Mitochondrial metabolism and the control of vascular smooth muscle cell proliferation

Chiong, Mario; Cartes-Saavedra, Benjamín; Norambuena-Soto, Ignacio; Mondaca‐Ruff, David; Morales, Pablo E.; García-Miguel, Marina; Mellado, Rosemarie

doi:10.3389/fcell.2014.00072

Cited by 117 publications

(89 citation statements)

References 99 publications

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“…Studies have demonstrated that abnormal proliferation of vascular smooth muscle cells (VSMCs) play a critical role in the pathogenesis of cardiovascular diseases 456. However, to our best knowledge, the underlying molecular mechanisms thereof remain unclear.…”

Section: Introductionmentioning

confidence: 99%

miR-379 Inhibits Cell Proliferation, Invasion, and Migration of Vascular Smooth Muscle Cells by Targeting Insulin-Like Factor-1

Wang

Zhang

et al. 2017

Yonsei Med J

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PurposeMicroRNAs are small non-coding RNAs that play important roles in vascular smooth muscle cell (VSMC) function. This study investigated the role of miR-379 on proliferation, invasion, and migration of VSMCs and explored underlying mechanisms thereof.Materials and MethodsMicroRNA, mRNA, and protein levels were determined by quantitative real-time PCR and western blot. The proliferative, invasive, and migratory abilities of VSMCs were measured by CCK-8, invasion, and wound healing assay, respectively. Luciferase reporter assay was used to confirm the target of miR-379.ResultsPlatelet-derived growth factor-bb was found to promote cell proliferation and suppress miR-379 expression in VSMCs. Functional assays demonstrated that miR-379 inhibited cell proliferation, cell invasion, and migration. Flow cytometry results further showed that miR-379 induced apoptosis in VSMCs. TargetScan analysis and luciferase report assay confirmed that insulin-like growth factor-1 (IGF-1) 3'UTR is a direct target of miR-379, and mRNA and protein levels of miR-379 and IGF-1 were inversely correlated. Rescue experiments showed that enforced expression of IGF-1 sufficiently overcomes the inhibitory effect of miR-379 on cell proliferation, invasion, and migration in VSMCs.ConclusionOur results suggest that miR-379 plays an important role in regulating VSMCs proliferation, invasion, and migration by targeting IGF-1.

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Section: Introductionmentioning

confidence: 99%

miR-379 Inhibits Cell Proliferation, Invasion, and Migration of Vascular Smooth Muscle Cells by Targeting Insulin-Like Factor-1

Wang

Zhang

et al. 2017

Yonsei Med J

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“…by phenotype change switch over to its synthetic/ proliferative type and fibroblasts switch to 286 myofibroblasts which has features similar to VSMC (synthetic /proliferative ) phenotype but are 287 hyper contractile. In spirit of aerobic glycolysis / proliferation happening in these states i will call 288 these states as Warburg irreversible dedifferentiation states (68,77). But what triggers this cell phenotype change apart from the glycolysis shift?…”

Section: Warburg Common Pathogenesis Model In Sepsis (Figure 2): 173mentioning

confidence: 99%

“…VSMC proliferation / dedifferentiation have been 263 already related to various pathologies and this change has been related to Warburg effect (68). 264…”

