Effect of angiotensin-converting enzyme inhibitors, captopril and lisinopril, on collagen synthesis by cultured rat liver cells

ABSTRACT

Several studies have documented the role of angiotensin-converting enzyme inhibitors [ACEI] as antifibrogenic and antiproliferative in different tissues in vivo and in vitro but unfortunately non of them has investigated this effect on collagen synthesis by individual liver cells. In this study we focused on the in vitro effect of two ACEI with different pharmacologic properties, captopril and lisinopril, on the synthesis of types I and III collagens by individual liver cells, since these types of collagens are the most abundant ECM molecules both in normal and fibrotic liver. Rat liver cells were isolated, separated according to cell types through density gradient centrifugation in percoll then cultured as separate clones for 24 hours. Types I and III collagens secretion was measured by gel electrophoresis [SDS-PAGE] and computer analysis of their alpha chains after purification from cell culture media. Both captopril and lisinopril significantly reduced types I and III collagens by cultured hepatocytes [HC], liver endothelial cells [EC], and hepatic stellate cells [HSC] with more prominent action for captopril than lisinopril. The present study document the inhibitory effect of ACEI on types I and III collagen synthesis by liver cell sub-population in vitro by a mechanism independent on the systemic angiotensin-converting enzyme inhibition and possibly through a mechanism involving a local renin-angiotensin system or interference with intracellular events involved in collagen synthesis: