Chapter 6 NOX 5 expression is increased in intramyocardial blood vessels and cardiomyocytes after acute myocardial infarction in humans

Reactive oxygen species (ros)-producing nadph oxidases have been shown to play an important role under different (patho)physiological conditions. Especially nox1, nox2 and nox4 have been proven as important sources of ros in the heart. Knowledge of the calcium-dependent nox5 in the heart is lacking. The presence of nox5 was studied via rt-pcr in heart tissue from end-stage heart failure patients, obtained during cardiac transplantation surgery. In addition, nox5 positivity and cellular localization was studied via immunohistochemistry and digital-imaging microscopy in heart tissue of patients who did not suffer from heart disease, and in infarction areas of patients who died of myocardial infarction of different duration. Furthermore, nox5 was analyzed in isolated human cardiomyocytes via Western blot analysis. nox5 rna was found in the human heart of controls and ischemic cardiomyopathy patients. In control hearts nox5 localized in the endothelium of a limited number of intramyocardial blood vessels and in a limited number of scattered cardiomyocytes. In infarcted hearts, nox5 expression increased especially in infarctions older than twelve hours. This manifested itself as an increase in nox5-positive intramyocardial blood vessels, wherein nox5 was present in endothelium and smooth muscle, but also in cardiomyocytes. In cardiomyocytes nox5 was found in the cytoplasm, plasma membrane, intercalated discs and cross striations. Western blot analysis confirmed nox5 expression in isolated human cardiomyocytes. This study for the first time demonstrates nox5 expression in intramyocardial blood vessels and cardiomyocytes of the human heart, which increased significantly in the affected myocardium after ami.