Carbon monoxide

A role for HO-1 (also known as HSP 32) in cardiac homeostasis was first implicated in a study showing that HO-1 expression in the heart is increased in response to hyperthermia. The first genetic deficiency of HO-1 in human was reported in a young boy in 1999 and a second case was reported recently in a young girl who both died at early ages: 6 and 15 years old, respectively. Both cases showed severe inflammatory phenotypes including elevated expression of inflammatory markers such as C-reactive protein, ferritin, and von Willebrand factor. They also had coagulopathy, nephritis, chronic inflammation, and increased susceptibility to atherosclerosis. The human HO-1 deficiency reveals a critical immunomodulatory role of HO-1 and highlights the essential function of HO-1 in human health and disease. In addition, an absence of HO-1 exacerbates ischemia/reperfusion-induced myocardial damage. HO-1 transgenic mice reveal that HO-1 overexpression reduces myocardial infarct size and inflammatory cell infiltration following ischemia/reperfusion injury, demonstrating the protective role of HO-1 against myocardial infarction. In this phenomena, postinfarction survival and alleviated postinfarction pathological left ventricular remodeling were improved, through induced neovascularization and ameliorated apoptosis. Adult bone marrow-derived stem cells seem to be a promising therapeutic tool against damaged myocardium, however, the therapy is limited by poor viability of graft cells. Mesenchymal stem cells (MSCs), containing HO-1 vector protects cardiomyocytes from apoptosis after implantation in mouse hearts 1 h after MI. In another gene transfer study, injection of adenoviral-HO-1-transduced MSCs into rat hearts 1 h after myocardial infarction reduced infarct size. Along with these results, decreased cardiac proinflammatory cytokines content but increased anti-inflammatory cytokine IL -10 expression were reported. Interestingly, HO-1-MSC increases TIMP2/3 expression and decreases MMP2/9 expression and thus normalizes the ratio of MMPs/TIMPs in transplanted hearts, suggesting that modulation of the MMPs/TIMPs system might be another mechanism that contributes to cardioprotective effect of HO-1.