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

S. Cells 2021, ten, 2696. https://doi.org/10.3390/ cells10102696 Academic Editor: Raj Kishore Received: 16 September 2021 Accepted: five October 2021 Published: 9 OctoberAbstract: Long non-coding RNAs (lncRNAs) play essential roles in Angiotensin II (AngII) signaling but their function in chondrogenic transformation of vascular smooth muscle cells (VSMCs) is unknown. We describe a novel AngII-induced lncRNA Butoconazole Biological Activity Alivec (Angiotensin II-induced lncRNA in VSMCs eliciting chondrogenic phenotype) implicated in VSMC chondrogenesis. In rat VSMCs, Alivec plus the nearby gene Acan, a chondrogenic marker, had been induced by development things AngII and PDGF and the inflammatory cytokine TNF-. AngII co-regulated Alivec and Acan by way 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, such as 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. Moreover, male rats with AngIIdriven hypertension showed elevated aortic expression of Alivec and Acan. A putative human ortholog ALIVEC, was induced by AngII in human VSMCs, and this locus was discovered to harbor the quantitative trait loci affecting blood pressure. Together, these findings suggest that AngII-regulated lncRNA Alivec functions, at least in portion, to mediate the AngII-induced chondrogenic transformation of VSMCs implicated in vascular dysfunction and hypertension. Key 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), including hypertension and atherosclerosis, are top causes of morbidity and mortality worldwide [1]. Vascular smooth muscle cells (VSMCs) in the arterial wall keep vascular tone and blood pressure and are beneath the manage on the renin ngiotensin method (RAS)-Angiotensin II (AngII) PKC| program. AngII, the major effector from the RAS pathway, can be a potent vasoconstrictor and regulator of blood stress. Dysregulation of RAS or abnormal AngII signaling is implicated in hypertension and atherosclerosis [2]. In CVD or vascular injury, dysregulated growth aspect and AngII signaling promotes VSMCs to switch from a contractile to synthetic phenotype [3]. The synthetic phenotype manifests in increased VSMC proliferation, hypertrophy, migration, inflammation plus the important processes linked with the pathogenesis of arterial stenosis/restenosis, hypertension and atherosclerosis [4]. Moreover, the synthetic VSMCs tend to transformCopyright: 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access post distributed beneath the terms and circumstances in the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ four.0/).Cells 2021, ten, 2696. https://doi.org/10.3390/cellshttps://www.mdpi.com/journal/cellsCells 2021, 10,2 ofinto chondrocyte-like cells, which promotes extracellular calcium deposition and vascular dysfunction linked with these pathologies [80]. Aggrecan (Acan) is an extracellular matrix protein t.