MYOCARDIAL OSTEOPONTIN EXPRESSION IS ASSOCIATED WITH LEFT-VENTRICULARHYPERTROPHY

Background Osteopontin (OP) has been identified in cultured rat cardia c fibroblasts, where it contributes to angiotensin II (AII)-induced re modeling processes; in cultured cardiomyocytes; and in macrophages in cardiac tissues with inflammation. However, the presence of OP has not been reported in histological sections of myocardial tissue. In the p resent study, we investigated (1) the regulation of OP mRNA expression in cultured rat cardiomyocytes; (2) the localization of OP mRNA in ne onatal and adult normal and hypertrophied rat hearts; and (3) the hist ology of OP expression in myocardial specimens from humans either with myocyte hypertrophy or with no pathological changes. Methods and Resu lts Cultured neonatal cardiomyocytes expressed OP mRNA and were immuno reactive for OP. Endothelin-1 (ET-1) and norepinephrine (NE) increased both OP and atrial natriuretic peptide (ANP) mRNA levels twofold to t hreefold (P<.01). OP mRNA was prominent in ventricular tissue from neo natal and adult rats with renovascular hyper tension and aortic bandin g, whereas barely detectable levels were observed in normal adult card iac tissue. ANP and OP mRNA levels in normal and hypertrophied ventric les correlated (r(2)=.87, P<.001). OP immunoreactivity and mRNA transc ripts were predominantly found in cardiomyocytes not associated with i nflammatory cells in sections from neonatal and adult hypertrophied he arts. No staining was delectable in normal adult hearts. Human myocard ium with extensive fibrosis and cardiomyocyte hypertrophy obtained fro m explanted hearts with either idiopathic (n=5) or ischemic cardiomyop athy (n=7) demonstrated substantial myocyte immunoreactivity for both OP and ANP in right and left ventricles that was not associated with l eukocyte infiltration. In situ hybridization identified cardiomyocytes as the major source of OP mRNA transcripts in these hearts. In contra st, OP immunoreactivity was not detectable in four of five endomyocard ial biopsies with normal histology. Conclusions The present study prov ides the first evidence that cardiomyocytes are a prominent source of OP in vivo and suggests that induction of OP expression is strongly as sociated with ventricular hypertrophy.