The Mechanism Underlying Vascular Smooth Muscle Cell Apoptosis Induced by Atorvastatin may be Mainly Associated with Down-regulation of Survivin Expression

Xu, Yiguan; Zhou, Shenghua; Li, Yuguang; Zheng, Chunhua; Li, Xuping; Liu, Qiming; Xu, Duanmin; Shang, Chao

doi:10.1007/s10557-007-6018-2

Cited by 11 publications

(11 citation statements)

References 34 publications

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“…Similar to the result by Simosa et al (2005) that delivery of survivin mutants (AdT34A) after balloon injury attenuated neointimal hyperplasia, Daniel et al (2012) revealed that survivin played a crucial role in inhibiting the proliferative response of VSMCs and neointima formation mediated by a highly potent inhibitor of transcription-3. In addition, our previous in vitro experiment found that VSMCs apoptosis induced by atorvastatin may be mainly associated with down-regulation of survivin expression (Xu et al, 2007). In line with the above investigations, the present in vivo study identified that the inhibition of neointimal proliferation by atorvastatin may closely be related to VSMCs apoptosis and down-regulation of survivin levels after vascular injury.…”

Section: Discussionsupporting

confidence: 89%

Inhibition of neointimal hyperplasia in rats treated with atorvastatin after carotid artery injury may be mainly associated with down-regulation of survivin and Fas expression

Zhou

Fang

et al. 2014

Pharmaceutical Biology

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(2014) Inhibition of neointimal hyperplasia in rats treated with atorvastatin after carotid artery injury may be mainly associated with down-regulation of survivin and Fas expression, Pharmaceutical Biology, 52:9, 1196-1203, DOI: 10.3109/13880209.2014 . The plasma levels of survivin and sFas were gradually increased with the neointimal hyperplasia and increasingly decreased after atorvastatin treatment. The plasma levels of survivin and sFas in rats were elevated at 3 d (464.80 ± 105.27 pg/ml and 3256.00 ± 478.20 pg/ml, respectively), reached the peak of survivin at 14 d (1089.20 ± 232.32 pg/ml) and sFas at 7 d (4362.00 ± 639.92 pg/ml) and decreased at 28 d (562.00 ± 90.11 pg/ml and 2148.00 ± 257.14 pg/ml, respectively) in the model group. Compared with the model group, the atorvastatin treatment group has significantly less neointimal hyperplasia and more apoptosis of VSMCs. Conclusions: Atorvastatin can inhibit neointimal hyperplasia and promote SMCs apoptosis in neointimal layers, which may be mainly associated with down-regulation of survivin and Fas expression after CAI of rat.

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Section: Discussionsupporting

confidence: 89%

Inhibition of neointimal hyperplasia in rats treated with atorvastatin after carotid artery injury may be mainly associated with down-regulation of survivin and Fas expression

Zhou

Fang

et al. 2014

Pharmaceutical Biology

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“…However, agents currently in more widespread clinical use might also have a role. Thus HMG-Co-A reductase inhibitors (statins) have been reported to inhibit phosphate-induced apoptosis of smooth muscle cells [93], but the evidence is ambiguous [94,95] and simvastatin did not reverse established arterial calcification in one human study [96]. The potential benefit of peroxisome proliferatoractivated receptor (PPAR)γ agonists has yet to be fully explored, although their use is known to be associated with decreased expression of pro-inflammatory cytokines and they have also been reported to inhibit neovascularisation.…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

Medial arterial calcification in diabetes and its relationship to neuropathy

et al. 2009

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“…A second pathway involved in SMC apoptosis is represented by the p53/p21 WAF1/Cip1 proteins; however, the induction of apoptosis by statins seems to be independent of p53 [147]. Another possible mechanism of statin-induced apoptosis has been finally proposed by the group of Xu, who described the downregulation of the expression of the antiapoptotic protein survivin by atorvastatin [148].…”

Section: Effect Of Statins On Apoptosis Of Smooth Muscle Cellsmentioning

confidence: 99%

Inhibition of Smooth Muscle Cell Migration and Proliferation by Statins

Arnaboldi

Baetta

Ferri

et al. 2008

IEMAMC

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Vascular smooth muscle cell (SMC) migration and proliferation contribute to the pathobiology of atherosclerosis and of instent restenosis, transplant vasculopathy and vein by-pass graft failure. Since mevalonate (MVA) and other intermediates of cholesterol biosynthesis (isoprenoids) are necessary for cell migration and proliferation, inhibition of 3-methyl-3-glutaryl-coenzyme A (HMG-CoA) reductase, the rate limiting step of the MVA pathway, has the potential to result in antiatherosclerotic effects. Indeed statins, competitive inhibitors of the HMG-CoA reductase, have shown the capability to interfere with migration and proliferation of SMC in diverse experimental models. Here we summarize in vitro, in vivo, and ex vivo evidence of the inhibitory effects of statins on SMC proliferation and migration and discuss the molecular mechanisms involved in their pharmacodynamic action. Altogether, this evidence suggests direct vascular antiatherosclerotic properties of statins. However, it is important to mention that statins failed to prevent intimal thickening when studied in clinical setting characterized by accelerated vascular SMC proliferation and migration (e.g. restenosis after PTCA and instent restenosis), thus leaving open the question of the clinical relevance of these direct vascular effects of statins. ROLE OF SMOOTH MUSCLE CELL IN ATHEROGENESISWith the increasing knowledge on the pathogenesis of atherosclerosis, it appears that the prevention of cardiovascular disease will involve not only risk factor correction, but also direct pharmacological control of processes occurring in the arterial wall [1-3].Smooth muscle cells (SMC) represent the predominant population in the arterial medial layer and play a pivotal role in the maintenance of the functional and structural integrity of the artery, thanks to their contractility and synthesis of extracellular vascular matrix [4]. Together with platelets, monocytes and endothelial cells, SMC are also strongly involved in atherosclerotic lesion formation. SMC exist in two main phenotypes: synthetic and contractile [5]. The latter phenotype is characterized by a high expression of genes encoding for proteins involved in the maintenance of structure and function of myofilaments: cells in this situation are strongly differentiated, quiescent and respond to stimuli like vasoconstrictors and vasodilators as endothelins, catecholamines, prostacyclin, neuropeptides, leukotrienes and nitric oxide, while are silent towards mitogens [6]. On the other hand, when in synthetic phenotype, SMC increase the expression of genes encoding for growth factors, cytokines and their receptors, while reduce the expression of -actin [2]; these cells are immature, dedifferentiated but are able to accumulate lipids, becoming foam cells, to secrete both extracellular matrix and metalloproteinases, which degrade the matrix itself [2]. Functional differences are paralleled by morphological ones: SMC with contractile phenotype have a "spindle-like" shape and their cytoplasm is enriched in many myofil...

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The Mechanism Underlying Vascular Smooth Muscle Cell Apoptosis Induced by Atorvastatin may be Mainly Associated with Down-regulation of Survivin Expression

Cited by 11 publications

References 34 publications

Inhibition of neointimal hyperplasia in rats treated with atorvastatin after carotid artery injury may be mainly associated with down-regulation of survivin and Fas expression

Inhibition of neointimal hyperplasia in rats treated with atorvastatin after carotid artery injury may be mainly associated with down-regulation of survivin and Fas expression

Medial arterial calcification in diabetes and its relationship to neuropathy

Inhibition of Smooth Muscle Cell Migration and Proliferation by Statins

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