardiovascular disease, yet the mechanisms by which mutant blood cells drive vascular and cardiac dysfunction remain incompletely understood. Although the thrombopoietin receptor MPL is central to hematopoiesis and is expressed in vascular endothelial cells (ECs), its role in JAK2V617F-associated cardiovascular complications is unknown.</p><p><strong>Methods: </strong>We generated chimeric mice with <i>JAK2V617F</i>-mutant blood cells and wild-type endothelium by bone marrow transplantation and challenged them with a high-fat/high-cholesterol diet to model cardiometabolic stress.</p><p><strong>Results: </strong>Mice with <i>JAK2V617F</i>-mutant blood cells developed a distinct cardiovascular phenotype characterized by microvascular disease, increased left ventricular mass, and relatively preserved left ventricular ejection fraction. Histopathologic analysis revealed coronary arteriole stenosis, perivascular fibrosis, reduced microvascular density, and endocardial injury, without evidence of epicardial coronary stenosis or myocardial infarction. Single-cell RNA sequencing revealed activation of inflammatory, stress-response, and endothelial-to-mesenchymal transition gene signatures in ECs, most prominently within the endocardial ECs. Immunohistochemistry identified MPL expression predominantly in endocardial ECs. Thrombopoietin/MPL signaling was upregulated in endocardial ECs in mice with <i>JAK2V617F</i>-mutant hematopoiesis, and treatment with an anti-MPL neutralizing antibody markedly improved cardiovascular pathology, restored endocardial integrity, and increased coronary microvascular density.</p><p><strong>Conclusions: </strong><i>JAK2V617F</i>-mutant hematopoiesis induces cardiac microvascular dysfunction under cardiometabolic stress. Endocardial ECs play a critical role in this pathological process, and endocardial MPL signaling constitutes a potential targetable pathway in JAK2V617F-associated cardiovascular disease.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13595420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148878818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scube2 Modulates Coronary Vessel Formation During Cardiac Growth and Regeneration in Zebrafish.","authors":"Ke-Hsuan Wei, Ann Nee Lee, Kaushik Chowdhury, Muhammad Abdul Rouf, An-Ju Chu, Yu-Jen Hung, Ku-Chi Tsao, Yan-Ting Chen, Yuh-Charn Lin, Edita Bakūnaitė, Yao-Ming Chang, Darius Balciunas, Rubén Marín-Juez, Ruey-Bing Yang, Shih-Lei Ben Lai","doi":"10.1161/ATVBAHA.126.324944","DOIUrl":"10.1161/ATVBAHA.126.324944","url":null,"abstract":"<p><strong>Background: </strong>Coronary vessel formation is essential for cardiac growth and regeneration, yet the extracellular mechanisms coordinating coronary vascular remodeling remain incompletely understood. Scube2 (signal peptide-CUB [complement C1r/C1s, Uegf, Bmp1 (bone morphogenetic protein 1)]-EGF domain-containing protein 2) has been implicated in developmental vascular signaling, but its role in coronary vessel formation and cardiac regeneration has not been established.</p><p><strong>Methods: </strong>We investigated Scube2 function using zebrafish genetic loss-of-function mutants, inducible global and epicardial-specific dominant-negative models, cryoinjury-induced cardiac regeneration, confocal and ultrastructural imaging, bulk RNA sequencing, and biochemical analyses to examine signaling mechanisms.</p><p><strong>Results: </strong>Scube2 was expressed in the epicardium under homeostatic conditions and was rapidly induced in epicardial-derived cells following cardiac injury. Loss of Scube2 impaired developmental coronary vessel formation and caused myocardial ultrastructural abnormalities. Following injury, Scube2 deficiency resulted in defective revascularization, reduced mural cell association, decreased endothelial and cardiomyocyte proliferation, persistent fibrosis, and impaired cardiac regeneration. Temporal and epicardial-specific inhibition of Scube2 recapitulated these regenerative defects. Transcriptomic analyses identified dysregulation of VEGF (vascular endothelial growth factor) and PDGF (platelet-derived growth factor) signaling pathways, accompanied by reduced endothelial proliferation and prolonged inflammatory responses. Mechanistically, SCUBE2 interacted with PDGF-B (PDGF subunit B) and PDGFRβ (PDGF receptor β) and enhanced PDGFRβ activation, supporting a role in endothelial-mural cell communication during vascular remodeling.