Vascular biology (Bristol, England)最新文献_第2页

Endothelial structure contributes to heterogeneity in brain capillary diameter. 内皮结构导致脑毛细血管直径的异质性。

Vascular biology (Bristol, England) Pub Date : 2023-09-06 Print Date: 2023-01-01 DOI: 10.1530/VB-23-0010

Sheridan M Sargent, Stephanie K Bonney, Yuandong Li, Stefan Stamenkovic, Marc M Takeno, Vanessa Coelho-Santos, Andy Y Shih

{"title":"Endothelial structure contributes to heterogeneity in brain capillary diameter.","authors":"Sheridan M Sargent, Stephanie K Bonney, Yuandong Li, Stefan Stamenkovic, Marc M Takeno, Vanessa Coelho-Santos, Andy Y Shih","doi":"10.1530/VB-23-0010","DOIUrl":"10.1530/VB-23-0010","url":null,"abstract":"The high metabolic demand of brain tissue is supported by a constant supply of blood flow through dense microvascular networks. Capillaries are the smallest class of vessels in the brain and their lumens vary in diameter between ~2 and 5 μm. This diameter range plays a significant role in optimizing blood flow resistance, blood cell distribution, and oxygen extraction. The control of capillary diameter has largely been ascribed to pericyte contractility, but it remains unclear if the architecture of the endothelial wall also contributes to capillary diameter. Here, we use public, large-scale volume electron microscopy data from mouse cortex (MICrONS Explorer, Cortical mm3) to examine how endothelial cell number, endothelial cell thickness, and pericyte coverage relates to microvascular lumen size. We find that transitional vessels near the penetrating arteriole and ascending venule are composed of two to six interlocked endothelial cells, while the capillaries intervening these zones are composed of either one or two endothelial cells, with roughly equal proportions. The luminal area and diameter are on average slightly larger with capillary segments composed of two interlocked endothelial cells vs one endothelial cell. However, this difference is insufficient to explain the full range of capillary diameters seen in vivo. This suggests that both endothelial structure and other influences, including pericyte tone, contribute to the basal diameter and optimized perfusion of brain capillaries.","PeriodicalId":75294,"journal":{"name":"Vascular biology (Bristol, England)","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10503221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10230954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The inhibition of Wnt signaling attenuates RANKL-induced osteoclastogenic macrophage activation. 抑制Wnt信号可减弱rankl诱导的破骨细胞巨噬细胞活化。

Vascular biology (Bristol, England) Pub Date : 2023-07-13 DOI: 10.1530/VB-23-0007

Dai Yamanouchi, Kimihiro Igari

{"title":"The inhibition of Wnt signaling attenuates RANKL-induced osteoclastogenic macrophage activation.","authors":"Dai Yamanouchi, Kimihiro Igari","doi":"10.1530/VB-23-0007","DOIUrl":"https://doi.org/10.1530/VB-23-0007","url":null,"abstract":"Abdominal aortic aneurysms (AAAs) have been linked to the activation of osteoclastogenic macrophages. Reports have suggested that Wnt signaling has a dual effect of proliferation and differentiation during osteoclastogenesis. The Wnt/β-Catenin pathway is a critical regulator of cell pluripotency, cell survival, and cell fate decisions. It regulates cell proliferation and differentiation through transcriptional co-activators, CBP, and p300, respectively. The inhibition of β-catenin suppresses proliferation but induces differentiation of osteoclast precursor cells. This study aimed to examine the effect of ICG-001, a β-catenin/CBP-specific Wnt signaling inhibitor, on osteoclastogenesis by inhibiting proliferation without inducing differentiation. To induce osteoclastogenesis, RAW 264.7 macrophages were stimulated with a soluble receptor activator of NF-κB ligand (RANKL). The effect of Wnt signaling inhibition was examined by treating macrophages with or without ICG-001 during RANKL stimulation. The activation and differentiation of macrophages were examined through western blotting, quantitative PCR, and tartrate-resistant acid phosphate (TRAP) staining in vitro. The relative expression level of the nuclear factor of activated T-cells cytoplasmic 1 protein was significantly suppressed by ICG-001 treatment. The relative expression levels of mRNA of TRAP, cathepsin K, and matrix metalloproteinase-9 were significantly lower in the ICG-001-treated group. The number of TRAP-positive cells decreased in the ICG-001-treated group relative to the non-treated group. The inhibition of Wnt signaling pathway via ICG-001 suppressed osteoclastogenic macrophage activation. Our previous studies have shown the importance of osteoclastogenic macrophage activation in AAA. Further research to examine the therapeutic potential of ICG-001 on AAA is warranted.","PeriodicalId":75294,"journal":{"name":"Vascular biology (Bristol, England)","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9a/34/VB-23-0007.PMC10390850.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10107816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

