Abstract 746: The Effect of Aging-related Metabolic Disorder on Resistin Expression and Valvular Heart Disorder

Calcific aortic valve stenosis (AS) is the most prevalent valvular heart disease and the third most frequent cardiovascular disease after coronary artery disease and hypertension. AS is characterized by a period of asymptomatic progressive valve calcification, which eventually leads to the development of a severe stenosis and to the onset of symptoms. Visceral obesity is a strong predictor of type-2 diabetes and is associated with insulin resistance. In addition, increased visceral adiposity leads to an increase in systemic release in resistin (Retn) and possibly interleukins. Elevation of circulating adipokines such as Retn plays a role in the development of muscle insulin resistance. Moreover, higher Retn levels were associated with increased valvular inflammation and calcification in the elderly patients, whereas this association was not observed among middle-aged patients. In the current study, we explored the potential role of Retn in ectopic valvular calcification. Analyses of scanning electron microscopy micrographs of calcified aortic valve showed that Retn is more abundant next to calcified nodes. These data corroborate with increased levels of circulating Retn in apoE mice that were fed a high fat high sucrose diet for 24 weeks. Moreover, apoE-/-Retn-/- double KO mutant mice have lower plasma cholesterol level compared to apoE KO mice. In addition, knocking down Retn decreased valve lipid infiltration, lowered glycaemia, calcium nodes and reduced fibrosis. In conclusion, Retn may be a new pharmacological target to stop the progression of aortic stenosis in patients with visceral obesity.