Abstract
BackgroundCigarette smoke induced oxidative stress has been shown to reduce silent information regulator 1 (Sirt1) levels in lung tissue from smokers and patients with COPD patients. Sirt1 is known to inhibit endothelial senescence and may play a protective role in vascular cells. Endothelial progenitor cells (EPCs) are mobilized into circulation under various pathophysiological conditions, and are thought to play an important role in tissue repair in chronic obstructive lung disease (COPD). Therefore, Sirt1 and EPC-associated mRNAs were measured in blood samples from patients with COPD and from cultured CD34+ progenitor cells to examine whether these genes are associated with COPD development.MethodsThis study included 358 patients with a smoking history of more than 10 pack-years. RNA was extracted from blood samples and from CD34+ progenitor cells treated with cigarette smoke extract (CSE), followed by assessment of CD31, CD34, Sirt1 mRNA, miR-34a, and miR-126-3p expression by real-time RT-PCR.ResultsThe expression of CD31, CD34, Sirt1 mRNAs, and miR-126-3p decreased and that of miR-34a increased in moderate COPD compared with that in control smokers. However, no significant differences in these genes were observed in blood cells from patients with severe COPD compared with those in control smokers. CSE significantly decreased Sirt1 and increased miR-34a expression in cultured progenitor cells.ConclusionSirt1 expression in blood cells from patients with COPD could be a biomarker for disease stability in patients with moderate COPD. MiR-34a may participate in apoptosis and/or senescence of EPCs in smokers. Decreased expression of CD31, CD34, and miR-126-3p potentially represents decreased numbers of EPCs in blood cell from patients with COPD.
Highlights
Cigarette smoke induced oxidative stress has been shown to reduce silent information regulator 1 (Sirt1) levels in lung tissue from smokers and patients with chronic obstructive pulmonary disease (COPD) patients
We examined Endothelial progenitor cells (EPCs)-related gene expression in blood cells from smokers, and found that the expression of circulating CD31, CD34, Sirt1 genes, and miR-126-3p was decreased and that of miR-34a was increased in patients with moderate COPD when compared with non-COPD subjects
We found a positive correlation between CD31 and Sirt1 mRNA expression, and confirmed the upregulation of p21 mRNA and miR-34a, and the downregulation of Sirt1 expression by exposure to cigarette smoke extract (CSE) in cultured CD34+ progenitor cells
Summary
Cigarette smoke induced oxidative stress has been shown to reduce silent information regulator 1 (Sirt1) levels in lung tissue from smokers and patients with COPD patients. Endothelial progenitor cells (EPCs) are mobilized into circulation under various pathophysiological conditions, and are thought to play an important role in tissue repair in chronic obstructive lung disease (COPD). Numerous studies have indicated the presence of endothelial dysfunction in smokers and in patients with COPD [1, 2], and have suggested that reduced numbers and/ or dysfunction of endothelial progenitor cells (EPCs) could contribute to the tissue angiogenesis and repair. In the context of EPCs and miRNA, Zhao et al, reported that miR-34a impairs EPC-mediated angiogenesis by inhibiting Sirt in rats [16], indicating that oxidative stress-induced p53 and miR-34a expression could induce vascular endothelial cell senescence and decrease EPC activity through Sirt inhibition. The precursor miRNA (pre-miR-126) produces two mature strands, miR-126-3p and miR-126-5p [24]; administration of miR-126-3p has been shown to promote the incorporation of Sca-1+ progenitor cells [27], suggesting an essential role for miR-126 in the endothelial stress response and the release of EPCs
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