SLC20a1/PiT-1 is required for chorioallantoic placental morphogenesis. 绒毛膜胎盘形态发生需要SLC20a1/PiT-1。

Vascular biology (Bristol, England) Pub Date : 2023-04-19 Print Date: 2023-04-01 DOI: 10.1530/VB-22-0018

Ana Correia-Branco, Ariel Mei, Sreehari Pillai, Nirmala Jayaraman, Radhika Sharma, Alison G Paquette, Naveen K Neradugomma, Ciara Benson, Nicholas W Chavkin, Qingcheng Mao, Mary C Wallingford

{"title":"SLC20a1/PiT-1 is required for chorioallantoic placental morphogenesis.","authors":"Ana Correia-Branco, Ariel Mei, Sreehari Pillai, Nirmala Jayaraman, Radhika Sharma, Alison G Paquette, Naveen K Neradugomma, Ciara Benson, Nicholas W Chavkin, Qingcheng Mao, Mary C Wallingford","doi":"10.1530/VB-22-0018","DOIUrl":"10.1530/VB-22-0018","url":null,"abstract":"The placenta mediates the transport of nutrients, such as inorganic phosphate (Pi), between the maternal and fetal circulatory systems. The placenta itself also requires high levels of nutrient uptake as it develops to provide critical support for fetal development. This study aimed to determine placental Pi transport mechanisms using in vitro and in vivo models. We observed that Pi (P33) uptake in BeWo cells is sodium dependent and that SLC20A1/Slc20a1 is the most highly expressed placental sodium-dependent transporter in mouse (microarray), human cell line (RT-PCR) and term placenta (RNA-seq), supporting that normal growth and maintenance of the mouse and human placenta requires SLC20A1/Slc20a1. Slc20a1 wild-type (Slc20a1+/+) and knockout (Slc20a1-/-) mice were produced through timed intercrosses and displayed yolk sac angiogenesis failure as expected at E10.5. E9.5 tissues were analyzed to test whether placental morphogenesis requires Slc20a1. At E9.5, the developing placenta was reduced in size in Slc20a1-/-. Multiple structural abnormalities were also observed in the Slc20a1-/-chorioallantois. We determined that monocarboxylate transporter 1 protein (MCT1+) cells were reduced in developing Slc20a1-/-placenta, confirming that Slc20a1 loss reduced trophoblast syncytiotrophoblast 1 (SynT-I) coverage. Next, we examined the cell type-specific Slc20a1 expression and SynT molecular pathways in silico and identified Notch/Wnt as a pathway of interest that regulates trophoblast differentiation. We further observed that specific trophoblast lineages express Notch/Wnt genes that associate with endothelial cell tip-and-stalk cell markers. In conclusion, our findings support that Slc20a1 mediates the symport of Pi into SynT cells, providing critical support for their differentiation and angiogenic mimicry function at the developing maternal-fetal interface.","PeriodicalId":75294,"journal":{"name":"Vascular biology (Bristol, England)","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c2/ef/VB-22-0018.PMC10160536.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9771831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

