Implications of autophagy for vascular smooth muscle cell function and plasticity

Salabei, Joshua K.; Hill, Bradford G.

doi:10.1016/j.freeradbiomed.2013.08.003

Cited by 87 publications

(64 citation statements)

References 173 publications

(193 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6). In accord, previous studies have shown that autophagy is involved in the function and plasticity of VSMCs [34,35]. Interestingly, everolimus has not demonstrated significant effects on the expression of ATG5, indicating that everolimus may induce autophagy of VSMCs in an ATG5-independent way.…”

Section: Discussionsupporting

confidence: 81%

Enhanced Autophagy by Everolimus Contributes to the Antirestenotic Mechanisms in Vascular Smooth Muscle Cells

Tang

Dong²,

Wei³

et al. 2014

J Vasc Res

View full text Add to dashboard Cite

Objective: The present study aims to investigate the underlying mechanisms accounting for the activities of everolimus to inhibit the growth of vascular smooth muscle cells (VSMCs), which contributes to restenosis. Methods: Primary VSMCs were cultured in media containing smooth muscle growth supplements and incubated with testing agents. Cell proliferation, cell cycle distribution, apoptosis and autophagy, and the key molecules involved, were examined. Results: Everolimus inhibited the proliferation of VSMCs by inhibiting the activation of ribosomal protein S6 kinase and phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1, and downregulating proliferating cellular nuclear antigen. Everolimus induced cell cycle arrest at the G₁ phase by downregulating cyclin D1 and upregulating p27, and increased apoptosis by downregulating Bcl-2, upregulating Bad and activating capsase-3 and poly ADP ribose polymerase. Everolimus enhanced autophagy by increasing the conversion of microtubule-associated protein 1 light chain 3 (LC3)-I to LC3-II, and upregulating Beclin 1. Specific autophagy inhibitors, 3-methyladenine and bafilomycin A1, significantly attenuated the inhibition of cell proliferation, the increased apoptosis and the altered expression of the above key proteins induced by everolimus. Conclusions: Enhanced autophagy by everolimus contributes to its antirestenotic activity and its abilities to inhibit cell proliferation and to induce apoptosis of VSMCs.

show abstract

Section: Discussionsupporting

confidence: 81%

Enhanced Autophagy by Everolimus Contributes to the Antirestenotic Mechanisms in Vascular Smooth Muscle Cells

Tang

Dong²,

Wei³

et al. 2014

J Vasc Res

View full text Add to dashboard Cite

show abstract

“…30 Further, studies on human primary aortic SMCs revealed that exposure of SMCs to oxidized LDL induced not only the expression of autophagy markers but also the expression of phagocytic markers. 31 SMCs transition from a contractile to a migratory and synthetic phenotype, reflected by a typical loss of SMCs markers, such as SMC-α-actin, myosin SMC heavy chains, and vimentin, has been reported in later stages of atherosclerosis 32 and could be supported by the negative correlation between ATG16L1 and SMC-α-actin staining observed here. When considering this negative correlation with the fact that lipid-phagocytosing α-actin-positive SMC which are gaining CD68-positivity, that is, converted to macrophage foam cells, will retain their α-actin positivity, 30 we can infer that our finding of a positive correlation between the areas of ATG16L1-positivity and the areas of Oil Red O positivity (neutral lipid content) and CD68-positive macrophages reflects rather the presence of ATG16L1 in monocytederived macrophages than in SMC-derived macrophages.…”

Section: Discussionsupporting

confidence: 84%

ATG16L1 Expression in Carotid Atherosclerotic Plaques Is Associated With Plaque Vulnerability

Magné

Gustafsson

Jin

et al. 2015

ATVB

View full text Add to dashboard Cite

Objective— Autophagy has emerged as a cell survival mechanism critical for cellular homeostasis, which may play a protective role in atherosclerosis. ATG16L1, a protein essential for early stages of autophagy, has been implicated in the pathogenesis of Crohn’s disease. However, it is unknown whether ATG16L1 is involved in atherosclerosis. Our aim was to analyze ATG16L1 expression in carotid atherosclerotic plaques in relation to markers of plaque vulnerability. Approach and Results— Histological analysis of 143 endarterectomized human carotid atherosclerotic plaques revealed that ATG16L1 was expressed in areas surrounding the necrotic core and the shoulder regions. Double immunofluorescence labeling revealed that ATG16L1 was abundantly expressed in phagocytic cells (CD68), endothelial cells (CD31), and mast cells (tryptase) in human advanced plaques. ATG16L1 immunogold labeling was predominantly observed in endothelial cells and foamy smooth muscle cells of the plaques. ATG16L1 protein expression correlated with plaque content of proinflammatory cytokines and matrix metalloproteinases. Analysis of Atg16L1 at 2 distinct stages of the atherothrombotic process in a murine model of plaque vulnerability by incomplete ligation and cuff placement in carotid arteries of apolipoprotein-E-deficient mice revealed a strong colocalization of Atg16L1 and smooth muscle cells only in early atherosclerotic lesions. An increase in ATG16L1 expression and autophagy flux was observed during foam cell formation in human macrophages using oxidized-LDL. Conclusions— Taken together, this study shows that ATG16L1 protein expression is associated with foam cell formation and inflamed plaque phenotype and could contribute to the development of plaque vulnerability at earlier stages of the atherogenic process.

show abstract

“…consistent with autophagosomes were reported in VSMCs within atherosclerotic lesions (16) and atheromas (17) in humans and animal models. Subsequent studies in animal models of cardiovascular disease, using transgenic animals overexpressing labeled autophagic proteins (e.g., GFP-LC3) to monitor autophagic activity, similarly reported evidence of autophagy in VSMCs (18).…”

Section: Autophagic Activity In All Cardiovascular Cell Typesmentioning

confidence: 94%

Autophagy in cardiovascular biology

Lavandero

Chiong

Rothermel³

et al. 2015

J. Clin. Invest.

280

211

View full text Add to dashboard Cite

Autophagy in the vascular systemEndothelial cells. Autophagy can be regulated in vascular endothelial cells by compounds circulating in the bloodstream or localized within the subendothelial layer of atherosclerotic plaque. For example, in cultured HUVECs, vitamin D increases beclin 1, a key comCardiovascular disease is the leading cause of death worldwide. As such, there is great interest in identifying novel mechanisms that govern the cardiovascular response to disease-related stress. First described in failing hearts, autophagy within the cardiovascular system has been widely characterized in cardiomyocytes, cardiac fibroblasts, endothelial cells, vascular smooth muscle cells, and macrophages. In all cases, a window of optimal autophagic activity appears to be critical to the maintenance of cardiovascular homeostasis and function; excessive or insufficient levels of autophagic flux can each contribute to heart disease pathogenesis. In this Review, we discuss the potential for targeting autophagy therapeutically and our vision for where this exciting biology may lead in the future.

show abstract

Implications of autophagy for vascular smooth muscle cell function and plasticity

Cited by 87 publications

References 173 publications

Enhanced Autophagy by Everolimus Contributes to the Antirestenotic Mechanisms in Vascular Smooth Muscle Cells

Enhanced Autophagy by Everolimus Contributes to the Antirestenotic Mechanisms in Vascular Smooth Muscle Cells

ATG16L1 Expression in Carotid Atherosclerotic Plaques Is Associated With Plaque Vulnerability

Autophagy in cardiovascular biology

Contact Info

Product

Resources

About