Differential expression of osteopontin, and osteoprotegerin mRNA in epicardial adipose tissue between patients with severe coronary artery disease and aortic valvular stenosis: association with HDL subclasses

Abstract

BackgroundPrevious studies suggest a relationship of the epicardial adipose tissue (EAT) with progression and calcification of the atherosclerotic plaque; however, it is unknown if this tissue expresses genes that may participate on these processes and if the expression of these genes is regulated by high-density lipoprotein (HDL) subclasses.MethodsTo explore this possibility, we determined the mRNA expression by qPCR of a pro-calcifying gene (osteopontin (OPN)), and two anti-calcifying genes (osteoprotegerin (OPG) and osteonectin (ON)), in biopsies of EAT obtained from 15 patients with coronary artery disease (CAD) determined by angiography, and 15 patients with diagnostic of aortic valve stenosis but without CAD as control group. We determined the distribution and composition of HDL subclasses by electrophoresis and their statistical relationship with the gene expression in EAT.ResultsEAT from CAD patients showed a higher expression level of OPN and OPG than control group, whereas ON expression was similar between groups. Large HDL subclasses were cholesterol-poor in CAD patients as estimated by the cholesterol-to-phospholipid ratio. A linear regression model showed an independent association of OPN expression with HDL3a-cholesterol, and OPG expression with the relative proportion of HDL3b protein. Logistic analysis determined that OPN expression was positively associated with the presence of atherosclerotic plaqueConclusion OPN, ON, and OPG genes are transcribed in EAT; to the exception of ON, the level of expression was different in CAD patients and control group, and correlated with some HDL subclasses, suggesting a new role of these lipoproteins.Electronic supplementary materialThe online version of this article (doi:10.1186/s12944-017-0550-2) contains supplementary material, which is available to authorized users.

<p>Bone Morphogenetic Protein-2 and Osteopontin Gene Expression in Epicardial Adipose Tissue from Patients with Coronary Artery Disease Is Associated with the Presence of Calcified Atherosclerotic Plaques</p>

“…We have previously demonstrated that EAT expresses genes related with coronary calcification such as osteopontin (OPN), osteonectin (ON), and osteoprotegerin (OPG), 11 thus suggesting that EAT directly participates on coronary calcification. However, it remains unknown whether the pro-calcifying factors expressed by EAT are associated with the amount of calcium deposited in the coronary arteries.…”

“…However, it remains unknown whether the pro-calcifying factors expressed by EAT are associated with the amount of calcium deposited in the coronary arteries. Since the coronary artery calcification (CAC) score was not determined in that exploratory study, 11 we recruited new groups of patients and controls in order to look for a potential biological impact of such mRNA expressions on coronary calcification. We quantified the CAC score and the EAT volume by tomography, as well as the gene expression in EAT from patients with coronary artery disease (CAD), including OPN, ON, OPG, and bone morphogenetic protein (BMP)-2 and BMP-4.…”

Elevated Circulating Osteoprotegerin Levels in the Plasma of Hemodialyzed Patients With Severe Artery Calcification

“…On the other hand, osteopontin (OPN) it is a multi‐functional protein that promotes the inflammatory micro‐environment characteristic of the atherosclerosis. OPN increases with progression and calcification of the atherosclerotic plaque, suggesting a pro‐calcifying role of this protein .…”

Osteopontin: The Molecular Bridge between Fat and Cardiac–Renal Disorders

“…Indeed, ATMs are the primary source of pro-inflammatory mediators inside the adipose tissue and directly implicated in the pathogenesis of obesity-associated disorders, including cardiac and renal diseases [59][60][61][62]. In the last years, the CLs have become synonymous with metabolic dysfunction, perhaps for the rate of adipocyte death in obesity causing inflammation [58,63,64]. Intriguingly, it is demonstrated that OPN is expressed predominantly by ATMs in adipose tissue and regulates the local inflammation and cell death [60].…”

“…For this reason, it is highlighted that VAT is the main source of OPN during obesity [65]. In addition, the metabolic changes orchestrated by OPN in VAT [66,67] advance the hypothesis of its role as a key regulator of the inflammatory processes of obesity-induced adipose tissue inflammation [64] and become a possible target for treatment of adipose tissue-associated disorders, such as cardiac and renal diseases [15,17].…”