BEYOND THE ENDOTHELIUM: THE ROLE OF MURAL CELLS IN VASCULAR BIOLOGY: In vitro systems to study endothelial/pericyte cell interactions. 超越内皮:壁细胞在血管生物学中的作用:研究内皮/周细胞相互作用的体外系统。

Vascular biology (Bristol, England) Pub Date : 2023-02-01 DOI: 10.1530/VB-22-0021

Emily Warren, Sharon Gerecht

{"title":"BEYOND THE ENDOTHELIUM: THE ROLE OF MURAL CELLS IN VASCULAR BIOLOGY: In vitro systems to study endothelial/pericyte cell interactions.","authors":"Emily Warren, Sharon Gerecht","doi":"10.1530/VB-22-0021","DOIUrl":"https://doi.org/10.1530/VB-22-0021","url":null,"abstract":"The vasculature is crucial for tissue development and survival, and the stability of blood vessels to perform these functions relies on the interplay between endothelial cells (ECs) and mural cells. Pericytes are a subtype of mural cells found in the microvasculature that extend their processes to wrap around the endothelial monolayer. Pericytes are recruited during vessel growth through the excretion of soluble factors from ECs where they stabilize angiogenic sprouts and induce maturation of the resident cells. Alterations in these interactions between ECs and pericytes are associated with aberrant vessel growth and disrupted vasculature function characteristic of numerous diseases. Therefore, deeper understanding of the cross-talk between these cell types has numerous implications for understanding morphogenesis and elucidating disease mechanisms. In this review, we highlight recent advances and current trends studying the interactions between ECs and pericytes in vitro. We begin by analyzing three-dimensional hydrogel platforms that mimic the tissue extracellular matrix to investigate signaling pathways and altered vascular function in disease-specific cells. We next examine how microfluidic vasculature-on-a-chip platforms have elucidated the interplay of these vascular cells during angiogenesis and vascular network formation under controlled physiochemical cues and interstitial flow. Additionally, studies have utilized microvessels to measure the effect of shear stress on barrier function through the control of luminal flow and the impact of inflammation on these vascular cell interactions. Finally, we briefly highlight self-assembling human blood vessel organoids, an emerging high-throughput platform to study ECs and pericyte interactions.","PeriodicalId":75294,"journal":{"name":"Vascular biology (Bristol, England)","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9989888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9320732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Should aspirin be replaced with ADP blockers and anti-GPVI to manage thrombosis? 是否应该用ADP阻滞剂和抗gpvi替代阿司匹林来控制血栓形成?

Vascular biology (Bristol, England) Pub Date : 2023-01-27 Print Date: 2023-01-01 DOI: 10.1530/VB-22-0010

Hafsa Khan, Tahira Ghulam, Naseer Ahmed, Muhammad Rafai Babar, Simon Dj Calaminus, Muhammad Zuhair Yusuf

{"title":"Should aspirin be replaced with ADP blockers and anti-GPVI to manage thrombosis?","authors":"Hafsa Khan, Tahira Ghulam, Naseer Ahmed, Muhammad Rafai Babar, Simon Dj Calaminus, Muhammad Zuhair Yusuf","doi":"10.1530/VB-22-0010","DOIUrl":"10.1530/VB-22-0010","url":null,"abstract":"Platelets have a pivotal role in maintaining cardiovascular homeostasis. They are kept docile by endothelial-derived mediators. Aberration in haemostatic balance predisposes an individual to an elevated risk of a prothrombotic environment. Anti-platelet therapy has been a key component to reduce this risk. However, understanding how these medications affect the balance between the activation and inhibition of platelets is critical. There is no evidence that a key anti-platelet therapy - aspirin, may not be the most efficacious medicine of choice, as it can compromise both platelet inhibition and activation pathways. In this review, the rationale of aspirin as an anti-thrombotic drug has been critically discussed. This review looks at how recently published trials are raising key questions about the efficacy and safety of aspirin in countering cardiovascular diseases. There is an increasing portfolio of evidence that identifies that although aspirin is a very cheap and accessible drug, it may be used in a manner that is not always beneficial to a patient, and a more nuanced and targeted use of aspirin may increase its clinical benefit and maximize patient response. The questions about the use of aspirin raise the potential for changes in its clinical use for dual anti-platelet therapy. This highlights the need to ensure that treatment is targeted in the most effective manner and that other anti-platelet therapies may well be more efficacious and beneficial for CVD patients in their standard and personalized approaches.","PeriodicalId":75294,"journal":{"name":"Vascular biology (Bristol, England)","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9986383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41457753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Vinculin strengthens the endothelial barrier during vascular development. 血管蛋白在血管发育过程中增强内皮屏障。

