Cardioprotective effects of prior transient ACE inhibition ő role of cardiac fibroblast (1152.7)

Abstract

Transient ACE inhibition induces persistent changes that protect against future L‐NAME‐induced cardiac fibrosis and inflammation. This study investigates whether these observations can be mechanistically linked to changes in cardiac fibroblasts.We measured cardiac levels of chemokines, macrophages, and proliferating cells following 7 days of L‐NAME (L) in SHR that were previously treated with placebo (C+L) or enalapril (E+L) for 2wks followed by 2wk washout. Cardiac fibroblasts were isolated and cultured to passage 1.L‐NAME induced microinfarcts and vascular injury in both groups. In C+L, but not E+L there was an increase in macrophage‐recruiting chemokines. By day 7 of L‐NAME there was a marked increase in cardiac macrophages and proliferating cells in C+L, but not E+L. In vitro, fibroblasts from C+L were hyperproliferative, demonstrated increased Collagen I gene expression, and increased MCP‐1 production.These findings demonstrate that L‐NAME produces phenotypic changes in fibroblasts that persist in vitro that suggest that fibroblasts may participate in macrophage recruitment in addition to collagen production. However, fibroblasts isolated from SHR previously treated with enalapril display a different phenotype that more closely resembles cells from control hearts. ACE inhibitor‐induced cardioprotection may result, in part, from a modification of the cardiac fibroblast population.Grant Funding Source: Supported by: Sarver Heart Foundation, Steven M Gootter Foundation