scholarly journals S100B is required for maintaining an intermediate state with double-positive Sca-1+ progenitor and vascular smooth muscle cells during neointimal formation

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Yan Wu ◽  
Xin Liu ◽  
Ling-Yun Guo ◽  
Lei Zhang ◽  
Fei Zheng ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Progenitor Cells ◽  
Vascular Smooth Muscle Cells ◽  
Intermediate State ◽  
Muscle Cells ◽  
Neointimal Formation ◽  
Double Positive ◽  
Vessel Injury

Abstract Introduction Accumulation of vascular smooth muscle cells (VSMCs) within the neointimal region is a hallmark of atherosclerosis and vessel injury. Evidence has shown that Sca-1-positive (Sca-1+) progenitor cells residing in the vascular adventitia play a crucial role in VSMC assemblages and intimal lesions. However, the underlying mechanisms, especially in the circumstances of vascular injury, remain unknown. Methods and results The neointimal formation model in rats was established by carotid artery balloon injury using a 2F-Forgaty catheter. Most Sca-1+ cells first appeared at the adventitia of the vascular wall. S100B expressions were highest within the adventitia on the first day after vessel injury. Along with the sequentially increasing trend of S100B expression in the intima, media, and adventitia, respectively, the numbers of Sca-1+ cells were prominently increased at the media or neointima during the time course of neointimal formation. Furthermore, the Sca-1+ cells were markedly increased in the tunica media on the third day of vessel injury, SDF-1α expressions were obviously increased, and SDF-1α levels and Sca-1+ cells were almost synchronously increased within the neointima on the seventh day of vessel injury. These effects could effectually be reversed by knockdown of S100B by shRNA, RAGE inhibitor (SPF-ZM1), or CXCR4 blocker (AMD3100), indicating that migration of Sca-1+ cells from the adventitia into the neointima was associated with S100B/RAGE and SDF-1α/CXCR4. More importantly, the intermediate state of double-positive Sca-1+ and α-SMA cells was first found in the neointima of injured arteries, which could be substantially abrogated by using shRNA for S100B or blockade of CXCR4. S100B dose-dependently regulated SDF-1α expressions in VSMCs by activating PI3K/AKT and NF-κB, which were markedly abolished by PI3K/AKT inhibitor wortmannin and enhanced by p65 blocker PDTC. Furthermore, S100B was involved in human umbilical cord-derived Sca-1+ progenitor cells’ differentiation into VSMCs, especially in maintaining the intermediate state of double-positive Sca-1+ and α-SMA. Conclusions S100B triggered neointimal formation in rat injured arteries by maintaining the intermediate state of double-positive Sca-1+ progenitor and VSMCs, which were associated with direct activation of RAGE by S100B and indirect induction of SDF-1α by activating PI3K/AKT and NF-κB.

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 Mangiferin Inhibits PDGF-BB-Induced Proliferation and Migration of Rat Vascular Smooth Muscle Cells and Alleviates Neointimal Formation in Mice through the AMPK/Drp1 Axis

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Qi Wu ◽  
Yuanyang Chen ◽  
Zhiwei Wang ◽  
Xin Cai ◽  
Yanjia Che ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Neointimal Hyperplasia ◽  
Muscle Cells ◽  
Neointimal Formation ◽  
Artery Ligation ◽  
And Migration ◽  
Proliferation And Migration

Mangiferin is a naturally occurring xanthone C-glycoside that is widely found in various plants. Previous studies have reported that mangiferin inhibits tumor cell proliferation and migration. Excessive proliferation and migration of vascular smooth muscle cells (SMCs) is associated with neointimal hyperplasia in coronary arteries. However, the role and mechanism of mangiferin action in neointimal hyperplasia is still unknown. In this study, a mouse carotid artery ligation model was established, and primary rat smooth muscle cells were isolated and used for mechanistic assays. We found that mangiferin alleviated neointimal hyperplasia, inhibited proliferation and migration of SMCs, and promoted platelets derive growth factors-BB- (PDGF-BB-) induced contractile phenotype in SMCs. Moreover, mangiferin attenuated neointimal formation by inhibiting mitochondrial fission through the AMPK/Drp1 signaling pathway. These findings suggest that mangiferin has the potential to maintain vascular homeostasis and inhibit neointimal hyperplasia.

scholarly journals Cortistatin Inhibits Migration and Proliferation of Human Vascular Smooth Muscle Cells and Decreases Neointimal Formation on Carotid Artery Ligation

2013 ◽  
Vol 112 (11) ◽  
pp. 1444-1455 ◽  
Author(s):  
Mario Duran-Prado ◽  
Maria Morell ◽  
Virginia Delgado-Maroto ◽  
Justo P. Castaño ◽  
Jose Aneiros-Fernandez ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Carotid Artery ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Neointimal Formation ◽  
Artery Ligation ◽  
Carotid Artery Ligation
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