Adaptive and Mal-Adaptive Signaling in Cells of the Cardiovascular System: Effect of Obesity-Associated Peptides on Human Blood Platelet Activation

Abstract

Non-communicable, chronic diseases are responsible for ~60 % of all deaths in developing and developed countries. Currently, these diseases account for ~75 % of health care spending in Canada. Although a majority of Canadians express the opinion that health care systems should emphasize prevention strategies, and state supporting funding of prevention programs, the reality is that participation rates in prevention programs are low. Indeed, in North America, 1 in 3 adults are obese. Most disturbingly, 1 in 5 girls and boys between the ages of 6 and 19 is obese and has two or more risk factors for heart disease, including high blood pressure, high cholesterol, diabetes, current smoking and physical inactivity. Research has unequivocally linked obesity, the metabolic syndrome, and other components of “modern life”, such as physical inactivity, as factors that increase the burden of chronic disease. The risk of cardiovascular morbidity is significantly augmented by obesity. A number of peptides, including orexins, obestatin, and neuropeptide Y (NPY), play a pivotal role in the regulation of energy expenditure and also affect other systems and cells. Our studies have elucidated some of the mechanisms through which the endothelium and blood platelets integrate these myriad physio-­pathological stimuli and take advantage of the findings to highlight novel potential therapies to promote adaptive endothelial functions and to reduce the chronic disease-­associated mal-adaptive actions of the endothelium.