AK098656, a Novel Vascular Smooth Muscle Cell-Dominant Long Noncoding RNA, Promotes HypertensionNovelty and Significance [Genetics]

Recent studies reported some long noncoding RNAs (lncRNAs)–mediated vascular smooth muscle cells (VSMCs) phenotypic switch, which was a common pathophysiological process of vascular diseases. However, whether human-specific expressed lncRNAs would modulate VSMCs phenotype and participate into the pathogenesis of essential hypertension remains unclear. By comparing the circulating lncRNAs expression profiles between hypertensive patients and healthy controls, we identified a lncRNA-AK098656, strongly upregulated in the plasma of hypertensive patients, and predominantly expressed in VSMCs. AK098656 promoted VSMCs synthetic phenotype evidenced by increasing VSMC proliferation and migration, elevating extracellular matrix proteins, whereas lowering contractile proteins. Furthermore, AK098656 was demonstrated to directly bind with the VSMCs-specific contractile protein, myosin heavy chain-11, and an essential component of extracellular matrix, fibronectin-1, and finally lowered these protein levels through protein degradation. AK098656 was also shown to bind with 26S proteasome non-ATPase regulatory subunit 11 and facilitated myosin heavy chain-11 to interact with this protein. In vivo, AK098656 transgenic rats showed spontaneous development of hypertension, with elevated VSMCs synthetic phenotype and narrowed resistant arteries. Transgenic rats also showed slight cardiac hypertrophy without other complications, which was similar with early pathophysiological changes of hyperten...

Source: Hypertension - January 10, 2018 Category: Cardiology Authors: Ling Jin, Xianjuan Lin, Lei Yang, Xiaofang Fan, Wenjie Wang, Shuangyue Li, Jing Li, Xiaoyan Liu, Minghui Bao, Xiao Cui, Jichun Yang, Qinghua Cui, Bin Geng, Jun Cai Tags: Biomarkers, Smooth Muscle Proliferation and Differentiation, Hypertension Original Articles Source Type: research