Expression of Heme Oxygenase-1 in Response to Myocardial Infarction in Rats

P. Lakkisto, E. Palojoki, T. Bäcklund, A. Saraste, I. Tikkanen, L.-M. Voipio-Pulkki and K. Pulkki. Expression of Heme Oxygenase-1 in Response to Myocardial Infarction in Rats. Journal of Molecular and Cellular Cardiology (2002) 34, 1357–1365. Heme oxygenase-1 (HO-1) is a heat shock protein catalysing the degradation of heme to yield biliverdin, carbon monoxide and iron. Several recent studies have proposed the stress-inducible HO-1 to participate in cellular protection also in the heart. We, therefore, examined the expression and localization of HO-1 in a rat experimental myocardial infarction model. Male Wistar rats were subjected to left anterior coronary artery ligation or sham-operation and sacrificed at 1 day, 1 week and 4 weeks after ligation. The expression of HO-1 mRNA was assessed by real-time quantitative RT-PCR and the localization of HO-1 protein by immunoconfocal microscopy. At day 1, HO-1 mRNA was increased 3.9-fold in the peri-infarct border area vs sham-operated hearts (P<0.001) and 2.9-fold vs remote areas of the same hearts (P<0.001). At 1 week, HO-1 mRNA levels remained significantly higher (5-fold) in the peri-infarct border area than in sham-operated hearts (P<0.001). In addition, HO-1 mRNA transiently increased 1.6-fold in the remote non-infarcted myocardium vs sham operated hearts (P<0.05). HO-1 mRNA returned to basal levels by 4 weeks. The increase in HO-1 mRNA was accompanied by increased immunoreactivity of HO-1 protein in the vascular walls throughout the myocardium, and in the cardiomyocytes and fibroblast-like cells of the peri-infarct border areas. Cardiomyocytes showed immunoreactivity at the intercalated disc area, and in the sarcoplasmic reticulum as indicated by the striated pattern of staining. The results suggest that the induction of HO-1 may have an important role in the heart during the first days after myocardial infarction.