</p><p><strong>Conclusions: </strong>Scube2 is a critical regulator of coronary vessel formation and regenerative revascularization in zebrafish. By promoting PDGF-dependent endothelial-mural cell interactions, Scube2 coordinates vascular remodeling that supports myocardial regeneration. These findings identify Scube2 as a previously unrecognized regulator of coronary vascularization and suggest extracellular modulation of PDGF signaling as a potential therapeutic strategy to enhance cardiac repair after ischemic injury.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"e324944"},"PeriodicalIF":8.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aortic Stenosis Hyalectan Remodeling Revealed by Proteomics and Glycoproteomics.","authors":"Siqi Yin, Ursula Mayr, Javier Barallobre-Barreiro, Elisa Duregotti, Anna K Barton, Rong Bing, Dyana Markose, Xiaoke Yin, Padmini Sarathchandra, Bhawana Singh, Wen-Yu Lin, Marika Fava, Lukas E Schmidt, Ferheen Baig, Ajay M Shah, Konstantinos Theofilatos, Najma Latif, Christian Hengstenberg, Tamás Radovits, Béla Merkely, Neil C Henderson, Marc R Dweck, Manuel Mayr","doi":"10.1161/ATVBAHA.126.323867","DOIUrl":"10.1161/ATVBAHA.126.323867","url":null,"abstract":"<p><strong>Background: </strong>Calcific aortic valve (AV) disease (CAVD) is recognized as an active pathological process involving extracellular matrix remodeling. This study investigates extracellular matrix remodeling through proteomic analysis and a novel mouse model of aortic stenosis.</p><p><strong>Methods: </strong>Proteomic and glycoproteomic analyses were conducted on AV leaflets from heart transplant donors (n=29) and patients with CAVD (n=17). Each CAVD sample was subdivided into noncalcified and calcified regions. To investigate the functional impact of extracellular matrix remodeling on aortic stenosis, we crossed apolipoprotein E-deficient mice (<i>ApoE</i>^<i>-/-</i>) with mice lacking the catalytic domain of ADAMTS5 (<i>Adamts5</i>^<i>Δcat</i>) to generate a mouse model combining hyalectan accumulation with hypercholesterolemia.</p><p><strong>Results: </strong>Proteomic and glycoproteomic analyses revealed hyalectan accumulation in CAVD compared with control valves. Versican predominated in noncalcified regions, while aggrecan was enriched in calcified regions. The shift in hyalectan composition correlated with changes in AV pressure gradient, elevated osteoblast-like cell markers, and inflammatory proteins, most notably pentraxin 3. Both versican and aggrecan are characterized by their ability to bind hyaluronan and serve as substrates of ADAMTS5. In <i>Adamts5</i>^<i>Δcat</i><i>/ApoE</i>^<i>-</i>^<i>/-</i> mice, hyalectan accumulation was associated with narrowed aortic cusp separation and increased post-AV velocity. Proteomic analysis of AVs from <i>Adamts5</i>^<i>Δcat</i><i>/ApoE</i>^<i>-</i>^<i>/-</i> mice revealed elevated versican, aggrecan, and pentraxin 3, recapitulating key features of human CAVD. Single-cell RNA sequencing and in vitro experiments linked versican to activated valve interstitial cells, while aggrecan colocalized with calcification markers in osteoblast-like cells. Pentraxin 3 was bound to hyaluronan and accumulated in calcified AVs. ADAMTS5 deficiency was sufficient to cause intact versican accumulation and promote valve interstitial cell activation, accompanied by increased expression of osteopontin. Osteopontin is a ligand of CD44, a principle hyaluronan receptor.</p><p><strong>Conclusions: </strong>This study highlights hyaluronan remodeling during aortic stenosis pathogenesis. A shift from versican to aggrecan in human CAVD correlates with changes in AV pressure gradient. In <i>Adamts5</i>^<i>Δcat</i><i>/ApoE</i>^<i>-</i>^<i>/-</i> mice, impaired hyalectan catabolism promotes aortic stenosis.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"e323867"},"PeriodicalIF":8.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13506200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Angiogenesis in Lung Regeneration and Aging.","authors":"Priscilla Kyi, Mikaela Scheer, Tadanori Mammoto, Akiko Mammoto","doi":"10.1161/ATVBAHA.126.324410","DOIUrl":"10.1161/ATVBAHA.126.324410","url":null,"abstract":"<p><p>Angiogenesis, the formation of new capillary blood vessels, plays a key role in organ development and regeneration, while its dysregulation contributes to disease pathogenesis. In addition to the passive roles of blood vessels in gas exchange and nutrient delivery, endothelial cells regulate tissue homeostasis by secreting angiocrine factors that dictate the behaviors of surrounding cells to build tissue architecture. In the