Vascular biology (Bristol, England) Pub Date : 2023-01-01 DOI: 10.1530/VB-22-0012

Miesje M van der Stoel, Maria P Kotini, Rianne M Schoon, Markus Affolter, Heinz-Georg Belting, Stephan Huveneers

{"title":"Vinculin strengthens the endothelial barrier during vascular development.","authors":"Miesje M van der Stoel, Maria P Kotini, Rianne M Schoon, Markus Affolter, Heinz-Georg Belting, Stephan Huveneers","doi":"10.1530/VB-22-0012","DOIUrl":"https://doi.org/10.1530/VB-22-0012","url":null,"abstract":"Remodelling of cell-cell junctions is crucial for proper tissue development and barrier function. The cadherin-based adherens junctions anchor via β-catenin and α-catenin to the actomyosin cytoskeleton, together forming a junctional mechanotransduction complex. Tension-induced conformational changes in the mechanosensitive α-catenin protein induce junctional vinculin recruitment. In endothelial cells, vinculin protects the remodelling of VE-cadherin junctions. In this study, we have addressed the role of vinculin in endothelial barrier function in the developing vasculature. In vitro experiments, using endothelial cells in which α-catenin was replaced by a vinculin-binding-deficient mutant, showed that junctional recruitment of vinculin promotes endothelial barrier function. To assess the role of vinculin within blood vessels in vivo, we next investigated barrier function in the vasculature of vcl knockout zebrafish. In the absence of vinculin, sprouting angiogenesis and vessel perfusion still occurred. Intriguingly, the absence of vinculin made the blood vessels more permeable for 10 kDa dextran molecules but not for larger tracers. Taken together, our findings demonstrate that vinculin strengthens the endothelial barrier and prevents vascular leakage in developing vessels.","PeriodicalId":75294,"journal":{"name":"Vascular biology (Bristol, England)","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/87/b0/VB-22-0012.PMC9986378.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10858817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Intercellular adhesion molecule 2 regulates diapedesis hotspots by allowing neutrophil crawling against the direction of flow. 细胞间粘附分子2通过允许中性粒细胞逆流动方向爬行来调节浸没热点。

Vascular biology (Bristol, England) Pub Date : 2023-01-01 DOI: 10.1530/VB-23-0005

Max L B Grönloh, Merel Elisabeth Tebbens, Marianthi Kotsi, Janine J G Arts, Jaap D van Buul

