scholarly journals Vascular smooth muscle cells in atherosclerosis: time for a re-assessment

2021 ◽  
Author(s):  
Mandy O J Grootaert ◽  
Martin R Bennett
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Atherosclerotic Lesion ◽  
Muscle Cells ◽  
Lineage Tracing ◽  
Phenotypic Switching ◽  
Fibrous Cap ◽  
The Media

Abstract Vascular smooth muscle cells (VSMCs) are key participants in both early and late-stage atherosclerosis. VSMCs invade the early atherosclerotic lesion from the media, expanding lesions, but also forming a protective fibrous cap rich in extracellular matrix to cover the ‘necrotic’ core. Hence, VSMCs have been viewed as plaque-stabilizing, and decreased VSMC plaque content—often measured by expression of contractile markers—associated with increased plaque vulnerability. However, the emergence of lineage-tracing and transcriptomic studies has demonstrated that VSMCs comprise a much larger proportion of atherosclerotic plaques than originally thought, demonstrate multiple different phenotypes in vivo, and have roles that might be detrimental. VSMCs down-regulate contractile markers during atherosclerosis whilst adopting alternative phenotypes, including macrophage-like, foam cell-like, osteochondrogenic-like, myofibroblast-like, and mesenchymal stem cell-like. VSMC phenotypic switching can be studied in tissue culture, but also now in the media, fibrous cap and deep-core region, and markedly affects plaque formation and markers of stability. In this review, we describe the different VSMC plaque phenotypes and their presumed cellular and paracrine functions, the regulatory mechanisms that control VSMC plasticity, and their impact on atherogenesis and plaque stability.

scholarly journals Neointimal remodeling in carotid atherosclerosis: roles of matrix metalloproteinases-2 and -9 and different phenotypes of vascular smooth muscle cells

2020 ◽  
pp. 20-30
Author(s):  
Л.А. Богданов ◽  
Е.А. Великанова ◽  
Д.К. Шишкова ◽  
А.Р. Шабаев ◽  
А.Г. Кутихин
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Smooth Muscle Actin ◽  
Muscle Cells ◽  
Atherosclerotic Plaques ◽  
Double Positive ◽  
Fibrous Cap ◽  
The Media

Цель исследования - изучение распространенности и локализации сосудистых гладкомышечных клеток (СГМК) различного фенотипа в составе атеросклеротических бляшек сонной артерии, а также взаимосвязи различных клеточных популяций неоинтимы с экспрессией матриксных металлопротеиназ (ММП)-2 и ММП-9 в зависимости от степени стабильности бляшки. Методы. Проведено иммуногистохимическое исследование 16 атеросклеротических бляшек (8 клинически нестабильных и 8 стабильных), полученных при каротидной эндартерэктом в связи с гемодинамически значимым стенозом. Оценка сократительной способности СГМК проводилась при использовании метода иммуногистохимического типирования альфа-актина гладких мышц (α-SMA), синтетического, макрофагального и остеогенного фенотипов СГМК посредством типирования виметина, СВ68 и RUNX2 соответственно. Активность ремоделирования определялась посредством выявления ММП-2 и ММП-9. Результаты. Показано, что около трети каротидных бляшек характеризовались высокой экспрессией MMП-9 CD68-положительными клетками, что не коррелировало с их нестабильностью. Локализация, содержание и соотношение СГМК различного фенотипа и макрофагов значительно варьировали в зависимости от бляшки. Общей закономерностью было преимущественное послойное типирование на α-SMA в зоне интактных эластических волокон медии и, реже, в фиброзной покрышке или прилегающих участках. CD68-положительные клетки визуализировались в толще неоинтимы; некоторая их доля была колокализована с α-SMA, отражая СГМК макрофагального фенотипа. Положительное реакция на виментин наблюдалась на границе с эластическими волокнами медии, либо с основной клеточной массой неоинтимы и характеризовалась прилегающим бесклеточным экстрацеллюлярным матриксом, что свидетельствовало об активном синтезе его соответствующими клетками. Также в неоинтиме обнаруживались клетки положительные как на RUNX2 и α-SMA, так и исключительно RUNX2-положительные клетки. Заключение. Каротидные атеросклеротические бляшки характеризуются различной локализацией, содержанием и соотношением СГМК сократительного, синтетического, макрофагального и остеогенного фенотипов, при этом экспрессия ММП-2 и ММП-9 была ограничена CD68-положительными макрофагами и СГМК макрофагального фенотипа. Aim.To study prevalence and localization of different phenotypes of vascular smooth muscle cells (VSMCs) in carotid atherosclerotic plaques and to examine expression of matrix metalloproteinase (MMP)-2 and MMP-9 in relation to different cell populations within the neointima. Methods. The immunohistochemical examination was performed on 16 atherosclerotic plaques (8 unstable and 8 stable) excised during carotid endarterectomy for critical stenosis. VSMCs of contractile, synthetic, macrophagic, and osteogenic phenotypes were identified by staining for α-smooth muscle actin (α-SMA), vimentin, CD68, and RUNX2, respectively. Activity of neointimal remodeling was assessed by staining for MMP-2 and MMP-9. Results. Approximately one-third of atherosclerotic plaques was positively stained for MMP-9 exclusively expressed in CD68-positive cells, which however, did not correlate with plaque ruptures. Localization, content, and ratio of different VSCM phenotypes significantly varied in different plaques. Positive α-SMA staining was found mainly in the intact media and fibrous cap. In contrast, both CD68-positive and CD68/α-SMA double-positive cells were detected within the neointima but not in the media. Vimentin was expressed in the neointima between the medial layers and fibrous cap near the acellular extracellular matrix suggesting its active production by mesenchymal cells. Both RUNX2- and RUNX2 α-SMA double-positive cells indicative of VSMC osteogenic differentiation were also observed in the neointima. Conclusion. Carotid atherosclerotic plaques contained VSMCs of all phenotypes, which were differentially localized within the neointima; however, the MMP-2 and MMP-9 expression was restricted to CD68-positive macrophages and CD68/α-SMA-positive VSMCs of the macrophagal phenotype.

