Platelet-derived growth factor regulates vascular smooth muscle phenotype via mammalian target of rapamycin complex 1

Ha, Jung Min; Yun, Sung Ji; Kim, Young Whan; Jin, Seo Yeon; Lee, Hye Sun; Song, Sang Heon; Shin, Hwa Kyoung; Bae, Sun Sik

doi:10.1016/j.bbrc.2015.05.097

Cited by 47 publications

(44 citation statements)

References 23 publications

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“…They differ from other terminally differentiated cells such as cardiac and skeletal myocytes in that they maintain plasticity in modulating from a contractile to a synthetic phenotype in response to various stimuli 2,3 . In the normal vasculature environment, SMC maintain their contractile phenotype and show low proliferation and migration 4,5 .…”

Section: Introductionmentioning

confidence: 99%

Transdifferentiation of human endothelial progenitors into smooth muscle cells

Atchison

Chen

et al. 2016

Biomaterials

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Access to smooth muscle cells (SMC) would create opportunities for tissue engineering, drug testing, and disease modeling. Herein we report the direct conversion of human endothelial progenitor cells (EPC) to induced smooth muscle cells (iSMC) by induced expression of MYOCD. The EPC undergo a cytoskeletal rearrangement resembling that of mesenchymal cells within 3 days post initiation of MYOCD expression. By day 7, the reprogrammed cells show upregulation of smooth muscle markers ACTA2, MYH11, and TAGLN by qRT-PCR and ACTA2 and MYH11 expression by immunofluorescence. By two weeks, they resemble umbilical artery SMC in microarray gene expression analysis. The iSMC, in contrast to EPC control, show calcium transients in response to phenylephrine stimulation and a contractility an order of magnitude higher than that of EPC as determined by traction force microscopy. Tissue-engineered blood vessels constructed using iSMC show functionality with respect to flow- and drug-mediated vasodilation and vasoconstriction.

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Section: Introductionmentioning

confidence: 99%

Transdifferentiation of human endothelial progenitors into smooth muscle cells

Atchison

Chen

et al. 2016

Biomaterials

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“…Expression of PDGF‐BB (brown), a potent regulatory molecule of VSMC phenotypes,21, 22, 23, 24, 25 in the aortic wall was markedly increased in old AL versus young AL (Figure 5A and 5B). Further, aortic wall intima‐media gradient of PDGF‐BB was also markedly increased in old AL compared with young AL rats (Figure 5A and 5B).…”

Section: Resultsmentioning

confidence: 99%

“…The shift of aging VSMCs from a quiescent/contractile phenotype to an active synthetic phenotype is in response to proinflammation, a key molecular and cellular event that accelerates arterial intimal thickening, which is associated with PDGF signaling 21, 22, 24, 25, 40. The contractile proteins SM22α, α‐SMA, and myocardin are diminished in AL VSMCs with aging while PDGF is increased.…”

Section: Discussionmentioning

confidence: 99%

Calorie Restriction Curbs Proinflammation That Accompanies Arterial Aging, Preserving a Youthful Phenotype

Wang

Zhang

Zhu

et al. 2018

JAHA

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BackgroundAging exponentially increases the incidence of morbidity and mortality of quintessential cardiovascular disease mainly due to arterial proinflammatory shifts at the molecular, cellular, and tissue levels within the arterial wall. Calorie restriction (CR) in rats improves arterial function and extends both health span and life span. How CR affects the proinflammatory landscape of molecular, cellular, and tissue phenotypic shifts within the arterial wall in rats, however, remains to be elucidated.Methods and ResultsAortae were harvested from young (6‐month‐old) and old (24‐month‐old) Fischer 344 rats, fed ad libitum and a second group maintained on a 40% CR beginning at 1 month of age. Histopathologic and morphometric analysis of the arterial wall demonstrated that CR markedly reduced age‐associated intimal medial thickening, collagen deposition, and elastin fractionation/degradation within the arterial walls. Immunostaining/blotting showed that CR effectively prevented an age‐associated increase in the density of platelet‐derived growth factor, matrix metalloproteinase type II activity, and transforming growth factor beta 1 and its downstream signaling molecules, phospho‐mothers against decapentaplegic homolog‐2/3 (p‐SMAD‐2/3) in the arterial wall. In early passage cultured vascular smooth muscle cells isolated from AL and CR rat aortae, CR alleviated the age‐associated vascular smooth muscle cell phenotypic shifts, profibrogenic signaling, and migration/proliferation in response to platelet‐derived growth factor.Conclusions CR reduces matrix and cellular proinflammation associated with aging that occurs within the aortic wall and that are attributable to platelet‐derived growth factor signaling. Thus, CR reduces the platelet‐derived growth factor–associated signaling cascade, contributing to the postponement of biological aging and preservation of a more youthful aortic wall phenotype.

