Effects of menopausal hormone therapy (MHT) on vascular reactive molecules in platelets

Abstract

Activated platelets release mitogenic factors, vascular remodeling enzymes, inflammatory and cellular adhesive molecules into the vascular microenvironment to alter chemotactic and adhesive properties of vascular endothelium. Platelet‐derived growth factor‐BB (PDGF‐BB) and matrix metalloproteinase‐2 (MMP‐2) increased in the platelets following ovariectomy but decreased with estrogen treatment in pigs. Experiments were designed to identify changes in these factors using custom antibody arrays in lysate of platelets collected from women enrolled in the Kronos Early Estrogen Prevention Study (KEEPS) at Mayo Clinic. Washed platelets were prepared from anticoagulated blood before (baseline) and 48 months after randomization into either placebo or oral or transdermal MHT. Preliminary analysis shows after 48 months compared to baseline, platelet content of C‐reactive protein, intercellular adhesion molecule‐1 (ICAM‐1), vascular cell adhesion molecule‐1 (VCAM‐1), PDGF‐BB, MMP‐2 and transforming growth factor‐beta (TGF‐beta) were lower (20–60%) in two groups but higher (20–74%) in one group. Based on our studies in pigs, it is expected that the two groups showing decreases in platelet proteins would be from women randomized to MHT. However, KEEPS will not be unblinded until February 2012. (Supported by grants from Aurora Foundation, NIH HL90639, 1UL1 RR024150).