scholarly journals TRPC6 regulates phenotypic switching of vascular smooth muscle cells through plasma membrane potential‐dependent coupling with PTEN

2019 ◽  
Vol 33 (9) ◽  
pp. 9785-9796 ◽  
Author(s):  
Takuro Numaga‐Tomita ◽  
Tsukasa Shimauchi ◽  
Sayaka Oda ◽  
Tomohiro Tanaka ◽  
Kazuhiro Nishiyama ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Plasma Membrane ◽  
Membrane Potential ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Phenotypic Switching ◽  
Plasma Membrane Potential

Micro-RNA Regulation of Vascular Smooth Muscle Cells and Its Significance in Cardiovascular Diseases

2021 ◽  
Author(s):  
Duong Ngoc Diem Nguyen ◽  
William M Chilian ◽  
Shamsul Mohd Zain ◽  
Muhammad Fauzi Daud ◽  
Yuh Fen Pung
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Intracellular Signaling ◽  
Neointimal Hyperplasia ◽  
Muscle Cells ◽  
Micro Rna ◽  
Phenotypic Switching ◽  
Micro Rnas

Cardiovascular disease (CVD) is among the leading causes of death worldwide. Micro-RNAs (miRNAs), regulatory molecules that repress protein expression, have attracted considerable attention in CVD research. The vasculature plays a big role in CVD development and progression and dysregulation of vascular cells underlies the root of many vascular diseases. This review provides a brief introduction of the biogenesis of miRNAs and exosomes, followed by overview of the regulatory mechanisms of miRNAs in vascular smooth muscle cells (VSMCs) intracellular signaling during phenotypic switching, senescence, calcification and neointimal hyperplasia. Evidence of extracellular signaling of VSMCs and other cells via exosomal and circulating miRNAs was also presented. Lastly, current drawbacks and limitations of miRNA studies in CVD research and potential ways to overcome these disadvantages were discussed in detail. In-depth understanding of VSMC regulation via miRNAs will add substantial knowledge and advance research in diagnosis, disease progression and/or miRNA-derived therapeutic approaches in CVD research.

Expression and function of periostin-like factor in vascular smooth muscle cells

2007 ◽  
Vol 292 (5) ◽  
pp. C1672-C1680 ◽  
Author(s):  
Judith Litvin ◽  
Xing Chen ◽  
Sheri Keleman ◽  
Shimei Zhu ◽  
Michael Autieri
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Clinical Manifestations ◽  
Muscle Cells ◽  
Antibody Treatment ◽  
The Media ◽  
Vascular Proliferative Diseases ◽  
And Function

