Sirt1 expression is associated with CD31 expression in blood cells from patients with chronic obstructive pulmonary disease

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.

SIRT1 and SIRT6 Signaling Pathways in Cardiovascular Disease Protection

“…A recent study including 358 patients with a smoking history of >10 pack-years showed decreased SIRT1 mRNA levels and number of EPCs (85).…”

Nucleosides isolated from <em>Ophiocordyceps sinensis</em> inhibit cigarette smoke extract-induced inflammation via the SIRT1&ndash;nuclear factor-&kappa;B/p65 pathway in RAW264.7 macrophages and in COPD mice

“…Mechanistic studies show that silent information regulator 1 (SIRT1) is involved in the pathogenesis of COPD, with decreased levels in bronchial epithelial cells (Beas-2B) and mouse lungs exposed to cigarette smoke extract (CSE), as well as in the lungs and blood cells of COPD patients. 9 , 10 SIRT1 belongs to the class III histone/protein deacetylases, which possess anti-inflammatory, anti-aging/senescence properties. 9 , 11 SIRT1-mediated protection in response to CSE-induced lung inflammatory response and injury is linked to the activation of nuclear factor-κB (NF-κB)/p65.…”

Controversial Impact of Sirtuins in Chronic Non-Transmissible Diseases and Rehabilitation Medicine

“…Endothelial progenitor cells (EPCs) have been studied in COPD patients' blood. Also here, downregulation of some genes such as Sirt1 mRNAs, CD31, CD34, and miR-126-3p emerged clearly, while the overexpression of miR-34a was observed only in comparison with signals from healthy smokers [92]. Remarkably, Sirt1 protein and its fragments has been found in COPD serum [93].…”

“…Specifically, Sirt1 120KDa (S120) has been found fragmented in COPD patients compared with healthy smokers or non-smokers subjects [93]. All of these observations suggest the possibility to use CD31, CD34, Sirt1 mRNAs, miR-126-3p, miR-34a [92] and S120 [93] as biomarkers for a better detailed diagnosis of COPD.…”