Abstract 56: Proteome Profile Of Vascular Smooth Muscle Cells During Phenotypic Switching In Human Hypertension

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Livia L Camargo ◽  
Sheon Mary ◽  
Sergio Lilla ◽  
Sara Zanivan ◽  
Neil Bulleid ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle Cells ◽  
Proteomic Analysis ◽  
Fold Change ◽  
Phenotypic Switching ◽  
Tandem Mass ◽  
Human Hypertension ◽  
Ecm Proteins ◽  
Proteome Profile ◽  
In Cells

Vascular smooth muscle cells (VSMCs) are key players in vascular dysfunction associated with hypertension, where phenotypic switch is a fundamental process. While various transcription factors have been implicated in this process, the proteomic signature associated with phenotypic switching in human hypertension is unknown. Using high fidelity proteomic analysis, we characterized the proteome profile of VSMC in human hypertension. VSMC derived from resistance arteries from normotensive (NT) and hypertensive (HT) subjects were studied. Protein expression and cell migration were assessed by immunoblotting and wound healing assay. VSMC proteins were labelled with isobaric tandem mass tags and identified by liquid chromatography tandem mass spectrometry. The oxidative proteome was assessed using stable isotope-labelled iodoacetamide to target free reduced cysteine thiols. VSMCs from HT subjects exhibit reduced expression of α-SMA (0.05±0.01 vs NT:0.20±0.03, p<0.05), increased expression of the proliferation marker, PCNA (0.162±0.3 vs NT:0.51±0.004, p<0.05), and increased migration (54.68±2.86 vs NT:23.37±8.36, p<0.05). The proteomic analysis identified 207 proteins upregulated in HT subjects (fold change>1.5, p<0.05). There were no changes in protein expression of pathways related to the contractile phenotype (MYH11, CNN1, TAGLN, TPM, CALD1). However, extracellular matrix (ECM) proteins such as COL1A1, COL9A1, COL10A1, FBN1, FBLN1 were increased in cells from HT (fold change>1.5, p<0.05), suggesting a switch to a fibroblast-like phenotype in hypertension. Expression of proteins related to the interferon and IL-1β pathways (IFIT1, IFIT2, IFIT3, MX1, MX2, ABCA1, ABCA2, IL1RAP, CD36, ICAM1) were also increased in cells from HT subjects (fold change>1.5, p<0.05). Considering the importance of oxidative stress in hypertension, we assessed the VSMC oxidative proteome. Results demonstrate that ECM proteins, such as COL11A1 and COL16A1, were highly oxidized in cells from HT (fold change>1.5, p<0.05). Our study provides new insights into the proteomic changes that define the vascular phenotype in hypertension and highlights candidate targets that may drive phenotypic switching associated with vascular injury in hypertension.

scholarly journals TRPC6 regulates phenotypic switching of vascular smooth muscle cells through plasma membrane potential‐dependent coupling with PTEN

2019 ◽  
Vol 33 (9) ◽  
pp. 9785-9796 ◽  
Author(s):  
Takuro Numaga‐Tomita ◽  
Tsukasa Shimauchi ◽  
Sayaka Oda ◽  
Tomohiro Tanaka ◽  
Kazuhiro Nishiyama ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Plasma Membrane ◽  
Membrane Potential ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Phenotypic Switching ◽  
Plasma Membrane Potential

Micro-RNA Regulation of Vascular Smooth Muscle Cells and Its Significance in Cardiovascular Diseases

2021 ◽  
Author(s):  
Duong Ngoc Diem Nguyen ◽  
William M Chilian ◽  
Shamsul Mohd Zain ◽  
Muhammad Fauzi Daud ◽  
Yuh Fen Pung
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Intracellular Signaling ◽  
Neointimal Hyperplasia ◽  
Muscle Cells ◽  
Micro Rna ◽  
Phenotypic Switching ◽  
Micro Rnas

Cardiovascular disease (CVD) is among the leading causes of death worldwide. Micro-RNAs (miRNAs), regulatory molecules that repress protein expression, have attracted considerable attention in CVD research. The vasculature plays a big role in CVD development and progression and dysregulation of vascular cells underlies the root of many vascular diseases. This review provides a brief introduction of the biogenesis of miRNAs and exosomes, followed by overview of the regulatory mechanisms of miRNAs in vascular smooth muscle cells (VSMCs) intracellular signaling during phenotypic switching, senescence, calcification and neointimal hyperplasia. Evidence of extracellular signaling of VSMCs and other cells via exosomal and circulating miRNAs was also presented. Lastly, current drawbacks and limitations of miRNA studies in CVD research and potential ways to overcome these disadvantages were discussed in detail. In-depth understanding of VSMC regulation via miRNAs will add substantial knowledge and advance research in diagnosis, disease progression and/or miRNA-derived therapeutic approaches in CVD research.

