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 important 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 plus the nearby gene Acan, a chondrogenic marker, have been induced by development components AngII and PDGF plus 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, 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. Additionally, 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 identified to harbor the quantitative trait loci affecting blood stress. Collectively, these findings recommend that AngII-regulated lncRNA Alivec functions, no less than in portion, to mediate the AngII-induced chondrogenic transformation of VSMCs implicated in vascular dysfunction and hypertension. Keywords: 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 Bioactive Compound Library site diseases (CVDs), like hypertension and atherosclerosis, are major causes of morbidity and mortality worldwide [1]. Vascular smooth muscle cells (VSMCs) inside the arterial wall maintain vascular tone and blood stress and are beneath the handle from the renin ngiotensin technique (RAS)-Angiotensin II (AngII) technique. AngII, the principal effector on the RAS pathway, is 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 elevated VSMC proliferation, hypertrophy, migration, inflammation and the crucial processes linked with the pathogenesis of arterial stenosis/restenosis, hypertension and atherosclerosis [4]. Additionally, the synthetic VSMCs are likely to transformCopyright: 2021 by the authors. Licensee MDPI, Basel, Switzerland. This short CX-5461 Cancer article is an open access short article distributed below the terms and conditions from the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).Cells 2021, ten, 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 related with these pathologies [80]. Aggrecan (Acan) is an extracellular matrix protein t.