Determination of the effects of insulin resistance, atherosclerosis and cardiac hypertrophy on heart failure in mice.

The risk of cardiovascular diseases is directly related to the concomitant burden of the obesity-related metabolic syndrome factors: dyslipidemia, hyperglycemia and insulin resistance, and hypertension. Furthermore, visceral obesity is an independent risk factor for development of type-2 diabetes and heart failure. The mechanisms that link obesity with type-2 diabetes and with cardiovascular risk and heart failure remain to be elucidated. Obesity is increasingly recognized as a low-grade inflammatory and oxidative stress state, associated with enhanced activation and subsequent infiltration of monocytes in adipose and cardiovascular tissues. There they may induce oxidative stress and inflammation, and impair insulin action, lipid metabolism, blood pressure regulation, and vascular and cardiac remodeling. The molecular mechanisms remain to be unraveled. To investigate the underlying mechanisms, we developed relevant mouse models displaying different stages of obesity, dyslipidemia, hyperglycemia and insulin resistance, and hypertension. They also display different stages of atherosclerosis, ventricular hypertrophy and stiffness, and cardiac output. To study the underlying mechanisms, we combine molecular pathway analysis, and therapeutic and gene-specific silencing and overexpression interventions, with metabolic and functional measurements.

Keywords:Cardiovascular diseases, Oxidative stress, Inflammation, Obesity, Heart failure, Atherosclerosis

Disciplines:Cardiac and vascular medicine