In injured blood vessels activated vascular smooth muscle cells (VSMCs) migrate from the media to the intima, proliferate and synthesize matrix proteins. This results in occlusion of the lumen and detrimental clinical manifestations. We have identified a novel isoform of the periostin family of proteins referred to as periostin-like factor (PLF). PLF expression in VSMCs was increased following treatment with mitogenic compounds, suggesting that PLF plays a role in VSMC activation. Correspondingly, proliferation of the cells was significantly reduced with anti-PLF antibody treatment. PLF expression increased VSMC migration, an essential cellular process leading to vascular restenosis after injury. PLF protein was localized to neointimal VSMC of rat and swine balloon angioplasty injured arteries, as well as in human arteries with transplant restenosis, supporting the hypothesis that PLF is involved in VSMC activation and vascular proliferative diseases. Taken together, these data suggest a role for PLF in the regulation of vascular proliferative disease.

scholarly journals MicroRNA regulation of BMP signaling; cross-talk between endothelium and vascular smooth muscle cells

2018 ◽  
Author(s):  
Charlene Watterston ◽  
Lei Zeng ◽  
Abidemi Onabadejo ◽  
Sarah J Childs
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Vascular Function ◽  
Muscle Cells ◽  
Phenotypic Switching ◽  
Vascular Stability ◽  
Bmp Signalling

AbstractVascular smooth muscle cells (vSMC) are essential to the integrity of blood vessels, and therefore an attractive target of therapeutics aimed at improving vascular function. Smooth muscle cells are one of the few cell types that maintain plasticity and can switch phenotypes from differentiated (contractile) to de-differentiated (synthetic) and vice versa. As small regulatory transcripts, miRNAs act as genetic ‘fine tuners’ of posttranscriptional events and can act as genetic switches promoting phenotypic switching. The microRNAmiR26atargets the BMP signalling effector,smad1. We show that loss ofmiR26leads to hemorrhage (a loss of vascular stability)in vivo, suggesting altered vascular differentiation. Reduction inmiR26alevels increasessmad1mRNA and phospho-Smad1 (pSmad1) levels. We show that increasing BMP signalling by overexpression ofsmad1also leads to hemorrhage and that normalization of Smad1 levels through double knockdown ofmiR26andsmad1rescues hemorrhage suggesting a direct relationship betweenmiR26andsmad1and vascular stability. Using a BMP genetic reporter and pSmad1 staining we show that the effect ofmiR26on vascular instability is non-autonomous; BMP signalling is active in embryonic endothelial cells, but not in smooth muscle cells. Nonetheless, increased BMP signalling due to loss ofmiR26results in an increase inacta2-expressing smooth muscle cell numbers and promotes a differentiated smooth muscle morphology. Taken together our data suggests thatmiR26modulates BMP signalling in endothelial cells and indirectly promotes a differentiated smooth muscle phenotype. Our data also suggests that crosstalk from BMP-responsive endothelium to smooth muscle is important for its differentiation.

scholarly journals Akt/eNOS and MAPK Signaling Pathways Mediated the Phenotypic Switching of Thoracic Aorta Vascular Smooth Muscle Cells in Aging/Hypertensive Rats

2018 ◽  
pp. 543-553 ◽  
Author(s):  
L. ZHANG ◽  
Z. XU ◽  
Y. WU ◽  
J. LIAO ◽  
F. ZENG ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Western Blot ◽  
Smooth Muscle Cells ◽  
Thoracic Aorta ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Mapk Signaling ◽  
Phenotypic Switching ◽  
Hypertensive Rats

Considerable evidence demonstrates that phenotypic switching of vascular smooth muscle cells (VSMCs) is influenced by aging and hypertension. During phenotypic switching, VSMCs undergo a switch to a proliferative and migratory phenotype, with this switch being a common pathology in cardiovascular diseases. The aim of this study was to explore the joint influence of age and hypertension on thoracic aortic smooth muscle phenotypic switching and the balance of Akt and mitogen-activated protein kinase (MAPK) signaling during this switch. Different ages of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were used to establish hypertension and aging models. The phenotypic state was determined by detecting the marker proteins α-SM-actin, calponin, and osteopontin (OPN) via immunohistochemical staining and Western blot. Signaling proteins associated with the Akt and MAPK pathways were detected in rat thoracic aorta using Western blot. Both aging and hypertension caused a decrease in contractile (differentiated) phenotype markers (α-SM-actin and calponin), while the synthetic (proliferative or de-differentiated) phenotype maker was elevated (OPN). When combining hypertension and aging, this effect was enhanced, with Akt signaling decreased, while MAPK signaling was increased. These results suggested that VSMCs phenotype switching is modulated by a balance between Akt and MAPK signaling in the process of aging and hypertension.

Sign in / Sign up

Export Citation Format

Share Document