6533b86efe1ef96bd12cca72

RESEARCH PRODUCT

Genetic variants of ANP and cardiometabolic protection: from populations to novel therapeutics

subject

description

Background The cardiac hormone atrial natriuretic peptide (ANP) induces natriuresis, vasodilation and inhibits aldosterone through the activation of the guanylyl cyclase A receptor (GC-A) and the second messenger cGMP. ANP possesses also metabolic properties enhancing lipolysis and release of the adipokine adiponectin. Previous studies in general populations reported that the minor G allele of the ANP genetic variant rs5068 is associated with increased circulating levels of ANP and B-type natriuretic peptide, lower blood pressure (BP), and reduced risk of hypertension. We recently reported that in the general population from Olmsted County, MN, USA the G allele of rs5068 is associated not only with increased levels of ANP and lower BP but also with lower BMI, prevalence of obesity and metabolic syndrome. To advance our understanding of the phenotype associated with rs5068 we analyzed a community-based cohort from Sicily, Italy. Our second aim was to advance a potential therapeutics for cardiometabolic disease employing a novel long-acting ANP, MANP whose biological actions were defined in canines and in a rat model of metabolic syndrome.