{"title":"Intercellular adhesion molecule 2 regulates diapedesis hotspots by allowing neutrophil crawling against the direction of flow.","authors":"Max L B Grönloh, Merel Elisabeth Tebbens, Marianthi Kotsi, Janine J G Arts, Jaap D van Buul","doi":"10.1530/VB-23-0005","DOIUrl":"https://doi.org/10.1530/VB-23-0005","url":null,"abstract":"Intercellular adhesion molecules (ICAMs) are cell surface proteins that play a crucial role in the body's immune response and inflammatory processes. ICAM1 and ICAM2 are two ICAM family members expressed on the surface of various cell types, including endothelial cells. They mediate the interaction between immune cells and endothelial cells, which are critical for the trafficking of leukocytes across the blood vessel wall during inflammation. Although ICAM1 plays a prominent role in the leukocyte extravasation cascade, it is less clear if ICAM2 strengthens ICAM1 function or has a separate function in the cascade. With CRISPR-)Cas9 technology, endothelial cells were depleted for ICAM1,ICAM2, or both, and we found that neutrophils favored ICAM1 over ICAM2 to adhere to. However, the absence of only ICAM2 resulted in neutrophils that were unable to find the transmigration hotspot, i.e. the preferred exit site. Moreover, we found that ICAM2 deficiency prevented neutrophils to migrate against the flow. Due to this deficiency, we concluded that ICAM2 helps neutrophils find the preferred exit sites and thereby contributes to efficient leukocyte extravasation.","PeriodicalId":75294,"journal":{"name":"Vascular biology (Bristol, England)","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10503216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10616542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

No prominent role for complement C1-esterase inhibitor in Marfan syndrome mice. 补体c1酯酶抑制剂对马凡氏综合征小鼠无明显作用。

Vascular biology (Bristol, England) Pub Date : 2022-11-30 Print Date: 2022-11-01 DOI: 10.1530/VB-22-0016

Stijntje Hibender, Siyu Li, Alex V Postma, Myrthe E Hoogeland, Denise Klaver, Richard B Pouw, Hans W Niessen, Antoine Hg Driessen, David R Koolbergen, Carlie Jm de Vries, Marieke Jh Baars, Arjan C Houweling, Paul A Krijnen, Vivian de Waard

{"title":"No prominent role for complement C1-esterase inhibitor in Marfan syndrome mice.","authors":"Stijntje Hibender, Siyu Li, Alex V Postma, Myrthe E Hoogeland, Denise Klaver, Richard B Pouw, Hans W Niessen, Antoine Hg Driessen, David R Koolbergen, Carlie Jm de Vries, Marieke Jh Baars, Arjan C Houweling, Paul A Krijnen, Vivian de Waard","doi":"10.1530/VB-22-0016","DOIUrl":"10.1530/VB-22-0016","url":null,"abstract":"Marfan syndrome (MFS) is a connective tissue disorder causing aortic aneurysm formation. Currently, only prophylactic aortic surgery and blood pressure-lowering drugs are available to reduce the risk of aortic rupture. Upon whole genome sequencing of a Marfan family, we identified a complement gene C1R variant (p.Ser152Leu), which is associated with severe aortic patients. Therefore, we assessed the role of complement activation in MFS aortic tissue. Expression of various complement genes and proteins was detected in human and murine MFS aneurysm tissue, which prompted us to study complement inhibition in MFS mice. Treatment of the Fbn1C1041G/+ MFS mice with human plasma-derived C1-esterase inhibitor Cetor® resulted in reduced complement deposition, decreased macrophage influx in the aorta, and lower circulating TNFα levels. However, in line with previous anti-inflammatory treatments, complement inhibition did not change the aortic dilatation rate in this MFS mouse model. Thus, while complement factors/component 3 activation were detected in human/murine MFS aorta, Cetor® had no effect on aortic dilatation in MFS mice, indicating that complement inhibition is not a suitable treatment strategy in MFS.","PeriodicalId":75294,"journal":{"name":"Vascular biology (Bristol, England)","volume":" ","pages":"40-49"},"PeriodicalIF":0.0,"publicationDate":"2022-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9782404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10478286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cell contractility and focal adhesion kinase control circumferential arterial stiffness. 细胞收缩性和局灶黏附激酶控制周动脉硬度。

Vascular biology (Bristol, England) Pub Date : 2022-11-30 Print Date: 2022-11-01 DOI: 10.1530/VB-22-0013

