ANP (atrial natriuretic peptide), discovered 30 years ago in rat cardiac atria, has been extensively investigated with regard to physiology, pathophysiology, cardiovascular disease therapeutics and molecular genetic aspects. Besides its diuretic, natriuretic and vasorelaxant effects, novel properties of this hormone have been described. Thus anti-hypertrophic, anti-fibrotic, anti-proliferative and anti-inflammatory actions suggest that ANP contributes not only to haemodynamic homoeostasis and adjustments, but has also a role in cardiovascular remodelling. Circulating ANP levels represent a valuable biomarker in cardiovascular diseases. ANP structure is highly conserved among species, indicating a key role in cardiovascular health. Thus an abnormal ANP structure may contribute to an increased risk of disease due to altered functions at either the vascular or cardiac level. Among others, the 2238T>C exon 3 variant has been associated with endothelial cell damage and dysfunction and with an increased risk of acute cardiovascular events, a frameshift mutation within exon 3 has been related to increased risk of atrial fibrillation, and ANP gene variants have been linked to increased risk of hypertension in different ethnic groups. On the other hand, the rs5068 variant, falling within the 3′ UTR and associated with higher circulating ANP levels, has been shown to have a beneficial cardioprotective and metabolic effect. Dissecting out the disease mechanisms dependent on specific ANP molecular variants may reveal information useful in the clinical setting for diagnostic, prognostic and therapeutic purposes. Furthermore, insights from molecular genetic analysis of ANP may well integrate advancing knowledge on the role of ANP as a significant biomarker in patients affected by cardiovascular diseases.

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