Renin expression at sites of repair in the infarcted rat heart

Angiotensin (Ang) II has autocrine and paracrine Functions that contribute to structural cardiac remodeling by fibrous tissue following myocardial inf arction (MI). The recruitment of angiotensin converting enzyme (ACE) and An gII receptors by inflammatory and fibroblast-like cells involved in tissue repair of the infarcted heart is now well established. On the other hand. t he temporal and spatial response and cellular source of renin in infarcted hearts have not been Fully elucidated, The relationship between renin synth esis and circulating renin activity have likewise not been addressed. The p resent study sought to assess the cellular source, spatial distribution and temporal response of renin expression and synthesis in the rat heart follo wing anterior transmural MI. and to determine its relationship to circulati ng renin activity. At day 3 and weeks 1, 2, 3 and 4 following left coronary artery ligation, the localization and optical density of cardiac renin mRN A was detected by quantitative in situ hybridization: cardiac and circulati ng renin activity was measured by radioimmunoassay: cells expressing cardia c renin were detected by immunohistochemistry: and injury/repair was assess ed by hematoxylin/eosin and collagen-specific picrosirius red staining, Uno perated rats served as normal controls. The authors found: (1) renin mRNA a nd activity were not detected in either normal control or non-infarcted myo cardium, but were expressed at the site of infarction and other sites of re pair involving visceral pericardium and endocardium of interventricular sep tum at all lime points: (2) cells expressing renin at day 3 and weeks 1 and were predominantly macrophages, while at weeks 3 and 4. they were primaril y myofibroblasts; (3) renin activity in the infarcted myocardium rose progr essively over the course of 4 weeks: and (4) circulating renin activity M a s significantly increased at day 3 and week 1, reached a peak at week 2. de clined at week 3 and returned to normal levels at week 4. Thus, renin expre ssion and activity appear at sites of repair in the infarcted rat heart on day 3 and rise progressively thereafter over 4 weeks, independent of circul ating renin. Several types of cells are responsible for renin synthesis at these sites: primarily macrophages during the inflammatory phase of repair, and myofibroblasts during the subsequent fibrogenic phase. Cardiac renin p roduction Following MI contributes to local AngII generation that regulates tissue repair and structural remodeling following MI. (C) 2001 Academic Pr ess.