lung, endothelial cells closely interact with alveolar epithelial cells and other resident cells to coordinate signals necessary for alveolar regeneration. During aging, impaired angiogenic responses diminish tissue regeneration and injury repair, increasing susceptibility to chronic lung diseases. In addition to biochemical signals, dynamic changes in the mechanical forces also regulate pulmonary angiogenesis. In this brief review, we highlight the mechanisms by which endothelial cells maintain vascular homeostasis in the lung and how these processes become dysregulated with aging. We also discuss the impact of changes in the micromechanical environment and summarize recently developed new approaches for investigating endothelial cell signaling and cell-cell interactions in the human lung, which leads to the development of future therapeutic strategies.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"e324410"},"PeriodicalIF":8.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13353207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tuning BMP-Regulated Cell Differentiation in the Aortic Media by Mutating Matrix Gla Protein.","authors":"Xinjiang Cai, Kavinda K J Gunasinghe, Lei Qi, Li Zhang, Xiuju Wu, Zheng Jing, Yan Zhao, Hannah Kim, Eddy Yao, Tzung K Hsiai, Taufiq Rahman, Xavier W Chee, Yucheng Yao, Kristina I Boström","doi":"10.1161/ATVBAHA.126.324621","DOIUrl":"10.1161/ATVBAHA.126.324621","url":null,"abstract":"<p><strong>Background: </strong>MGP (matrix Gla protein) serves as an inhibitor of vascular calcification by limiting elastin degradation and regulating BMP (bone morphogenetic protein) activity. Mutation of the conserved proline residue 64 to glycine in MGP abolishes BMP binding in vitro. We hypothesized that selective loss of BMP binding would elucidate the contribution of BMP to cell differentiation in <i>Mgp</i>-deficient mice.</p><p><strong>Methods: </strong>Computational analyses using AlphaFold3 and molecular dynamics simulations were performed to determine the structural effects of γ-carboxylation and the proline residue 64 to glycine mutation. The vascular phenotype of <i>Mgp</i>-knockin mice expressing the proline residue 64 to glycine mutation was compared with wild-type (WT) and global <i>Mgp</i>-knockout mice. Proximity ligation assay was performed to assess MGP-BMP4 in aortic cells. Single-cell RNA-sequencing was used to identify cellular alterations in the vascular media.</p><p><strong>Results: </strong>Molecular dynamics simulation revealed 5 Ca²⁺ ions coordinated by γ-carboxylated Glu residues in the MGP dimer. The proline residue 64 to glycine mutation did not disrupt Ca²⁺ binding but likely suppressed conformational changes required for BMP4 binding. Unlike <i>Mgp</i>-<i>KO</i> mice, <i>Mgp</i>-knockin mice did not develop vascular calcification, elastic lamina proteolysis, and endothelial-mesenchymal transition, but exhibited vascular fibrosis. MGP-BMP4 interaction observed in WT aortic cells was barely detectable in <i>Mgp</i>-knockin aortic cells. Single-cell RNA-sequencing revealed increased fractions of smooth muscle cells and enhanced myofibroblast differentiation in the <i>Mgp</i>-knockin aortas compared with WT. In <i>Mgp</i>-knockin aortas, SMAD2 expression was significantly increased throughout the vessel wall compared with WT aortas. In contrast, SMAD1/5/9 activation in the <i>Mgp</i>-knockout aortas was more confined to the endothelium, whereas it localized to the media-adventitia transition in WT and <i>Mgp</i>-knockin aortas. Both <i>Mgp</i>-knockin and <i>Mgp</i>-knockout mice developed arteriovenous malformations in the lungs, kidneys, and brain.</p><p><strong>Conclusions: </strong>Our findings suggest that MGP plays a versatile role in preserving vascular integrity, in part serving as an important BMP-trap aimed at directing vascular cell differentiation.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"e324621"},"PeriodicalIF":8.