Section: Warburg Common Pathogenesis Model In Sepsis (Figure 2): 173mentioning

confidence: 99%

Fundamental role of Warburg effect in various pathophysiological processes

Natesan¹

2017

Preprint

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Even though high NO via iNOS was involved in most of the pathologies including sepsis, any 56 substance that inhibits or uncouples the mitochondrial respiration can initiate this Warburg effect 57 and irreversible dedifferentiation. A mild and reversible Warburg differentiation dedifferentiation 58 effect may be necessary for normal functioning and the same effect in exaggerated and irreversible 59 way leading to irreversible dedifferentiation states may be the underlying mechanism in most of the 60 diseases including septic shock. 61 62 Keywords: Septic shock, Warburg effect, dedifferentiation, differentiation therapy, ascorbic acid, 63 adrenergic blockers, glycolysis. 64Abbreviations : systemic hypertension(SHT), pulmonary arterial hypertension (PAH),congestive 65 heart failure (CHF), acute kidney injury(AKI),acute respiratory distress syndrome(ARDS),diabetes 66 mellitus(DM),inducible nitric oxide synthase (iNOS) . 67 68 69 70 INTRODUCTION: 71This review article tries to show the fundamental role played by Warburg effect in most of the 72 pathologies. Warburg common pathogenesis model is proposed to show the common underlying 73 mechanism in most of the pathologies and septic shock was used as the base model. 74Sepsis is the harmful systemic response of the host to the infection (1). According to Lewis Thomas 75 the host's response to pathogen is more detrimental than the pathogen itself (2). Septic shock and 76 severe sepsis associated multi-organ dysfunction carries high mortality rate ~ 40 -70% (3,4). 77Septic shock is refractory to the vasopressors in most of the cases; this includes norepinephrine, the 78 primary drug used in reviving blood pressure in septic shock. Vascular hypo reactivity to various 79 vasopressors in septic shock has been studied extensively, many reviews are available (5,86). 80Irrespective of advances in this field, exact underlying mechanism behind septic shock is still a 81 mystery. Post mortem studies couldn't find the underlying cause in most of the cases, surprisingly 82 most of the organs looked normal (6).Lot of treatment options which were successful in animal 83 models were failed to show benefit in human studies, ranging from Nitric oxide Synthase (NOS) 84Inhibitors, Cyclooxygenase (COX) Inhibitors, endotoxin neutralizing proteins, TNF alpha 85 antagonists etc.., (3). Some of the recent promising directions include, counterintuitive use of 86 antihypertensive in septic shock -alpha2 adrenergic receptor agonists -clonidine (7-9), beta 87 blockers reviewed in (10, 11) -aimed to reduce the sympathetic hyper activation and hyper 88 metabolism associated with sepsis. Alpha2 AR antagonist also has been shown to improve survival 89 in sepsis animal model (12). Vitamin C has been used in sepsis reviewed in (13), Glycolysis 90 inhibitor shikonin (14), cytochrome C (15) and Caffeine (16). 91 Warburg common pathogenesis model has been proposed in this review article to explain the role of 92Warburg effect in most of the pathologies using septic shock as the base model. The model was 9...

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“…However, in response to vascular damage or inflammatory stimulations, VSMCs may undergo phenotypic changes to an uncontrolled proliferating and migratory state (1). It has been well established that the abnormal proliferation and migration of VSMCs in arterial walls is crucial in the development and progression of cardiovascular disorders, including intimal hyperplasia, arteriosclerosis and restenosis following percutaneous coronary intervention (PCI) (2,3).…”

Section: Introductionmentioning

confidence: 99%

Suppressive effect of formononetin on platelet-derived growth factor-BB-stimulated proliferation and migration of vascular smooth muscle cells

Chen

Liu

Cai

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) has been implicated in intimal hyperplasia, atherosclerosis and restenosis following percutaneous coronary intervention. Formononetin, a phytoestrogen extracted from the root of Astragalus membranaceus, has been widely used in Chinese tradition medicine due to its protective effects against certain symptoms of cancer, hypertension, inflammation, hypoxia-induced cytotoxicity and ovariectomy-induced bone loss. However, the effect of formononetin on platelet-derived growth factor (PDGF)-BB-induced proliferation and migration of VSMCs, as well as the underlying molecular mechanism, remains largely unclear. In the present study, treatment with formononetin significantly inhibited PDGF-BB-induced proliferation and migration of human VSMCs. Investigation into the underlying molecular mechanism revealed that the administration of formononetin suppressed PDGF-BB-stimulated switch of VSMCs to a proliferative phenotype. Furthermore, treatment with formononetin inhibited the PDGF-BB-induced upregulation of cell cycle-related proteins, matrix metalloproteinase (MMP2) and MMP9. In addition, the that administration of formononetin inhibited the phosphorylation of AKT induced by PDGF-BB in VSMCs. The present results suggest that formononetin has a suppressive effect on PDGF-BB-stimulated VSMCs proliferation and migration, which may occur partly via the inhibition of AKT signaling pathway. Therefore, formononetin may be useful for the treatment of intimal hyperplasia, atherosclerosis and restenosis.

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Mitochondrial metabolism and the control of vascular smooth muscle cell proliferation

Cited by 117 publications

References 99 publications

miR-379 Inhibits Cell Proliferation, Invasion, and Migration of Vascular Smooth Muscle Cells by Targeting Insulin-Like Factor-1

miR-379 Inhibits Cell Proliferation, Invasion, and Migration of Vascular Smooth Muscle Cells by Targeting Insulin-Like Factor-1

Fundamental role of Warburg effect in various pathophysiological processes

Suppressive effect of formononetin on platelet-derived growth factor-BB-stimulated proliferation and migration of vascular smooth muscle cells

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