Deficiency of adipocyte fatty-acid-binding protein alleviates myocardial ischaemia/reperfusion injury and diabetes-induced cardiac dysfunction

Abstract

Clinical evidence shows that circulating levels of adipocyte fatty-acid-binding protein (A-FABP) are elevated in patients with diabetes and closely associated with ischaemic heart disease. Patients with diabetes are more susceptible to myocardial ischaemia/reperfusion (MI/R) injury. The experiments in the present study investigated the role of A-FABP in MI/R injury with or without diabetes. Non-diabetic and diabetic (streptozotocin-induced) A-FABP knockout and wild-type mice were subjected to MI/R or sham intervention. After MI/R, A-FABP knockout mice exhibited reductions in myocardial infarct size, apoptotic index, oxidative and nitrative stress, and inflammation. These reductions were accompanied by an improved left ventricular function compared with the relative controls under non-diabetic or diabetic conditions. After diabetes induction, A-FABP knockout mice exhibited a preserved cardiac function compared with that in wild-type mice. Endothelial cells, but not cardiomyocytes, were identified as the most likely source of cardiac A-FABP. Cardiac and circulating A-FABP levels were significantly increased in mice with diabetes or MI/R. Diabetes-induced superoxide anion production was significantly elevated in wild-type mice, but diminished in A-FABP knockout mice, and this elevation contributed to the exaggeration of MI/R-induced cardiac injury. Phosphorylation of endothelial nitric oxide synthase (eNOS) and production of nitric oxide (NO) were enhanced in both diabetic and non-diabetic A-FABP knockout mice after MI/R injury, but diminished in wild-type mice. The beneficial effects of A-FABP deficiency on MI/R injury were abolished by the NOS inhibitor N(G)-nitro-L-arginine methyl ester. Thus, A-FABP deficiency protects mice against MI/R-induced and/or diabetes-induced cardiac injury at least partially through activation of the eNOS/NO pathway and reduction in superoxide anion production.

Knockdown of lncRNA AK139328 alleviates myocardial ischaemia/reperfusion injury in diabetic mice via modulating miR‐204‐3p and inhibiting autophagy

“…The reperfusion therapy with blood flow restoration is the recommended treatment for infarct recovery, yet is more curative for ischaemia of short duration 1, 2. Moreover, reperfusion paradoxically leads to additional damage to ischaemic myocardium 2, 3.…”

Pharmacological inhibition of fatty acid-binding protein 4 (FABP4) protects against renal ischemia-reperfusion injury

“…FABP4 has a well-established role in the development and progression of diabetes and atherosclerosis, [15][16][17]19,20 but the effect of FABP4 in AKI has not been determined. Our study reported for the rst time that overexpression of FABP4 in kidneys, mainly expressed in tubular cells was induced by AKI aer I/R surgery.…”

Role of the fatty acid-binding protein 4 in heart failure and cardiovascular disease

“…Recently, it has been shown that FABP4 is also expressed in cardiomyocytes, and the overexpression of cardiac FABP4 exacerbates the cardiac hypertrophic response induced by pressure overload (Zhang et al 2016). Conversely, FABP4 deficiency attenuates ischaemia-/reperfusioninduced myocardial injury and improves LV function in both non-diabetic and streptozotocin-induced diabetic mice (Zhou et al 2015). Therefore, FABP4 secreted from epicardial fat tissue, subcutaneous and/or visceral adipose tissue or macrophages may influence heart dysfunction in a paracrine or endocrine manner.…”