scholarly journals Adaptation of mitochondrial expression and ATP production in dedifferentiating vascular smooth muscle cells

2017 ◽  
Vol 95 (12) ◽  
pp. 1473-1479 ◽  
Author(s):  
Celena Scheede-Bergdahl ◽  
Andreas Bergdahl
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Mitochondrial Function ◽  
Complex I ◽  
Clinical Manifestations ◽  
Western World ◽  
Aortic Tissue ◽  
Atp Production

Atherosclerosis is one of the leading causes of morbidity and mortality in the Western world. Although the clinical manifestations of this disease are well documented, the etiology and progression remain to be fully understood. Recently, the mitochondria have been implicated in important cellular processes involved in development of atherosclerosis. Despite the link between mitochondria and atherosclerosis, early-phase mechanisms of the disease have yet to be elucidated. The aim of this project was to explore the role of mitochondria in vascular smooth muscle (VSMC) dedifferentiation. A murine in vitro model, involving organ culture of aortic tissue in serum-free media, was used. Mitochondrial function was measured by high-resolution respirometry. Proteins associated with the VSMC phenotype switch, as well as mitochondrial density, were assessed by immunoblotting. The findings show that intrinsic mitochondrial Complex I activity is significantly upregulated during VSMC dedifferentiation. Diminished coupling between phosphorylation and oxidation was also found, indicating a greater ADP:ATP ratio. This data suggests increased leak in the electron transport chain and altered mitochondrial function specifically at Complex I. This project provides important information regarding the role of mitochondria in the early atherosclerotic process and that detectable changes in mitochondrial function and expression are related to VSMC dedifferentiation.

Role of GADD153 (growth arrest- and DNA damage-inducible gene 153) in vascular smooth muscle cell apoptosis

2001 ◽  
Vol 100 (3) ◽  
pp. 275-281 ◽  
Author(s):  
Michiya IGASE ◽  
Takafumi OKURA ◽  
Michitsugu NAKAMURA ◽  
Yasunori TAKATA ◽  
Yutaka KITAMI ◽  
...  
Keyword(s):  
Dna Damage ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Molecular Mechanisms ◽  
Growth Arrest ◽  
Cell Contact ◽  
Inducible Gene

GADD153 (growth arrest- and DNA damage-inducible gene 153) is expressed at very low levels in growing cells, but is markedly induced in response to a variety of cellular stresses, including glucose deprivation, exposure to genotoxic agents and other growth-arresting situations. Forced expression of GADD153 induces cell cycle arrest in many types of cells. It is also reported that GADD153 is directly associated with apoptosis. Recently we have reported that platelet-derived growth factor (PDGF)-BB induces apoptosis in cultured vascular smooth muscle cells (VSMC), but only when 100% confluency is reached. These results suggested that cell–cell contact inhibition (cell growth arrest) may be a critical factor for induction of VSMC apoptosis by PDGF-BB. In the present study, we explored the role of GADD153, one of a number of growth-arrest-related gene products, in the molecular mechanisms of VSMC apoptosis in vitro and in vivo. GADD153 was markedly induced at both the mRNA and protein levels, in parallel with the induction of VSMC apoptosis, after treatment with PDGF-BB. Moreover, overexpression of GADD153 in VSMC significantly reduced cell viability and induced apoptosis. In the carotid artery balloon injury model in rats, GADD153 protein was expressed in apoptotic VSMC which were positively stained by in situ DNA labelling. These results demonstrate an important role for GADD153 in the molecular mechanisms of VSMC apoptosis.

scholarly journals Exosomal miR-151-3p Induces Calcium Deposition in Vascular Smooth Muscle Cells by Inhibiting Atg5

2021 ◽  
Author(s):  
Li Chen ◽  
Rongrong Zhang ◽  
Jinyin Li ◽  
Yiping Gao ◽  
Shilong Mao
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Calcium Deposition ◽  
Alizarin Red ◽  
Potential Biomarker