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“…The promoter activity of KLF8 was also reduced by the pretreatment of TNFα and platelet-derived growth factor (PDGF) (Figs. 1B and 1C), which is known as an inducer of phenotypic change [21]. TNFα-induced down regulation of KLF8 promoter activity was significantly blocked by the inhibition of ERK signaling pathway, whereas the inhibition of p38 MAPK pathway had no effect (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…For example, the contractile phenotype of VSMC is markedly converted into the synthetic phenotype by the simulation with platelet-derived growth factor (PDGF) [21]. On the other hand, insulin, insulin-like growth factor-1 (IGF-1), and laminin-mediated integrin signaling pathways stimulate the phenotypic switch, from the synthetic type to the contractile type [202324].…”

Section: Discussionmentioning

confidence: 99%

Regulation of vascular smooth muscle phenotype by cross-regulation of krüppel-like factors

Yun

Jin

et al. 2017

Korean J Physiol Pharmacol

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Regulation of vascular smooth muscle cell (VSMC) phenotype plays an essential role in many cardiovascular diseases. In the present study, we provide evidence that krüppel-like factor 8 (KLF8) is essential for tumor necrosis factor α (TNFα)-induced phenotypic conversion of VSMC obtained from thoracic aorta from 4-week-old SD rats. Stimulation of the contractile phenotype of VSMCs with TNFα significantly reduced the VSMC marker gene expression and KLF8. The gene expression of KLF8 was blocked by TNFα stimulation in an ERK-dependent manner. The promoter region of KLF8 contained putative Sp1, KLF4, and NFκB binding sites. Myocardin significantly enhanced the promoter activity of KLF4 and KLF8. The ectopic expression of KLF4 strongly enhanced the promoter activity of KLF8. Moreover, silencing of Akt1 significantly attenuated the promoter activity of KLF8; conversely, the overexpression of Akt1 significantly enhanced the promoter activity of KLF8. The promoter activity of SMA, SM22α, and KLF8 was significantly elevated in the contractile phenotype of VSMCs. The ectopic expression of KLF8 markedly enhanced the expression of SMA and SM22α concomitant with morphological changes. The overexpression of KLF8 stimulated the promoter activity of SMA. Stimulation of VSMCs with TNFα enhanced the expression of KLF5, and the promoter activity of KLF5 was markedly suppressed by KLF8 ectopic expression. Finally, the overexpression of KLF5 suppressed the promoter activity of SMA and SM22α, thereby reduced the contractility in response to the stimulation of angiotensin II. These results suggest that cross-regulation of KLF family of transcription factors plays an essential role in the VSMC phenotype.

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Platelet-derived growth factor regulates vascular smooth muscle phenotype via mammalian target of rapamycin complex 1

Cited by 47 publications

References 23 publications

Transdifferentiation of human endothelial progenitors into smooth muscle cells

Transdifferentiation of human endothelial progenitors into smooth muscle cells

Calorie Restriction Curbs Proinflammation That Accompanies Arterial Aging, Preserving a Youthful Phenotype

Regulation of vascular smooth muscle phenotype by cross-regulation of krüppel-like factors

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