Atrial (ANP) and brain natriuretic peptide (BNP) expression after myocardial infarction in sheep: ANP is synthesized by fibroblasts infiltrating the infarct

Cardiac gene expression of atrial natriuretic peptide (ANP) and that of bra in natriuretic peptide (BNP) are markedly elevated after myocardial infarct ion. The cellular distribution and temporal responses of ANP and BNP messen ger RNA (mRNA) expression mere compared by in situ hybridization for 5 week s after left coronary artery ligation in sheep. Ligation resulted in highly reproducible, transmural, left ventricular infarcts. Within the infarct, A NP mRNA appeared from 7 days after ligation, whereas BNP expression was und etectable in the infarct at any time. The cells synthesizing ANP were shown by in situ hybridization and immunocytochemistry to be fibroblasts invadin g the infarct. The appearance of ANP expression coincided with the transiti on of these cells to the myofibroblast phenotype. Treatment of cultured car diac fibroblasts with transforming growth factor-beta (10 ng/ml) induced th e expression of alpha -smooth muscle actin, characteristic of the transform ation to myofibroblasts, and raised ANP concentrations in the medium. In th e surviving myocardium of the left ventricle, ANP and BNP expression increa sed in response to ligation, BNP mRNA was particularly strong at the latera l margins of the infarct. In both left, and right atria, levels of BNP mRNA increased markedly over the first 18 h, whereas levels of atrial ANP mRNA decreased over 3 days after infarction. This is the first report of ANP exp ression and synthesis by cardiac fibroblasts invading the fibrotic scar, su ggesting that ANP may be involved in regulating fibroblast proliferation du ring reparative fibrosis.