Abstract
Abstract SCI-34Cardiovascular disease continues to be the major cause of morbidity and mortality in North America and a growing problem in many other parts of the world. The risk of premature atherosclerosis and cardiovascular events rises with increasing obesity and excess adiposity has been linked to increased all-cause mortality. Current estimates show that one in four ischemic heart disease events are attributable to excess weight. Inflammation of adipose tissue orchestrated by monocyte/macrophage infiltration and overproduction of proinflammatory and proatherogenic cytokines may mediate metabolic dysfunction and vascular disease in human obesity. Importantly, obesity has been associated with increased cardiovascular disease as well as enhanced platelet function and thrombosis. We recently measured expression of 48 genes by high-throughput quantitative reverse transcription PCR (qRT-PCR) in over 2250 participants of the Framingham Offspring and Omni minority cohorts (FHS) using RNA from isolated platelets and found that specific inflammatory transcripts including ICAM1, IL1R, IFNG, IL6, COX2, TNF, TLR2, and TLR4 were significantly and positively associated with higher body mass index (BMI) by regression analysis. With the additional measurement of 196 genes, the data has remained extraordinarily consistent. Other cardiovascular risk factors rarely associate with platelet gene expression and BMI remains specifically associated with inflammatory transcripts related to the NFkB-innate immune and inflammatory pathways. These surprising data led to the question: Why would the anucleate platelet have gene expression changes specifically in the setting of increased BMI and can this powerful clinical association be explored using both pre-clinical and clinical studies to find new targets for disease and define new mechanisms for platelet function beyond thrombosis? Disclosures:No relevant conflicts of interest to declare.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have