Modulation of the monocyte/macrophage system in heart failure by targeting heme oxygenase-1.

Upon myocardial infarction (MI) immune system becomes activated by extensive necrosis of cardiomyocytes releasing intracellular molecules called damage-associated molecular patterns. Overactive and prolonged immune responses are likely to be responsible for heart failure development and progression in patients surviving the ischemic episode. Heme oxygenase-1 (HO-1) plays a crucial role in heme degradation and in this way releases carbon monoxide, free iron, and biliverdin. This stress-inducible enzyme is induced by various oxidative and inflammatory signals. Consequently, biological actions of HO-1 are not limited to degradation of a toxic heme released from hemoproteins, but also provide an adaptive cellular response against chronic inflammation and oxidative injury. Indeed, the immunomodulatory and anti-inflammatory properties of HO-1 were demonstrated in several experimental studies, as well as in human cases of genetic HO-1 deficiency. HO-1 was shown to suppress the production, myocardial infiltration and inflammatory properties of monocytes and macrophages what resulted in limitation of post-MI cardiac damage. This review specifically addresses the role of HO-1, heme and its degradation products in macrophage biology and post-ischemic cardiac repair. A more complete understanding of these mechanisms is essential to develop new therapeutic approaches.