Increased Protein Kinase C Activity and Expression of Ca2+-Sensitive Isoforms in the Failing Human Heart

Background—Increased expression of Ca2+-sensitive protein kinase C (PKC) isoforms may be important markers of heart failure. Our aim was to determine the relative expression of PKC-β1, -β2, and -α in failed and nonfailed myocardium. Methods and Results—Explanted hearts of patients in whom dilated cardiomyopathy or ischemic cardiomyopathy was diagnosed were examined for PKC isoform content by Western blot, immunohistochemistry, enzymatic activity, and in situ hybridization and compared with nonfailed left ventricle. Quantitative immunoblotting revealed significant increases of >40% in PKC-β1 (P<0.05) and -β2 (P<0.04) membrane expression in failed hearts compared with nonfailed; PKC-α expression was significantly elevated by 70% in membrane fractions (P<0.03). PKC-e expression was not significantly changed. In failed left ventricle, PKC-β1 and -β2 immunostaining was intense throughout myocytes, compared with slight, scattered staining in nonfailed myocytes. PKC-α immunostaining was also more evident in card...