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13506195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelial Cell-Pericyte Crosstalk in the Brain Balances Microvascular Stability and Plasticity.","authors":"Jihui Lee, Emily Luc, Amber N Stratman","doi":"10.1161/ATVBAHA.126.323547","DOIUrl":"10.1161/ATVBAHA.126.323547","url":null,"abstract":"<p><p>Pericytes are mural cells that broadly support microvascular integrity and are essential contributors to the neurovascular unit in the brain. They contribute to blood-brain barrier function, endothelial behavior, and microvascular tone, and their dysfunction is implicated in cardiometabolic and neurovascular disease. However, pericytes remain difficult to directly manipulate due to heterogeneous identity, overlapping marker expression with other mural and stromal cells, and context-dependent functional behaviors. Here, we propose that pericytes are best understood as dynamic regulators of microvascular state rather than a static cell type. Pericyte behaviors span a spectrum of functional states associated with vascular stability, angiogenesis, contractility, and fibrosis, and transitions between these functions shape microvascular remodeling in development, homeostasis, and disease. In their stabilization state, pericytes support blood-brain barrier integrity and microvascular stability, and when disrupted, can contribute to small vessel disease and neurodegeneration. Conversely, a plastic pericyte state is often associated with angiogenesis and ischemia-reperfusion responses, but can also contribute to fibrotic remodeling. Finally, we discuss how experimental systems, including in vitro and in vivo models, inform the interpretation of pericyte function and state. This perspective provides a framework for interpreting pericyte biology in the context of endothelial cell function and suggests that targeting pericyte state dynamics may offer new opportunities to protect the microvasculature in response to cardiometabolic and neurovascular disease.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"e323547"},"PeriodicalIF":8.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13426066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 Myosin 2 Filaments Dynamically Assemble and Stabilize During Induced Contractility.","authors":"Sasha K Demeulenaere, Margaret A Bennett, Bradley Somerfield, Huini Wu, Margaret E Utgaard, Hiral Patel, Stefano Sala, Elizabeth R Longtine, Ahmed Zied, Jonathan A Kirk, Patrick W Oakes, Jordan R Beach","doi":"10.1161/ATVBAHA.126.324897","DOIUrl":"10.1161/ATVBAHA.126.324897","url":null,"abstract":"<p><strong>Background: </strong>Vascular smooth muscle cells (SMCs) dynamically tune blood vessel diameter to regulate blood pressure, provide vessel wall structural integrity, and absorb shock on a beat-to-beat timescale. SMII (smooth muscle myosin 2) is the dominant motor protein driving SMC contraction. To function, SMII monomers dynamically assemble into filaments, which associate with the actin cytoskeleton to drive contractility. Precisely how SMII filaments assemble and exchange in living SMCs, however, both at steady state and during induced contractility, remains poorly defined.</p><p><strong>Methods: </strong>We used a single-cell filament assembly assay to determine SMII assembly into filaments at steady state and upon induced contractility in rat aortic SMCs (A7r5) transiently expressing EGFP (enhanced green fluorescent protein)-tagged SM1A (SMII isoform 1A). We then used fluorescence recovery after photobleaching (FRAP) to characterize SMII exchange kinetics at steady state and upon induced contractility, and measured changes in force production using traction force microscopy. Finally, we developed a knock-in EGFP-SMII murine model to quantify SMII dynamics at endogenous expression in primary SMCs and intact arterioles.</p><p><strong>Results: </strong>While predominantly filamentous at baseline, induced contraction rapidly increased SMII filament assembly. Fluorescence recovery after photobleaching revealed rapid SMII exchange kinetics, more similar to nonmuscle myosin II than striated myosin II, and induced contractility consistently stabilized SMII filaments. Super-resolution imaging revealed SMII and nonmuscle myosin II filament structures consistent with coassembly. Endogenous EGFP-SMII in primary SMCs and intact arterioles paralleled cell culture studies with similar baseline exchange kinetics and activation-dependent stabilization.</p><p><strong>Conclusions: </strong>Together, these data support a model in which SMII is surprisingly dynamic and coassembles with nonmuscle myosin II. Vascular SMC activation further increases SMII filament assembly while reducing filament exchange, consistent with stabilization of a dynamic SMII pool during force generation, thereby allowing cells to dynamically adapt their overall contractility in response to environmental conditions.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"e324897"},"PeriodicalIF":8.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13506201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}