Joint analysis of left ventricular expression and circulating plasma levels of Omentin after myocardial ischemia

Louis A Saddic,Simon C Body,Joshua Gorham,Sarah M Nicoloro,Sary F Aranki,Stanton K Shernan,Olga T Gupta,Christine E Seidman,Timothy P Fitzgibbons,Michael P Czech,Jochen D Muehlschlegel,Jon G Seidman

doi:10.1186/s12933-017-0567-x

Abstract

BackgroundOmentin-1, also known as Intelectin-1 (ITLN1), is an adipokine with plasma levels associated with diabetes, obesity, and coronary artery disease. Recent studies suggest that ITLN1 can mitigate myocardial ischemic injury but the expression of ITLN1 in the heart itself has not been well characterized. The purpose of this study is to discern the relationship between the expression pattern of ITLN1 RNA in the human heart and the level of circulating ITLN1 protein in plasma from the same patients following myocardial ischemia.MethodsA large cohort of patients (n = 140) undergoing elective cardiac surgery for aortic valve replacement were enrolled in this study. Plasma and left ventricular biopsy samples were taken at the beginning of cardiopulmonary bypass and after an average of 82 min of ischemic cross clamp time. The localization of ITLN1 in epicardial adipose tissue (EAT) was also further characterized with immunoassays and cell fate transition studies.ResultsmRNA expression of ITLN1 decreases in left ventricular tissue after acute ischemia in human patients (mean difference 280.48, p = 0.001) whereas plasma protein levels of ITLN1 increase (mean difference 5.24, p < 0.001). Immunohistochemistry localized ITLN1 to the mesothelium or visceral pericardium of EAT. Epithelial to mesenchymal transition in mesothelial cells leads to a downregulation of ITLN1 expression.ConclusionsMyocardial injury leads to a decrease in ITLN1 expression in the heart and a corresponding increase in plasma levels. These changes may in part be due to an epithelial to mesenchymal transition of the cells that express ITLN1 following ischemia.Trial Registration Clinicaltrials.gov ID: NCT00985049

Highlights

Adipose tissue is a complex organ whose functions extend well beyond its canonical role in energy storage [1,2,3]
Plasma ITLN1 protein levels increase while left ventricular ITLN1 RNA expression decreases following myocardial ischemia in humans We used our prior cardiopulmonary bypass (CPB) model in patients undergoing aortic valve replacement to obtain pre-ischemia and post-ischemia samples [21]
We show that pre-ischemia levels of ITLN1 expression in the human myocardium are much higher than the nominal levels depicted in the GTEX consortium [36]

Summary

Introduction

Adipose tissue is a complex organ whose functions extend well beyond its canonical role in energy storage [1,2,3]. Saddic et al Cardiovasc Diabetol (2017) 16:87 the vast majority of ITLN1 expression from adipose tissue is derived from the stromal vascular compartment with only trace amounts produced in adipocytes [8] This is in contrast to many other adipokines which are primarily expressed in fat cells [7]. A recent study showed that systemic administration of human ITLN1 in mice leads to a reduction in infarct size and myocyte apoptosis after ischemia/reperfusion injury through phosphorylation of AMPK and AKT [17] These protective properties of ITLN1 are further substantiated by other studies which have shown that increasing levels of plasma ITLN1 in humans correlate with higher myocardial index scores [17] and a lower frequency of ischemic EKG changes [18]. The purpose of this study is to discern the relationship between the expression pattern of ITLN1 RNA in the human heart and the level of circulating ITLN1 protein in plasma from the same patients following myocardial ischemia

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