Stable CAD patients show higher levels of platelet-borne TGF-β1 associated with a superior pro-inflammatory state than the pro-aggregatory status; Evidence highlighting the importance of platelet-derived TGF-β1 in atherosclerosis.

Abstract

Activated platelets are involved in the atherogenic stage of atherosclerosis, while they can also progress it to atherothrombosis which may cause an ischemic state and organ failure. In general, coronary artery disease (CAD) is considered as common and severe clinical consequence of atherosclerosis, manifesting as a chronic inflammatory condition with the release of platelet mediators, among which the importance of platelet-borne TGF-β1 is not yet well understood. Hence, for the first time, this study aimed to examine platelet level of TGF-β1 (latent/mature) in CAD-patients and its association with the expression of platelet pro-inflammatory molecules. Platelet from stable CAD-patients candidate for CABG and healthy controls were subjected to flowcytometry analysis to evaluate P-selectin and CD40L expressions and PAC-1 binding. Platelet-borne and soluble TGF-β1, both mature/active and latent forms were also examined with western blotting. Higher expression levels of P-selectin and CD40L in patients with CAD than in controls were associated with comparable levels of PAC-1 binding in both groups. Platelet TGF-β1 levels were also significantly higher in patients, while their platelets showed clear bands of mature TGF-β1 that were barely visible in healthy individuals. Soluble TGF-β1 was also higher in patients. Significant correlations between mature/active TGF-β1 and platelet pro-inflammatory markers (P-selectin and CD40L) as well as common indicators of inflammation (CRP and ESR) were observed in CAD patients. In this study, given the insignificant changes in pro-aggregatory potentials in stable CAD, the pro-inflammatory state of platelets may be more involved in disease development and progression. Direct correlations between active platelet-borne TGF-β1 and pro-inflammatory markers with its presence in CAD-patients, which was almost absent in the platelets of healthy individuals, may also underscore the significant contribution of platelet-borne TGF-β1 to the pathogenesis of the disease.