Osteopontin regulates α-smooth muscle actin and calponin in vascular smooth muscle cells

2011 ◽  
Vol 36 (2) ◽  
pp. 155-161 ◽  
Author(s):  
Hong Gao ◽  
Marlene C. Steffen ◽  
Kenneth S. Ramos
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Smooth Muscle Actin ◽  
Muscle Cells ◽  
Muscle Actin

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 Resveratrol Inhibits Phenotype Modulation by Platelet Derived Growth Factor-bb in Rat Aortic Smooth Muscle Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Mi Hee Lee ◽  
Byeong-Ju Kwon ◽  
Hyok Jin Seo ◽  
Kyeong Eun Yoo ◽  
Min Sung Kim ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Smooth Muscle Actin ◽  
Muscle Cells ◽  
Platelet Derived Growth Factor ◽  
Pathway Activation ◽  
Dependent Inhibition

Dedifferentiated vascular smooth muscle cells (VSMCs) are phenotypically modulated from the contractile state to the active synthetic state in the vessel wall. In this study, we investigated the effects of resveratrol on phenotype modulation by dedifferentiation and the intracellular signal transduction pathways of platelet derived growth factor-bb (PDGF-bb) in rat aortic vascular smooth muscle cells (RAOSMCs). Treatment of RAOSMCs with resveratrol showed dose-dependent inhibition of PDGF-bb-stimulated proliferation. Resveratrol treatment inhibited this phenotype change and disassembly of actin filaments and maintained the expression of contractile phenotype-related proteins such as calponin and smooth muscle actin-alpha in comparison with only PDGF-bb stimulated RAOSMC. Although PDGF stimulation elicited strong and detectable Akt and mTOR phosphorylations lasting for several hours, Akt activation was much weaker when PDGF was used with resveratrol. In contrast, resveratrol only slightly inhibited phosphorylations of 42/44 MAPK and p38 MAPK. In conclusion, RAOSMC dedifferentiation, phenotype, and proliferation rate were inhibited by resveratrol via interruption of the balance of Akt, 42/44MAPK, and p38MAPK pathway activation stimulated by PDGF-bb.

scholarly journals ALindera obtusilobaExtract Blocks Calcium-/Phosphate-Induced Transdifferentiation and Calcification of Vascular Smooth Muscle Cells and Interferes with Matrix Metalloproteinase-2 and Metalloproteinase-9 and NF-κB

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Christian Freise ◽  
Ki Young Kim ◽  
Uwe Querfeld
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Protein ◽  
Smooth Muscle Actin ◽  
Muscle Cells ◽  
Matrix Metalloproteinase 2 ◽  
Antitumor Effects ◽  
Vascular Calcifications

Vascular calcifications bear the risk for cardiovascular complications and have a high prevalence among patients with chronic kidney disease. Central mediators of vascular calcifications are vascular smooth muscle cells (VSMC). They transdifferentiate into a synthetic/osteoblast-like phenotype, which is induced, for example, by elevated levels of calcium and phosphate (Ca/P) due to a disturbed mineral balance. An aqueous extract fromLindera obtusiloba(LOE) is known to exert antifibrotic and antitumor effects or to interfere with the differentiation of preadipocytes. Using murine and rat VSMC cell lines, we here investigated whether LOE also protects VSMC from Ca/P-induced calcification. Indeed, LOE effectively blocked Ca/P-induced calcification of VSMC as shown by decreased VSMC mineralization and secretion of alkaline phosphatase. In parallel, mRNA expression of the calcification markers osterix and osteocalcin was reduced. Vice versa, the Ca/P-induced loss of the VSMC differentiation markers alpha smooth muscle actin and smooth muscle protein 22-alpha was rescued by LOE. Further, LOE blocked Ca/P-induced mRNA expressions and secretions of matrix metalloproteinases-2/-9 and activation of NF-κB, which are known contributors to vascular calcification. In conclusion, LOE interferes with the Ca/P-induced transdifferentiation/calcification of VSMC. Thus, LOE should be further analysed regarding a potential complementary treatment option for cardiovascular diseases including vascular calcifications.

Proliferation of vascular smooth muscle cells in glioblastoma multiforme

2010 ◽  
Vol 113 (2) ◽  
pp. 218-224 ◽  
Author(s):  
Hiroaki Takeuchi ◽  
Norichika Hashimoto ◽  
Ryuhei Kitai ◽  
Toshihiko Kubota ◽  
Ken-ichiro Kikuta
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Tumor Cells ◽  
Vascular Smooth Muscle Cells ◽  
Smooth Muscle Actin ◽  
Muscle Cells ◽  
Angiogenic Factors ◽  
Immunohistochemical Method ◽  
Vegf Expression

Object Glioblastomas multiforme (GBM) contain a higher number of α-smooth muscle actin (SMA)–positive vascular smooth muscle cells (VSMCs) than those in the respective normal neuronal tissue. The role of VSMCs during angiogenesis is unclear, and it is also uncertain whether and to what extent angiogenic factors might be involved in GBM VSMCs. In GBMs, the contribution of VSMCs in angiogenesis accompanying endothelial proliferation and the correlation of VSMC proliferation with vascular endothelial growth factor (VEGF) expression were examined using an immunohistochemical method. Methods The examined material, including surrounding brain tissue, came from 12 cases (6 men and 6 women) with classic GBM. Microvessel densities (MVDs) of CD31-immunoreactive vessels (CD31-MVD) and SMA-immunoreactive vessels (SMA-MVD) were obtained in areas selected from white matter, boundary, tumor (concentrated area of tumor cells), and perinecrosis. Subsequently, the SMA-MVD/CD31-MVD (SMA/CD31) rate, representing the percentage of vessels with VSMCs in the region, was calculated in each area. The VEGF immunoreactivity of tumor cells was examined, and cases were divided into 2 groups: < 30% VEGF expression of tumor cells (low VEGF group) and > 30% VEGF expression of tumor cells (high VEGF group). Results The SMA/CD31 rate of the boundary was significantly lower than that of the tumor (p < 0.005) and perinecrosis (p < 0.001). The SMA/CD31 rate of the high VEGF group was significantly higher than that of the low VEGF group (p < 0.05) in the tumor. Conclusions In GBMs, the transformation and proliferation of VSMCs may accompany neovascularization and may also be induced by angiogenic factors.

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