Abstract
Atherosclerosis (AS) is a chronic disease of the arterial wall. The role of lncRNAs in AS has been acknowledged. This study investigated the role of lncRNA plasmacytoma variant translocation 1 (PVT1) in AS via the MAPK/NF-κB pathway. Serum samples were collected from AS and non-AS patients. Serum levels of PVT1, CRP, IL-6, IL-1β, and TNF-α were determined. AS mouse model was established and transfected with si-PVT1. Levels of TG, TC, HDL, LDL, MAPK, NF-κB, MMP-2, MMP-9, TIMP-1, and macrophage content were detected. Human arterial vascular smooth muscle cells (HA-VSMCs) induced by 50 mg/mL oxLDL were transfected with si-PVT1 or oe-PVT1 and added with MAPK inhibitor U0126. Viability, apoptosis, cell cycle, colony formation and DNA replication were assessed. Levels of apoptosis-related proteins were detected. Consequently, PVT1 was highly expressed in AS patients. Silencing PVT1 decreased levels of TG, TC, LDL, IL-6, IL-1β, TNF-α, MMP-2, MMP-9, CRP, TIMP-1, MAPK, and NF-κB, increased HDL, reduced atherosclerotic plaques and macrophage content in mice, inhibited viability, clones and EdU positive rates in HA-VSMCs, but promoted apoptosis and cell cycle arrest. Inhibition of MAPK/NF-κB pathway suppressed proliferation and promoted apoptosis of HA-VSMCs while PVT1 overexpression facilitated AS development. Briefly, silencing PVT1 inhibited AS development by downregulating MAPK/NF-κB pathway.
Highlights
Atherosclerosis (AS) is manifested with chronic inflammation and dysfunction in the vascular system, which may cause severe consequences such as sudden cardiac death, myocardial infarction, peripheral thromboses and stroke [1]
We implemented a study to explore how Long noncoding RNAs (lncRNAs) plasmacytoma variant translocation 1 (PVT1) acts on AS by regulating the mitogenactivated protein kinase (MAPK)/nuclear factor-κB (NF-κB) pathway with the expectation to seek out novel clinical value for AS patients
LncRNAs exert www.aging-us.com essential functions on vascular inflammatory response and metabolism in endothelial cells and macrophages, suggestive of the possible effects of lncRNAs on AS development [23]
Summary
Atherosclerosis (AS) is manifested with chronic inflammation and dysfunction in the vascular system, which may cause severe consequences such as sudden cardiac death, myocardial infarction, peripheral thromboses and stroke [1]. The treatment approaches for AS include limiting the hazard factors like hyperlipemia or high blood pressure and regulating inflammatory responses, among which regulating inflammatory response is still under development in the blood vessels [4]. Long noncoding RNAs (lncRNAs), normally defined as a set of transcripts with the length of more than 200 nucleotides without any protein-coding ability [5], are engaged in manipulating diverse cellular processes [6], vascular wall function, macrophage activation, lipid metabolism and inflammatory responses [7]. LncRNA PVT1 functions as an independent hazard factor for coronary AS progression and is highly expressed in AS patients [9], but the exact mechanism is still unclear. We implemented a study to explore how lncRNA PVT1 acts on AS by regulating the MAPK/NF-κB pathway with the expectation to seek out novel clinical value for AS patients
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