The effects of cadmium on platelet functionAranya Nontarach
( Ph.D. )
Cadmium is an environmental toxicant and has a toxic effect on kidneys, liver, bone and the cardiovascular system. Cadmium causes adverse effects on the vascular endothelial cells and potentiates the platelet reactivity induced by agonists. Chronic cadmium exposure may be a human risk factor of vascular diseases such as hypertension, atherosclerosis and coronary artery disease. The effects of cadmium on human platelets have not been clearly elucidated. In this study, we aimed to determine the levels of platelet activation markers (soluble P-selectin and CD40L) in plasma of chronic cadmium-exposed subjects who lived in a cadmium contaminated area (Mae Sot District, Tak Province), and the effect of cadmium on platelet activation in vitro. The in vitro experiments were designed to study the effects of cadmium on human platelet activation by measuring the platelet aggregation, ATP release and adhesion to human coronary artery endothelial cells (HCAECs). The levels of soluble P-selectin and CD40L in plasma of cadmium-exposed subjects were significantly higher than the levels of the control subjects. As demonstrated by optical aggregometry, cadmium could potentiate the platelet aggregation induced by adenosine diphosphate (ADP), collagen and thrombin receptor activator peptide 6 (TRAP-6). The 50% effective concentrations of agonist-induced platelet aggregation were reduced in the presence of 15 mM cadmium. Cadmium (15 mM) enhanced the platelet ATP release induced by ADP, collagen and TRAP-6. The platelet adhesion to HCAECs, which was induced by ADP, TRAP-6 and thrombin, increased in the presence of 15 mM cadmium. Pre-treatment of platelets with N-acetylcysteine could attenuate the potentiating effects of cadmium on platelet aggregation. In conclusion, chronic cadmium exposure could result in the increase of platelet reactivity. The potentiation by cadmium of platelet reactivity may be related to the increased prevalence of vascular diseases in cadmium-contaminating area.