Abstract 17190: Circulating MicroRNA-126 as a Potential Biomarker for Recovery from Smoking-Related Endothelial Damage
Background: Cigarette smoking promotes vascular endothelial damage and accelerates progression of atherosclerosis. Numerous efforts have been made to identify reliable and predictive biomarkers to detect the early signs of recovery from smoking-induced endothelial damage. We hypothesized that the expression of vascular endothelium-enriched microRNA (miRNA) would serve as a novel biomarker for recovery from smoking-related endothelial damage in middle-aged habitual smokers.
Methods: Apparently healthy male smokers (n=21, 40±7 years) were enrolled and instructed to stop smoking. Their clinical profiles including endothelial function and laboratory findings including endothelium-enriched miRNA were investigated before and after 8 weeks of smoking cessation. Serum levels of cotinine, metabolites of nicotine, were measured to confirm smoking cessation. Plasma levels of sphingosine 1-phosphate (S1P) and dihydrosphingosine 1-phosphate (DHS1P) were measured by HPLC after fluorescent derivatization with o-phthaldialdehyde. Endothelial function was assessed by reactive hyperemia of peripheral arterial tonometry (PAT) using End-PAT 2000. The expression of miRNA in plasma was analyzed by quantitative real-time PCR.
Results: Among measured miRNAs, plasma miRNA-122 (miR-122) and miRNA-126 (miR-126) positively correlated with plasma DHS1P, a pro-survival molecule in endothelium (r=0.568, P<0.01; and r=0.488, P<0.05; respectively) but not correlated with plasma S1P. After 8 weeks, smokers who completely attained smoking cessation indicated significantly increased PAT ratio (from 0.26±0.09 to 0.31±0.13, P<0.05) and plasma miR-126 (from 0.017±0.006 to 0.029±0.018 U, P<0.05).
Conclusions: This is the first report to show that plasma level of miR-126 increases rapidly after 8 weeks smoking cessation with concomitant improvement of endothelial function. These findings suggested a potential use of miR-126 as a sensitive and informative biomarker for recovery from smoking-induced endothelial damage. MiR-126 might have a protective influence on the endothelium, and the quantitative assessment of miR-126 in plasma might have diagnostic potential to detect early recovery of endothelial function particularly in habitual smokers.
- © 2012 by American Heart Association, Inc.