S. Cells 2021, 10, 2696. https://doi.org/10.3390/ cells10102696 Academic Editor: Raj Kishore Received: 16 September 2021

S. Cells 2021, 10, 2696. https://doi.org/10.3390/ cells10102696 Academic Editor: Raj Kishore Received: 16 September 2021 Accepted: 5 October 2021 Published: 9 OctoberAbstract: Extended non-coding RNAs (lncRNAs) play essential roles in Angiotensin II (AngII) signaling but their function in chondrogenic transformation of vascular smooth m-3M3FBS MedChemExpress 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 as well as the nearby gene Acan, a chondrogenic marker, were induced by growth variables AngII and PDGF along with the inflammatory cytokine TNF-. AngII co-regulated Alivec and Acan by means of 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 AngIIinduced 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 AngIIdriven 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. Collectively, these findings recommend that AngII-regulated lncRNA Alivec functions, at least in element, to mediate the AngII-induced chondrogenic transformation of VSMCs implicated in vascular dysfunction and hypertension. Keyword phrases: Angiotensin II; lncRNAs; cardiovascular illness; vascular smooth muscle cells; chondrocytes; hypertensionPublisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.1. Introduction Cardiovascular diseases (CVDs), such as hypertension and atherosclerosis, are leading causes of morbidity and mortality worldwide [1]. Vascular smooth muscle cells (VSMCs) inside the arterial wall preserve vascular tone and blood stress and are below the manage of the renin ngiotensin technique (RAS)-Angiotensin II (AngII) method. AngII, the primary effector of your RAS pathway, is really a potent vasoconstrictor and regulator of blood pressure. Dysregulation of RAS or abnormal AngII signaling is implicated in hypertension and atherosclerosis [2]. In CVD or vascular injury, dysregulated growth factor and AngII signaling promotes VSMCs to switch from a contractile to synthetic phenotype [3]. The synthetic phenotype manifests in enhanced VSMC proliferation, hypertrophy, migration, Taurohyodeoxycholic acid Protocol inflammation plus the important processes connected together with the pathogenesis of arterial stenosis/restenosis, hypertension and atherosclerosis [4]. Moreover, the synthetic VSMCs are likely to transformCopyright: 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is definitely an open access article distributed below the terms and conditions of the Inventive Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).Cells 2021, 10, 2696. https://doi.org/10.3390/cellshttps://www.mdpi.com/journal/cellsCells 2021, ten,2 ofinto chondrocyte-like cells, which promotes extracellular calcium deposition and vascular dysfunction connected with these pathologies [80]. Aggrecan (Acan) is definitely an extracellular matrix protein t.