Protective effect of apolipoprotein AI mimetic peptide 4F on renal and cardiac injury and endothelial dysfunction induced by acute myocardial infarction in hypercholesterolemic rats receiving iodinated contrast

The use of contrast after angiography in infarcted animals induces acute kidney injury, being associated with worsening prognosis and increased mortality. Hypercholesterolemia is an aggravating factor of endothelial injury in acute myocardial infarction (AMI) and the use of contrast in diagnosis and treatment can cause acute kidney injury. Treatment with the apolipoprotein AI mimetic peptide 4F can reverse endothelial injury by reducing LDL levels and preventing its oxidation. OBJECTIVES: To analyze the effect of Apo A-I (using mimetic peptide 4F) on cardiac and renal injury induced by acute myocardial infarction (AMI) with contrast therapy in hypercholesterolemic rats. METHODS: This was a prospective study with rats on a diet at 4% cholesterol for 8 days, divided into a SHAM group operated without coronary ligation (n=6) or infarcted animals with ligation of the left anterior descending coronary artery, with or without the use of contrast and treatment 6 hours after infarction induction: AMI (n=15), AMI+C (iopamidol 2.9 g/kg body weight, intrafemoral artery injection n=15), AMI+4F (4F, 10mg/kg body weight, peritoneal injection, n=8) and AMI+C+4F (n=8). All results are analyzed after 24 AMI and expressed as mean and standard error. RESULTS: It was observed that the AMI+4F and AMI+C+4F groups showed a better response to cardiac injury and renal injury compared to the AMI and AMI+C groups. There was an improvement in renal function through 12-hour creatinine clearance, increased expression of eNOS, increased VEGF, preservation of mitochondrial morphology, reduction of inflammation with a lower expression of CD68+ (macrophages), decreased positive tunnel cells associated with an increase in apolipoprotein AI (Apo AI) expression in renal tissue. The same happened in cardiac function with decreased plasma troponin, increased expression of eNOS, VEGF, isolectin B4, reduction in inflammation represented by lower TLR4 expression, positive tunnel cells, improved cholesterol profile, preservation of mitochondrial morphology and associated with increased expression of Apo AI in cardiac tissue. Hemodynamics were preserved with improvement in cardiac output, ejection fraction, baroreflex response, left ventricular end-diastolic pressure, and associated with a decrease in the infarct area measured by both echocardiogram and immunohistochemistry. We demonstrate that treatment with apolipoprotein AI can be a therapeutic option in cardiac and renal injury by reversing the inflammatory response through the efflux of HDL-dependent cholesterol.