Increased expression of plasma membrane Ca2+ATPase 4b in platelets from hypertensives: A new sign of abnormal thrombopoiesis?

Abstract

Platelet Ca2+ homeostasis is controlled by a multi-Ca2+ATPase system including two PMCA (plasma membrane Ca2+ATPase) and seven SERCA (sarco/endoplasmic reticulum Ca2+ATPase) isoforms. Previous studies have shown similar platelet Ca2+ abnormalities in diabetic and hypertensive patients, including an increase in intracellular [Ca2+]I, a possible modulation of PMCA activity and increased PMCA tyrosine phosphorylation. Very recently, we found that platelets from diabetic patients also exhibited increased PMCA4b expression. In the present study we looked for further similarities between diabetic and hypertensive patients. We first confirmed a decrease in Ca2+ATPase activity (mean 55 + 7%) in mixed platelet membranes isolated from 10 patients with hypertension compared with those from 10 healthy controls. In addition, the decreased Ca2+ATPase activity correlated with the DBP of the different patients, as expected for PMCA activity. Second, we performed a pilot study of six hypertensives to examine their expressions of PMCA and SERCA mRNA and proteins. Like the diabetic patients, 100% of hypertensives were found to present a major increase in PMCA4b expression (mean value of 218 ± 21%). We thus determined that platelets from diabetic and hypertensive patients showed similar increased PMCA4b isoform. Since increased PMCA4b expression was recently found to be associated with a perturbation of megakaryocytopoiesis, these findings may also point to an abnormality in platelet maturation in hypertension.