CATESTATIN (CST) AND ITS VARIANTS FOR TREATMENT OF CARDIOVASCULAR AND METABOLIC DISORDERS

摘要

Circulating levels of catestatin (Cts: human chromogranin A352-372) decrease in the plasma of patients with essential hypertension. Genetic ablation of the chromogranin A (Chga) gene in mice increases blood pressure and pre-treatment of Chga-null mice with Cts prevents blood pressure elevation, indicating a direct role of Cts in preventing hypertension. This notable vasoreactivity prompted us to test the direct cardiovascular effects and mechanisms of action of wild-type Cts (WT-Cts) and naturally occurring human variants (G364S-Cts and P370L-Cts) on myocardial and coronary functions. The cardio-inhibitory influence exerted on basal mechanical performance and the counter-regulatory action against beta-adrenergic and ET-1 stimulations, point to Cts as a novel cardiac modulator, able to protect the heart against excessive sympathochromaffin over-activation, e.g. hypertensive cardiomyopathy.