Implementation of programmed cell death in circulating neutrophils and its special characteristics in experimentally induced hyperhomocysteinemia in a setting of thyroid dysfunction

Abstract

Cardiovascular (CV) disease continues to be the main cause of morbidity and mortality in worldwide. Hyperhomocysteinemia (HHCy) is a novel metabolic risk factor of vascular damage. In addition to that, there is evidence that HHCy management with folic acid and vitamin B supplements prevents atherosclerosis and its sequelae. Oxidative stress is one of the mechanisms behind the cardiotoxic effects of high homocysteine levels. On the one hand, HHCy facilitates endothelial dysfunction, probably as a result of impaired synthesis and/or inactivation of nitrogen (II) oxide (NO). On the other hand, oxidation of homocysteine is accompanied by formation of reactive oxygen species (ROS), which induce lipid peroxidation in cell membranes and in low density lipoproteins, mitochondrial membrane, secretion of cytochrome C and activation of caspase-3, culminating in apoptosis. Thyroid hormones are known to have a profound effect on CV functions. Hyperthyroidism causes heart rate, myocardial contractility and ejection fraction to increase; this may result in systolic hypertension, systolic heart murmurs, increased left ventricular weight and development of angina and atrial fibrillation with a risk for stroke.