MicroRNAs as Potential Mediators for Cigarette Smoking Induced Atherosclerosis

Abstract

Smoking increases the risk of atherosclerosis-related events, such as myocardial infarction and ischemic stroke. Recent studies have examined the expression levels of altered microRNAs (miRNAs) in various diseases. The profiles of tissue miRNAs can be potentially used in diagnosis or prognosis. However, there are limited studies on miRNAs following exposure to cigarette smoke (CS). The present study was designed to dissect the effects and cellular/molecular mechanisms of CS-induced atherosclerogenesis. Apolipoprotein E knockout (ApoE KO) mice were exposed to CS for five days a week for two months at low (two puffs/min for 40 min/day) or high dose (two puffs/min for 120 min/day). We measured the area of atherosclerotic plaques in the aorta, representing the expression of miRNAs after the exposure period. Two-month exposure to the high dose of CS significantly increased the plaque area in aortic arch, and significantly upregulated the expression of atherosclerotic markers (VCAM-1, ICAM-1, MCP1, p22phox, and gp91phox). Exposure to the high dose of CS also significantly upregulated the miRNA-155 level in the aortic tissues of ApoE KO mice. Moreover, the expression level of miR-126 tended to be downregulated and that of miR-21 tended to be upregulated in ApoE KO mice exposed to the high dose of CS, albeit statistically insignificant. The results suggest that CS induces atherosclerosis through increased vascular inflammation and NADPH oxidase expression and also emphasize the importance of miRNAs in the pathogenesis of CS-induced atherosclerosis. Our findings provide evidence for miRNAs as potential mediators of inflammation and atherosclerosis induced by CS.

Gene Expression and Epigenetic Changes in Mice Following Inhalation of Copper(II) Oxide Nanoparticles

“…Specifically, the expression of mmu-miR-21a-5p, mmu-miR-147-3p, mmu-miR-449a-5p, and mmu-miR-703 was deregulated in the lungs of mice exposed to multi-walled carbon nanotubes [24] and mmu-miR-342-3p in mice exposed to nano-TiO2 particles [25]. The deregulation of the miRNAs observed in our study was further found in the lungs of mice after cigarette smoke exposure (mmu-miR-21a-5p, mmu-miR-135b-5p, mmu-miR-146a-5p, mmu-miR-146b-5p, mmu-miR-155-5p, mmu-miR-342-3p, mmu-miR-449a-5p, mmu-miR-489-3p, and mmu-miR-672-5p) [26], in mice with cigarette smoke induced atherosclerosis (mmu-miR-21a-5p and mmu-miR-155-5p) [27], in the lungs of mice after radon inhalation (mmu-miR-21a-3p, mmu-miR-135b-5p, mmu-miR-146b-5p, mmu-miR-1298-5p, mmu-miR-6972-5p, and mmu-miR-703) [28], in mice with lung tumors (mmu-miR-135b-5p, mmu-miR-146b-5p, mmu-miR-223-3p, and mmu-miR-1298-5p) [29][30][31], in an ovalbumin-induced asthma mouse model (mmu-miR-21a-5p, mmu-miR-135b-5p, mmu-miR-146a-5p, mmu-miR-155-5p, mmu-miR-223-3p, and mmu-miR-451a) [32], and in mice with pneumonia and influenza infections (mmu-miR-21a-5p, mmu-miR-144-5p, mmu-miR-155-5p, and mmu-miR-223-3p) [33][34][35]. This overall suggests that the inhalation of CuO NPs induces a similar response as the above-mentioned adverse conditions and therefore likely has negative effects on the organism.…”

Proteomic identification of the proteins related to cigarette smoke-induced cardiac hypertrophy in spontaneously hypertensive rats

“…Rats were exposed to CS at low (2 puffs/min for 40 min/day) or high dose (2 puffs/min for 120 min/day) (n = 7 per group) for 5 days a week for 2 months. The CS inhalation was conducted using unfiltered research cigarette 3R4F (Tabacco Health Research Institute, Kentucky University, Lexington, KY) and the Tabacco Smoke Inhalation Experiment System for small animals (Model SIS-CS; Shibata Scientific Technology, Tokyo, Japan) 44 . The smoke generator automatically generated CS by setting the volume of the syringe pump and the number of puffs per minutes.…”

Lycopene Inhibits Smoke-Induced Chronic Obstructive Pulmonary Disease and Lung Carcinogenesis by Modulating Reverse Cholesterol Transport in Ferrets

“…We found a lower mRNA expression of LXRa, PPARa, and ABCA1/G1 followed by TC accumulation in the NNK/CS group compared with the control group in lungs. Although the mechanism(s) underlying lower expression of PPARa, LXRa, and its target genes in lungs after NNK/CS exposure remains unclear, previous studies reported an increased expression of micro-RNAs (e.g., miRNA-21, miRNA-155, and miRNA-20), which target PPARa/LXRa and ABCA1/G1, after CS exposure (44,45). These findings could help us to explain the downregulation of mRNA expression of PPARa/LXRa and ABCA1/G1 after NNK/CS exposure, but future studies (such as miRNA analysis) are required.…”