Abstract Background: Calcium deposition in vascular smooth muscle cells (VSMCs) can lead to the rigidity of the vasculature and an increase of risk in cardiac events. This study aimed to explore the role of exosomal microRNA-151-3p (miR-151-3p) in the regulation of VSMC calcification. Methods: A cellular calcification model was established using the mouse primary aortic VSMCs by β-glycerophosphate treatment. The calcium deposition was evaluated by Alizarin Red staining. The expression of miR-151-3p in exosomes was evaluated by qRT-PCR. The relationship between miR-151-3p and Atg5 was determined by bioinformatics analysis and dual-luciferase gene reporter assay. The exosome derived from mouse VSMCs transfected with miR-151-3p mimics/inhibitor were isolated and used to stimulate VSMCs. The expression of Atg5, α-SMA, OPN, Runx2 and BMP2 was evaluated by western blot. An animal model was established to investigate the role of miR-151-3p in exosomes.Results: MiR-151-3p was significantly upregulated in the exosomes of VSMCs treated with β-glycerophosphate. Exosomes derived from calcific VSMCs increased the calcium deposition of general VSMCs without any treatment. Exosomes derived from miR-151-3p mimics transfected VSMCs increased the expression of Runx2 and BMP2, while reduced the expression of α-SMA and OPN in general VSMCs. and exosomes derived from miR-151-3p inhibitor transfected VSMCs reversed these effects in vitro. Meanwhile, miR-151-3p served as a ceRNA of Atg5 by directly binding to the 3'UTR of Atg5. Moreover, the expression of α-SMA, OPN, Runx2 and BMP2 in vivo was consistent with the results in VSMCs in vitro.Conclusion: Our study revealed that miR-151-3p in VSMCs-derived exosomes might induce calcium deposition through regulating Atg5 expression, suggesting that miR-151-3p might be a potential biomarker for vascular calcification.

scholarly journals Endothelial-derived extracellular microRNA-92a promotes arterial stiffness by regulating phenotype changes of vascular smooth muscle cells

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Chen Wang ◽  
Haoyu Wu ◽  
Yuanming Xing ◽  
Yulan Ye ◽  
Fangzhou He ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Arterial Stiffness ◽  
Vascular Smooth Muscle ◽  
Vascular Endothelial Cells ◽  
Locked Nucleic Acid ◽  
Vascular Endothelial ◽  
Ang Ii

AbstractEndothelial dysfunction and vascular smooth muscle cell (VSMC) plasticity are critically involved in the pathogenesis of hypertension and arterial stiffness. MicroRNAs can mediate the cellular communication between vascular endothelial cells (ECs) and neighboring cells. Here, we investigated the role of endothelial-derived extracellular microRNA-92a (miR-92a) in promoting arterial stiffness by regulating EC–VSMC communication. Serum miR-92a level was higher in hypertensive patients than controls. Circulating miR-92a level was positively correlated with pulse wave velocity (PWV), systolic blood pressure (SBP), diastolic blood pressure (DBP), and serum endothelin-1 (ET-1) level, but inversely with serum nitric oxide (NO) level. In vitro, angiotensin II (Ang II)-increased miR-92a level in ECs mediated a contractile-to-synthetic phenotype change of co-cultured VSMCs. In Ang II-infused mice, locked nucleic acid-modified antisense miR-92a (LNA-miR-92a) ameliorated PWV, SBP, DBP, and impaired vasodilation induced by Ang II. LNA-miR-92a administration also reversed the increased levels of proliferative genes and decreased levels of contractile genes induced by Ang II in mouse aortas. Circulating serum miR-92a level and PWV were correlated in these mice. These findings indicate that EC miR-92a may be transported to VSMCs via extracellular vesicles to regulate phenotype changes of VSMCs, leading to arterial stiffness.

