Assessment of mitochondrial respiratory capacity in relation to cardiac contractile performance in patients with normal to mildly decreased cardiac systolic function.

Chronic heart failure (CHF) with reduced left ventricular ejection fraction (LVEF) is associated with remodeling of cardiac energy metabolism; however, experimental data from human hearts that are still in early stages of contractile decline are very sparse. In the current study, we probed the association between LV contractility and myocardial capacity for fatty acid and carbohydrate oxidation in patients having normal-to-mildly decreased systolic function. In patients undergoing coronary artery bypass grafting surgery (n=40, EF ≥40%), a sample of left ventricular myocardium was obtained by subepicardial needle biopsy. Mitochondrial respiratory capacity, as well as oxidation of individual fatty acid and carbohydrate substrates (palmitoyl-carnitine and pyruvate, respectively), were assessed by measuring the rate of oxygen consumption. Also, expression of key mitochondrial metabolic factors and tissue accumulation of ceramide were evaluated, and correlation analysis was performed. Maximal mitochondrial respiration, and expression of mitochondrial biogenesis and remodeling factors (PGC-1α and mitofusin-2) were positively correlated with LVEF (r=0.37-0.50; P<0.05). Although there was no relationship between LVEF and respiration driven by individual metabolic substrates, LVEF was positively correlated with expression of key ß-oxidation enzymes. Finally, LVEF was inversely correlated with accumulation of cardiotoxic ceramide (r=0.89, P<0.05). In patients with coronary artery disease exhibiting normal-to-mildly decreased LVEF, cardiac systolic function is associated with mitochondrial respiratory capacity and levels of fatty acid oxidation enzymes, pointing to them as factors involved in early phases of myocardial pathological remodeling.

Association of anticardiolipin antibodies, complement and leptin with the severity of coronary artery disease expressed as syntax score.

Chronic inflammation plays a role in all stages of atherosclerosis leading to coronary artery disease (CAD), with elevated inflammatory markers being associated with the worse clinical outcome. The goal of the current study was to examine possible association between pro-inflammatory/pro-coagulant factors; anticardiolipin (aCL) autoantibodies, complement C3, C4 and leptin, and the severity of CAD expressed as SYNTAX score. Patients with symptoms of cardiac ischemia undergoing coronary angiography were recruited, and their blood levels of aCL-IgG, aCL-IgM, complement C3, C4 and leptin were assessed. Their association with the SYNTAX score, calculated based on coronary angiography findings, was analyzed. All patients had aCL antibody titer within the normal range. A significant positive association was found for aCL-IgG and SYNTAX score. Male patients had higher average aCL-IgG concentration and SYNTAX score than female patients. No association was found between SYNTAX score and C3 and C4. On the other hand, leptin was negatively associated with SYNTAX score. Our study demonstrates an association between the extent of CAD and aCL-IgG even in the absence of systemic autoimmune disease and at the aCL-IgG levels that are within the normal range. Also, association of lower leptin levels with more severe CAD suggests that its pro-inflammatory effects might not contribute to the pathogenesis of CAD, and that leptin might even exert protective effects on coronary vasculature.