Autophagy Regulates Vascular Endothelial Cell eNOS and ET-1 Expression Induced by Laminar Shear Stress in an Ex Vivo Perfused System

Guo, Feng; Li, Xiaohong; Peng, Juan; Tang, Yaling; Yang, Qin; Liu, Lu‐Shan; Zuo, Wenqi; Jiang, Zhisheng; Xiao, Ming; Ni, Chu-Yu; Chen, Ruixing; Wei, Dangheng; Wang, Guixue

doi:10.1007/s10439-014-1033-5

Cited by 100 publications

(68 citation statements)

References 32 publications

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“…In contrast, pretreatment of rapamycin enhanced the expression of eNOS under laminar shear stress. 38 Acute treatment of a mouse model of Alzheimer's disease with rapamycin activated eNOS and NO production in the brain endothelium and preserved vascular density. 39 The apparent discrepancy suggests that rapamycin may initiate a different response under different conditions.…”

Section: Discussionmentioning

confidence: 99%

Curcumin Attenuates Rapamycin-induced Cell Injury of Vascular Endothelial Cells

Guo

Chen

Zhou

et al. 2015

Journal of Cardiovascular Pharmacology

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Although drug-eluting stents (DES) effectively improve the clinical efficacy of percutaneous coronary intervention, a high risk of late stent thrombosis and in-stent restenosis also exists after DES implantation. Anti-smooth muscle proliferation drugs, such as rapamycin, coating stents, not only inhibit the growth of vascular smooth muscle cells but also inhibit vascular endothelial cells and delay the reendothelialization. Therefore, the development of an ideal agent that protects vascular endothelial cells from rapamycin-eluting stents is of great importance for the next generation of DES. In this study, we demonstrated that rapamycin significantly inhibited the growth of rat aortic endothelial cells in both dose- and time-dependent manner in vitro. Cell apoptosis was increased and migration was decreased by rapamycin treatments in rat aortic endothelial cells in vitro. Surprisingly, treatment with curcumin, an active ingredient of turmeric, significantly reversed these detrimental effects of rapamycin. Moreover, curcumin increased the expression of vascular nitric oxide synthases (eNOS), which was decreased by rapamycin. Furthermore, caveolin-1, the inhibitor of eNOS, was decreased by curcumin. Knockdown of eNOS by small interfering RNA significantly abrogated the protective effects of curcumin. Taken together, our results suggest that curcumin antagonizes the detrimental effect of rapamycin on aortic endothelial cells in vitro through upregulating eNOS. Therefore, curcumin is a promising combined agent for the rescue of DES-induced reendothelialization delay.

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Section: Discussionmentioning

confidence: 99%

Curcumin Attenuates Rapamycin-induced Cell Injury of Vascular Endothelial Cells

Guo

Chen

Zhou

et al. 2015

Journal of Cardiovascular Pharmacology

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“…When pretreated with 3-methyladenine, endothelial NO synthase expression in ECs is inhibited and endothelin-1 expression is restored. 40 Overall, we may conclude that autophagy is a key cellular process in ECs that preserves endothelial function and prevents cardiovascular disease.…”

Section: Autophagy Preserves Endothelial Functionmentioning

confidence: 91%

Autophagy in Vascular Disease

Meyer

Grootaert

Michiels

et al. 2015

Circulation Research

254

179

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A utophagy is a complex intracellular process that delivers cytoplasmic constituents for degradation into lysosomes.1,2 Three main types of autophagy have been described: (1) microautophagy, comprising direct engulfment of cytoplasmic material by lysosomes via inward invaginations of the lysosomal membrane, (2) macroautophagy, characterized by formation of double-membrane sequestering compartments termed autophagosomes that fuse with lysosomes for delivery of cytoplasmic cargo, and (3) chaperone-mediated autophagy, mediated by a chaperone complex and lysosomal-associated membrane protein type 2A to degrade cytosolic proteins with a specific targeting motif. The term autophagy usually refers to macroautophagy, which is the most prevalent and beststudied form of autophagy. Also in this review, we will focus exclusively on macroautophagy, further cited as autophagy.Autophagy occurs at basal levels in most tissues to allow constitutive turnover of cytosolic components but is stimulated by environmental stress-related signals (eg, nutrient deprivation and oxidative injury) to recycle nutrients and to generate energy for maintenance of cell viability in unfavorable conditions.1 In addition to cellular stress, basal autophagy can be intensified by specific drugs, 3 indicating that the autophagic machinery is a potential therapeutic target for diverse diseases. Indeed, given that autophagy is involved in the prevention

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“…It was recently reported that autophagy is activated when cultured ECs or isolated rabbit carotid arteries were exposed to SS compared to static conditions. 43 Interestingly, pretreatment with the autophagy inducer rapamycin followed by SS enhanced the shear-induced eNOS expression suggesting that autophagy may potentiate the beneficial effects of SS on the endothelium. 43 However, in the context of RP, the role of autophagy in EC survival and, in particular, the effect of shear stress on autophagy are unknown.…”

Section: Autophagy and Mitophagy - Regulation By Rosmentioning

confidence: 99%

Fluid Mechanical Forces and Endothelial Mitochondria: A Bioengineering Perspective

et al. 2014

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Endothelial cell dysfunction is the hallmark of every cardiovascular disease/condition, including atherosclerosis and ischemia/reperfusion injury. Fluid shear stress acting on the vascular endothelium is known to regulate cell homeostasis. Altered hemodynamics is thought to play a causative role in endothelial dysfunction. The dysfunction is associated with/preceded by mitochondrial oxidative stress. Studies by our group and others have shown that the form and/or function of the mitochondrial network are affected when endothelial cells are exposed to shear stress in the absence or presence of additional physicochemical stimuli. The present review will summarize the current knowledge on the interconnections among intracellular Ca2+ - nitric oxide - mitochondrial reactive oxygen species, mitochondrial fusion/fission, autophagy/mitophagy, and cell apoptosis vs. survival. More specifically, it will list the evidence on potential regulation of the above intracellular species and processes by the fluid shear stress acting on the endothelium under either physiological flow conditions or during reperfusion (following a period of ischemia). Understanding how the local hemodynamics affects mitochondrial physiology and the cell redox state may lead to development of novel therapeutic strategies for prevention or treatment of the endothelial dysfunction and, hence, of cardiovascular disease.

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Autophagy Regulates Vascular Endothelial Cell eNOS and ET-1 Expression Induced by Laminar Shear Stress in an Ex Vivo Perfused System

Cited by 100 publications

References 32 publications

Curcumin Attenuates Rapamycin-induced Cell Injury of Vascular Endothelial Cells

Curcumin Attenuates Rapamycin-induced Cell Injury of Vascular Endothelial Cells

Autophagy in Vascular Disease

Fluid Mechanical Forces and Endothelial Mitochondria: A Bioengineering Perspective

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