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: Extended non-coding RNAs (lncRNAs) play crucial roles in Angiotensin II (AngII) signaling but their part 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 as well as the nearby gene Acan, a chondrogenic marker, had been induced by growth factors AngII and PDGF as well as the inflammatory cytokine TNF-. AngII co-regulated Alivec and Acan via 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, which includes 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. In addition, male rats with AngIIdriven hypertension showed Sordarin medchemexpress improved aortic expression of Alivec and Acan. A putative human ortholog ALIVEC, was induced by AngII in human VSMCs, and this locus was identified to harbor the quantitative trait loci affecting blood pressure. With each other, these findings suggest that AngII-regulated lncRNA Alivec functions, no less than in aspect, to mediate the AngII-induced chondrogenic transformation of VSMCs implicated in vascular dysfunction and hypertension. Search phrases: Angiotensin II; lncRNAs; cardiovascular disease; 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 ailments (CVDs), for example hypertension and atherosclerosis, are major causes of morbidity and mortality worldwide [1]. Vascular smooth muscle cells (VSMCs) in the arterial wall keep vascular tone and blood stress and are below the control with the renin ngiotensin system (RAS)-Angiotensin II (AngII) method. AngII, the Diethyl phthalate-d10 custom synthesis principal effector in the RAS pathway, is often 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 development 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, inflammation along with the crucial processes linked 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 an open access post distributed below the terms and circumstances of your Creative 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,two ofinto chondrocyte-like cells, which promotes extracellular calcium deposition and vascular dysfunction associated with these pathologies [80]. Aggrecan (Acan) is an extracellular matrix protein t.