C-type natriuretisch peptide beschermt vasculaire en cardiale functie bij sepsis

BACKGROUND:Sepsis is a life-threatening condition and a major cause of mortality in intensive care units worldwide, a clear unmet medical need. CNP (C-type natriuretic peptide) regulates inflammation and cardiovascular homeostasis, but its involvement in sepsis pathogenesis is not fully elucidated. This study investigated the intrinsic role of CNP, and therapeutic potential of the peptide, in offsetting the pathogenesis of sepsis.METHODS:Plasma concentrations of CNP, and its N-terminal cleavage product NT-proCNP (N-terminal pro-CNP), were measured in sepsis patients. Cardiac function, vascular hemodynamics, endothelial integrity, and biomarkers of inflammation were analyzed in wild-type, endothelium-restricted (ecCNP−/−), or cardiomyocyte-restricted (cmCNP−/−) CNP knockout animals, or global NPR (natriuretic peptide receptor)-C−/−deficient mice, in etiologically distinct models of sepsis. CNP (0.2 mg/kg per d) was infused to rescue any adverse phenotype and probe therapeutic potential.