Angiotensin II-Induced Long Non-Coding RNA Alivec Regulates Chondrogenesis in Vascular Smooth Muscle Cells

Cells

Marpadga A. Reddy¹  Vishnu Amaram Samara¹  Rama Natarajan¹  Kenneth Stapleton¹  Sadhan Das¹  Rituparna Ganguly¹  Linda Lanting¹  Amy Leung¹  Vinay Singh Tanwar¹  Maryam Abdollahi¹ 

[1] Department of Diabetes Complications and Metabolism, Arthur Riggs Diabetes and Metabolism Research Institute, Duarte, CA 91010, USA;

关键词: Angiotensin II;    lncRNAs;    cardiovascular disease;    vascular smooth muscle cells;    chondrocytes;    hypertension;   

DOI  :  10.3390/cells10102696

来源: DOAJ

【 摘 要 】

Long non-coding RNAs (lncRNAs) play key roles in Angiotensin II (AngII) signaling but their role in chondrogenic transformation of vascular smooth muscle cells (VSMCs) is unknown. We describe a novel AngII-induced lncRNA Alivec (Angiotensin II-induced lncRNA in VSMCs eliciting chondrogenic phenotype) implicated in VSMC chondrogenesis. In rat VSMCs, Alivec and the nearby gene Acan, a chondrogenic marker, were induced by growth factors AngII and PDGF and the inflammatory cytokine TNF-α. AngII co-regulated Alivec and Acan through the activation of AngII type1 receptor signaling and Sox9, a master transcriptional regulator of chondrogenesis. Alivec knockdown with GapmeR antisense-oligonucleotides attenuated the expression of AngII-induced chondrogenic marker genes, including Acan, and inhibited the chondrogenic phenotype of VSMCs. Conversely, Alivec overexpression upregulated these genes and promoted chondrogenic transformation. RNA-pulldown coupled to mass-spectrometry identified Tropomyosin-3-alpha and hnRNPA2B1 proteins as Alivec-binding proteins in VSMCs. Furthermore, male rats with AngII-driven hypertension showed increased aortic expression of Alivec and Acan. A putative human ortholog ALIVEC, was induced by AngII in human VSMCs, and this locus was found to harbor the quantitative trait loci affecting blood pressure. Together, these findings suggest that AngII-regulated lncRNA Alivec functions, at least in part, to mediate the AngII-induced chondrogenic transformation of VSMCs implicated in vascular dysfunction and hypertension.

【 授权许可】

Unknown