Smooth Muscle Cell Plasticity

Nguyen, Anh; Gomez, Delphine; Bell, Robert D.; Campbell, Julie H.; Clowes, Alexander W.; Gabbiani, Giulio; Giachelli, Cecilia M.; Parmacek, Michael S.; Raines, Elaine W.; Rusch, Nancy J.; Speer, Mei Y.; Sturek, Michael; Thyberg, Johan; Towler, Dwight A.; Weiser‐Evans, Mary C.M.; Yan, Chen; Miano, Joseph M.; Owens, Gary K.

doi:10.1161/circresaha.112.281048

Cited by 142 publications

(137 citation statements)

References 37 publications

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“…70,73 Over the years, however, several additional or alternative origins of plaque SMCs have been reported, including circulating progenitor cells, subpopulations of synthetic-type SMCs in the arterial media, or multipotent stem cells in the media or adventitia. 74,75 Some of these findings have subsequently been refuted or contested, 71,76 but exhaustive tracking of the origin of human lesional SMCs has yet to be performed. 70 Calcifications are common in progressive atherosclerotic lesions and increase with age.…”

Section: Fibrosis and Calcificationmentioning

confidence: 99%

Mechanisms of Plaque Formation and Rupture

Bentzon

Otsuka

Virmani

et al. 2014

Circulation Research

1,627

1,160

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Atherosclerosis causes clinical disease through luminal narrowing or by precipitating thrombi that obstructblood flow to the heart (coronary heart disease), brain (ischemic stroke), or lower extremities (peripheral vascular disease). The most common of these manifestations is coronary heart disease, including stable angina pectoris and the acute coronary syndromes. Atherosclerosis is a lipoprotein-driven disease that leads to plaque formation at specific sites of the arterial tree through intimal inflammation, necrosis, fibrosis, and calcification. After decades of indolent progression, such plaques may suddenly cause life-threatening coronary thrombosis presenting as an acute coronary syndrome. Most often, the culprit morphology is plaque rupture with exposure of highly thrombogenic, red cell-rich necrotic core material. The permissive structural requirement for this to occur is an extremely thin fibrous cap, and thus, ruptures occur mainly among lesions defined as thin-cap fibroatheromas. Also common are thrombi forming on lesions without rupture (plaque erosion), most often on pathological intimal thickening or fibroatheromas. However, the mechanisms involved in plaque erosion remain largely unknown, although coronary spasm is suspected. The calcified nodule has been suggested as a rare cause of coronary thrombosis in highly calcified and tortious arteries in older individuals. To characterize the severity and prognosis of plaques, several terms are used. Plaque burden denotes the extent of disease, whereas plaque activity is an ambiguous term, which may refer to one of several processes that characterize progression. Plaque vulnerability describes the short-term risk of precipitating symptomatic thrombosis. In this review, we discuss mechanisms of atherosclerotic plaque initiation and progression; how plaques suddenly precipitate life-threatening thrombi; and the concepts of plaque burden, activity, and vulnerability. (Circ Res.

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Section: Fibrosis and Calcificationmentioning

confidence: 99%

Mechanisms of Plaque Formation and Rupture

Bentzon

Otsuka

Virmani

et al. 2014

Circulation Research

1,627

1,160

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“…However, this concept is mainly based on in vitro results with cultured SMCs and conclusive in vivo studies that have assessed the contribution of SMC plasticity to the development of cells with alternative phenotypes within atherosclerotic plaques are lacking. 5,8 Two previous studies found by immunostaining of human plaque sections that some intimal cells coexpressed markers of SMCs and macrophages, suggesting the existence of a SMC-macrophage chimeric cell type in human lesions. 10,11 However, these experiments did not allow one to determine the origin of the chimeric cells (ie, whether they originated from SMCs, macrophages, or other cell types).…”

mentioning

confidence: 95%

“…[4][5][6][7] One unsolved issue is the role of mature smooth muscle cells (SMCs) that reside in the vascular media. 8,9 It is generally accepted that vascular SMCs are not terminally differentiated and can undergo phenotypic transitions during lesion development. However, this concept is mainly based on in vitro results with cultured SMCs and conclusive in vivo studies that have assessed the contribution of SMC plasticity to the development of cells with alternative phenotypes within atherosclerotic plaques are lacking.…”

mentioning

confidence: 99%

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Transdifferentiation of Vascular Smooth Muscle Cells to Macrophage-Like Cells During Atherogenesis

Feil

Fehrenbacher

Łukowski

et al. 2014

Circulation Research

417

364

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“…After vascular injury, normally contractile SMCs dedifferentiated to a state of proliferation, migration, and extracellular matrix secretion, a process referred to as phenotypic change. A key feature of this process is the loss of expression of SMC‐specific gene products, such as α‐SMA 34, 35. We found that BW723C86 further decreased α‐SMA expression in wire‐injured arteries compared with the vehicle group at 3 days after injury (Figure 2A).…”

Section: Resultsmentioning

confidence: 85%

Inhibition of 5‐Hydroxytryptamine Receptor 2B Reduced Vascular Restenosis and Mitigated the β‐Arrestin2–Mammalian Target of Rapamycin/p70S6K Pathway

Liu

Wang

et al. 2018

JAHA

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BackgroundAs a monoamine neurotransmitter, 5‐hydroxytryptamine (5‐HT) or serotonin modulates mood, appetite, and sleep. Besides, 5‐HT also has important peripheral functions. 5‐HT receptor 2B (5‐HT2BR) plays a key role in cardiovascular diseases, such as pulmonary arterial hypertension and cardiac valve disease. Percutaneous intervention has been used to restore blood flow in occlusive vascular disease. However, restenosis remains a significant problem. Herein, we investigated the role of 5‐HT2BR in neointimal hyperplasia, a key pathological process in restenosis.Methods and ResultsThe expression of 5‐HT2BR was upregulated in wire‐injured mouse femoral arteries. In addition, BW723C86, a selective 5‐HT2BR agonist, promoted the injury response during restenosis. 5‐HT and BW723C86 stimulated migration and proliferation of rat aortic smooth muscle cells. Conversely, LY272015, a selective antagonist, attenuated the 5‐HT–induced smooth muscle cell migration and proliferation. In vitro study showed that the promigratory effects of 5‐HT2BR were mediated through the activation of mammalian target of rapamycin (mTOR)/p70S6K signaling in a β‐arrestin2–dependent manner. Inhibition of mammalian target of rapamycin or p70S6K mitigated 5‐HT2BR–mediated smooth muscle cell migration. Mice with deficiency of 5‐HT2BR showed significantly reduced neointimal formation in wire‐injured arteries.ConclusionsThese results demonstrated that activation of 5‐HT2BR and β‐arrestin2–biased downstream signaling are key pathological processes in neointimal formation, and 5‐HT2BR may be a potential target for the therapeutic intervention of vascular restenosis.

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Smooth Muscle Cell Plasticity

Cited by 142 publications

References 37 publications

Mechanisms of Plaque Formation and Rupture

Mechanisms of Plaque Formation and Rupture

Transdifferentiation of Vascular Smooth Muscle Cells to Macrophage-Like Cells During Atherogenesis

Inhibition of 5‐Hydroxytryptamine Receptor 2B Reduced Vascular Restenosis and Mitigated the β‐Arrestin2–Mammalian Target of Rapamycin/p70S6K Pathway

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