scholarly journals Regulation of PKC Autophosphorylation by Calponin in Contractile Vascular Smooth Muscle Tissue

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Hak Rim Kim ◽  
Cynthia Gallant ◽  
Kathleen G. Morgan
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Contraction ◽  
Smooth Muscle Tissue ◽  
Hydrophobic Site ◽  
Regulatory Phosphorylation ◽  
Motif Site ◽  
Key Enzyme

Protein kinase C (PKC) is a key enzyme involved in agonist-induced smooth muscle contraction. In some cases, regulatory phosphorylation of PKC is required for full activation of the enzyme. However, this issue has largely been ignored with respect to PKC-dependent regulation of contractile vascular smooth muscle (VSM) contractility. The first event in PKC regulation is a transphosphorylation by PDK at a conserved threonine in the activation loop of PKC, followed by the subsequent autophosphorylation at the turn motif and hydrophobic motif sites. In the present study, we determined whether phosphorylation of PKC is a regulated process in VSM and also investigated a potential role of calponin in the regulation of PKC. We found that calponin increases the level of in vitro PKCαphosphorylation at the PDK and hydrophobic sites, but not the turn motif site. In vascular tissues, phosphorylation of the PKC hydrophobic site, but not turn motif site, as well as phosphorylation of PDK at S241 increased in response to phenylephrine. Calponin knockdown inhibits autophosphorylation of cellular PKC in response to phenylephrine, confirming results with recombinant PKC. Thus these results show that autophosphorylation of PKC is regulated in dVSM and calponin is necessary for autophosphorylation of PKC in VSM.

scholarly journals The Potential Role of hsa_circ_0005505 in the Rupture of Human Intracranial Aneurysm

2021 ◽  
Vol 8 ◽  
Author(s):  
Xin Chen ◽  
Shuzhe Yang ◽  
Junhua Yang ◽  
Qingyuan Liu ◽  
Maogui Li ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Intracranial Aneurysm ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Intracranial Aneurysms ◽  
Circular Rna ◽  
Circular Rnas ◽  
Ruptured Intracranial Aneurysms

Objective: Recently, abundant number of studies have revealed many functions of circular RNAs in multiple diseases, however, the role of circular RNA in the rupture of human intracranial aneurysm is still unknown. This study aims to explore the potential functions of circular RNA in the rupture of human intracranial aneurysms.Methods: The differentially expressed circular RNAs between un-ruptured intracranial aneurysms (n = 5) and ruptured intracranial aneurysms (n = 5) were analyzed with the Arraystar human circRNAs microarray. Quantitative real-time PCR (qPCR) was used to verify the results of the circRNA microarray. The role of circular RNA in intracranial aneurysm rupture was assessed in vitro. MTT assay, CCK-8 assay, Caspase3/7 assay, assay of cell apoptosis and Celigo wound healing was conducted to evaluate the relationship between circular RNA and the rupture of human intracranial aneurysms.Results: A total of 13,175 circRNA genes were detected. Among them 63 circRNAs upregulated and 54 circRNAs downregulated significantly in ruptured intracranial aneurysms compared with un-ruptured intracranial aneurysms (p < 0.05 Fold Change > 1.5). Five upregulated circRNAs were selected for further study (hsa_circ_0001947, hsa_circ_0043001, hsa_circ_0064557, hsa_circ_0058514, hsa_circ_0005505). The results of qPCR showed only hsa_circ_0005505 significantly upregulated (p < 0.05). The expression of hsa_circ_0005505 was higher in ruptured intracranial aneurysm tissues. And our in vitro data showed that hsa_circRNA_005505 promotes the proliferation, migration and suppresses the apoptosis of vascular smooth muscle cell.Conclusion: This study revealed an important role of hsa_circ_0005505 in the proliferation, migration and apoptosis of vascular smooth muscle cell, and indicated that hsa_circ_0005505 may associate with the pathological process of intracranial aneurysms.

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