Emilia Roberts, Tina Xu, Richard Assoian

{"title":"Cell contractility and focal adhesion kinase control circumferential arterial stiffness.","authors":"Emilia Roberts, Tina Xu, Richard Assoian","doi":"10.1530/VB-22-0013","DOIUrl":"10.1530/VB-22-0013","url":null,"abstract":"Arterial stiffening is a hallmark of aging and cardiovascular disease. While it is well established that vascular smooth muscle cells (SMCs) contribute to arterial stiffness by synthesizing and remodeling the arterial extracellular matrix, the direct contributions of SMC contractility and mechanosensors to arterial stiffness, and particularly the arterial response to pressure, remain less well understood despite being a long-standing question of biomedical importance. Here, we have examined this issue by combining the use of pressure myography of intact carotid arteries, pharmacologic inhibition of contractility, and genetic deletion of SMC focal adhesion kinase (FAK). Biaxial inflation-extension tests performed at physiological pressures showed that acute inhibition of cell contractility with blebbistatin or EGTA altered vessel geometry and preferentially reduced circumferential, as opposed to axial, arterial stiffness in wild-type mice. Similarly, genetic deletion of SMC FAK, which attenuated arterial contraction to KCl, reduced vessel wall thickness and circumferential arterial stiffness in response to pressure while having minimal effect on axial mechanics. Moreover, these effects of FAK deletion were lost by treating arteries with blebbistatin or by inhibiting myosin light-chain kinase. The expression of arterial fibrillar collagens, the integrity of arterial elastin, or markers of SMC differentiation were not affected by the deletion of SMC FAK. Our results connect cell contractility and SMC FAK to the regulation of arterial wall thickness and directionally specific arterial stiffening.","PeriodicalId":75294,"journal":{"name":"Vascular biology (Bristol, England)","volume":" ","pages":"28-39"},"PeriodicalIF":0.0,"publicationDate":"2022-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/50/d7/VB-22-0013.PMC9782408.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10548828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Molecular mechanisms and effects of urocortin II on rat adventitial fibroblast calcification induced by calcified medium. 尿皮质素II对钙化培养基诱导的大鼠外膜成纤维细胞钙化的分子机制和作用。

Vascular biology (Bristol, England) Pub Date : 2022-09-30 Print Date: 2022-09-01 DOI: 10.1530/VB-22-0006

Xusheng Zhang, Zhanjun Huang, Xiaorong Fan, Xiaoqing Tan, Chengzhi Lu, Jianshe Yang

{"title":"Molecular mechanisms and effects of urocortin II on rat adventitial fibroblast calcification induced by calcified medium.","authors":"Xusheng Zhang, Zhanjun Huang, Xiaorong Fan, Xiaoqing Tan, Chengzhi Lu, Jianshe Yang","doi":"10.1530/VB-22-0006","DOIUrl":"10.1530/VB-22-0006","url":null,"abstract":"The present study aimed to assess the role of urocortin II (UII) in the process of vascular calcification in vitro by using a calcification model, to detect the changes in the mRNA and protein levels of associated markers in rat adventitial fibroblasts (AFs) during their phenotypic transformation to osteoblast cellsto clarify the main signal transduction pathway of UII responsible for regulating vascular calcification and AF phenotypic transformation of osteoblast cells, and to prove that UII was an endogenous factor promoting vascular calcification, so as to provide an effective experimental basis for the clinical regulation of related diseases caused by vascular calcification. Finally, we successfully constructed the calcified cell model, found that UII was an endogenous substance regulating vascular calcification, regulated the vascular calcification by promoting apoptosis and inhibiting autophagy through up- and downregulated BAX and BCL-2/BECLIN 1 (BECN1) level, and the Wnt/β-catenin signaling pathway was involved.","PeriodicalId":75294,"journal":{"name":"Vascular biology (Bristol, England)","volume":" ","pages":"19-27"},"PeriodicalIF":0.0,"publicationDate":"2022-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f2/39/VB-22-0006.PMC9579898.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33455901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1