Abstract
BackgroundMicroRNAs control gene expression by post-transcriptional inhibition. Dysregulation of the expressions of miR-199a/214 cluster has been linked to cardiovascular diseases. This study aimed at identifying potential microRNAs related to vascular senescence.MethodsSeven candidate microRNAs (miR-19a, −20a, −26b, −106b, − 126, − 214, and − 374) related to cell proliferation were tested for their expressions under CoCl2-induced hypoxia in vascular smooth muscle cells (VSMCs). After identification of miR-214 as the candidate microRNA, telomere integrity impairment and cell cycle arrest were examined in VSMCs by using miR-214 mimic, AntagomiR, and negative controls. To investigate the clinical significance of miR-214 in vascular diseases, its plasma level from patients with carotid artery stenosis (CAS) was assessed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR).ResultsCoCl2 treatment for 48 h suppressed cell proliferation and angiogenesis as well as enhanced cell senescence in VSMCs. Besides, miR-214 level was elevated in both intracellular and exosome samples of VSMCs after CoCl2 treatment. Manipulating miR-214 in VSMCs demonstrated that miR-214 not only inhibited angiogenic and proliferative capacities but also promoted senescence through the suppression of quaking. Additionally, circulating miR-214 level was upregulated in CAS patients with high low-density lipoprotein cholesterol (LDL-C) value.ConclusionOur findings suggested that miR-214 plays a role in the modulation of VSMC angiogenesis, proliferation, and senescence with its plasma level being increased in CAS patients with elevated LDL-C value, implying that it may be a vascular senescence marker and a potential therapeutic target for vascular diseases.
Highlights
Despite therapeutic advances in cardiovascular disease, stroke remains the second leading cause of death worldwide as well as the third leading cause of disability and lost productivity (Mathers et al, 2017)
The results indicated that Cobalt chloride (CoCl2) treatment downregulated molecular expressions of anti-senescence markers, including those of TERT, TERF1 and TERF2 transcripts and TERF1 and TERF2 proteins (Fig. 2c-e)
Since previous evidence demonstrated that senescenceinducing signals usually involve either the p53 or the p16INK4-RB tumor suppressor pathways, we further investigated the expressions of cell cycle regulators (i.e., p16INK4, p21CIP1, phosphor-retinoblastoma protein (pRB)) after CoCl2 treatment
Summary
Despite therapeutic advances in cardiovascular disease, stroke remains the second leading cause of death worldwide as well as the third leading cause of disability and lost productivity (Mathers et al, 2017). There are two types of stroke, namely, ischemic stroke and hemorrhagic stroke. The former, which is attributed to a blood clot on an atherosclerotic plaque within a blood vessel in the brain that subsequently cuts off blood supply to that part of the brain, is the most common (Marulanda-Londono & Chaturvedi, 2016; Min et al, 1999; Rothwell, 2007). VSMC senescence in the fibrous cap is known to contribute to inefficient plaque repair that predisposes to subsequent plaque instability and rupture (Gorenne et al, 2006). MicroRNAs control gene expression by post-transcriptional inhibition. Dysregulation of the expressions of miR-199a/214 cluster has been linked to cardiovascular diseases. This study aimed at identifying potential microRNAs related to vascular senescence
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