Abstract
BackgroundLipid dysregulation is a classical risk factor for cardiovascular disease (CVD), yet scanty evidence existed regarding cardiac lipid metabolism that is directly related to heart damage. Recently, the relationship between dyslipidemia and pro-inflammatory insults has led to further understanding on the CVD-predisposing effects of dyslipidemia. The aims of the present study were to investigate whether high-fat high-cholesterol (HFHC) diet-induced hyperlipidemia would cause heart damage and to study the potential role of local cardiac lipid dysregulation in the occurrence of cellular injury.MethodsMale Sprague–Dawley rats were divided into normal chow or HFHC diet groups, and sacrificed after 2 or 4 weeks, respectively. Lipid peroxidation marker level was measured. Lipid parameters in the rat hearts were detected. Cardiac damage was evaluated.ResultsHFHC diet increased serum levels of cholesterol and free fatty acids (FFAs) and led to systemic oxidative stress and pro-inflammatory status. Cardiac lipid dysregulation, which was characterized by elevated levels of cholesterol and adipocyte (A)- and heart (H)-fatty acid binding proteins (FABPs), occurred after HFHC diet for 4 weeks. Cardiac damage was further evident with elevated circulating H-FABP levels, increased cardiac interstitial fibrosis and the loss of troponin I.ConclusionOur data demonstrated that HFHC diet led to systemic and cardiac lipid dysregulation, accompanied by systemic oxidative and pro-inflammatory stresses, and these may finally cooperate to cause a series of pathological changes of the heart tissue. Our findings suggest that maintenance of lipid regulation may be essential in the prevention of heart damage.
Highlights
Lipid dysregulation is a classical risk factor for cardiovascular disease (CVD), yet scanty evidence existed regarding cardiac lipid metabolism that is directly related to heart damage
Cells are prevented from intracellular cholesterol accumulation through precise regulation of synthesis, influx and efflux of cholesterol. 3-Hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase is a key enzyme regulating and limiting the rate of synthesis; cholesterol influx is mediated by low-density lipoprotein (LDL) receptor and efflux is mainly controlled by ATP-binding cassette transporter A1 (ABCA1) [4, 5]
high-fat high-cholesterol (HFHC) diet resulted in significant increases in serum total cholesterol reflected by suppressed high-density lipoprotein (HDL)-C levels and elevated LDL-C levels and in serum free fatty acids (FFAs) levels
Summary
Lipid dysregulation is a classical risk factor for cardiovascular disease (CVD), yet scanty evidence existed regarding cardiac lipid metabolism that is directly related to heart damage. 3-Hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase is a key enzyme regulating and limiting the rate of synthesis; cholesterol influx is mediated by LDL receptor and efflux is mainly controlled by ATP-binding cassette transporter A1 (ABCA1) [4, 5]. Factors that compromise these mechanisms may lead to excess accumulation of cholesterol, which may in turn lead to cytotoxicity characterized by enhanced necrosis and apoptosis of cells [6]
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