scholarly journals MicroRNA-143/-145 in Cardiovascular Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Wang Zhao ◽  
Shui-Ping Zhao ◽  
Yu-Hong Zhao
Keyword(s):  
Smooth Muscle ◽  
Cardiovascular Diseases ◽  
Vascular Smooth Muscle Cells ◽  
Essential Role ◽  
Recent Progress ◽  
Potential Role ◽  
Phenotypic Switching ◽  
Diagnostic Biomarkers ◽  
Potential Strategy

MicroRNAs (miRNAs) play an essential role in the onset and development of many cardiovascular diseases. Increasing evidence shows that miRNAs can be used as potential diagnostic biomarkers for cardiovascular diseases, and miRNA-based therapy may be a promising therapy for the treatment of cardiovascular diseases. The microRNA-143/-145 (miR-143/-145) cluster is essential for differentiation of vascular smooth muscle cells (VSMCs) and determines VSMC phenotypic switching. In this review, we summarize the recent progress in knowledge concerning the function of miR-143/-145 in the cardiovascular system and their role in cardiovascular diseases. We discuss the potential role of miR-143/-145 as valuable biomarkers for cardiovascular diseases and explore the potential strategy of targeting miR-143 and miR-145.

scholarly journals MicroRNA regulation of BMP signaling; cross-talk between endothelium and vascular smooth muscle cells

2018 ◽  
Author(s):  
Charlene Watterston ◽  
Lei Zeng ◽  
Abidemi Onabadejo ◽  
Sarah J Childs
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Vascular Function ◽  
Muscle Cells ◽  
Phenotypic Switching ◽  
Vascular Stability ◽  
Bmp Signalling

AbstractVascular smooth muscle cells (vSMC) are essential to the integrity of blood vessels, and therefore an attractive target of therapeutics aimed at improving vascular function. Smooth muscle cells are one of the few cell types that maintain plasticity and can switch phenotypes from differentiated (contractile) to de-differentiated (synthetic) and vice versa. As small regulatory transcripts, miRNAs act as genetic ‘fine tuners’ of posttranscriptional events and can act as genetic switches promoting phenotypic switching. The microRNAmiR26atargets the BMP signalling effector,smad1. We show that loss ofmiR26leads to hemorrhage (a loss of vascular stability)in vivo, suggesting altered vascular differentiation. Reduction inmiR26alevels increasessmad1mRNA and phospho-Smad1 (pSmad1) levels. We show that increasing BMP signalling by overexpression ofsmad1also leads to hemorrhage and that normalization of Smad1 levels through double knockdown ofmiR26andsmad1rescues hemorrhage suggesting a direct relationship betweenmiR26andsmad1and vascular stability. Using a BMP genetic reporter and pSmad1 staining we show that the effect ofmiR26on vascular instability is non-autonomous; BMP signalling is active in embryonic endothelial cells, but not in smooth muscle cells. Nonetheless, increased BMP signalling due to loss ofmiR26results in an increase inacta2-expressing smooth muscle cell numbers and promotes a differentiated smooth muscle morphology. Taken together our data suggests thatmiR26modulates BMP signalling in endothelial cells and indirectly promotes a differentiated smooth muscle phenotype. Our data also suggests that crosstalk from BMP-responsive endothelium to smooth muscle is important for its differentiation.

scholarly journals Akt/eNOS and MAPK Signaling Pathways Mediated the Phenotypic Switching of Thoracic Aorta Vascular Smooth Muscle Cells in Aging/Hypertensive Rats

2018 ◽  
pp. 543-553 ◽  
Author(s):  
L. ZHANG ◽  
Z. XU ◽  
Y. WU ◽  
J. LIAO ◽  
F. ZENG ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Western Blot ◽  
Smooth Muscle Cells ◽  
Thoracic Aorta ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Mapk Signaling ◽  
Phenotypic Switching ◽  
Hypertensive Rats

Considerable evidence demonstrates that phenotypic switching of vascular smooth muscle cells (VSMCs) is influenced by aging and hypertension. During phenotypic switching, VSMCs undergo a switch to a proliferative and migratory phenotype, with this switch being a common pathology in cardiovascular diseases. The aim of this study was to explore the joint influence of age and hypertension on thoracic aortic smooth muscle phenotypic switching and the balance of Akt and mitogen-activated protein kinase (MAPK) signaling during this switch. Different ages of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were used to establish hypertension and aging models. The phenotypic state was determined by detecting the marker proteins α-SM-actin, calponin, and osteopontin (OPN) via immunohistochemical staining and Western blot. Signaling proteins associated with the Akt and MAPK pathways were detected in rat thoracic aorta using Western blot. Both aging and hypertension caused a decrease in contractile (differentiated) phenotype markers (α-SM-actin and calponin), while the synthetic (proliferative or de-differentiated) phenotype maker was elevated (OPN). When combining hypertension and aging, this effect was enhanced, with Akt signaling decreased, while MAPK signaling was increased. These results suggested that VSMCs phenotype switching is modulated by a balance between Akt and MAPK signaling in the process of aging and hypertension.

Sign in / Sign up

Export Citation Format

Share Document