A Central Role of Heme Oxygenase-1 in Cardiovascular Protection

Abstract

The intrinsic defense mechanisms of the body are critical in protecting tissues from injury in response to pathological stress. Heme oxygenase-1 (HO-1), a stress response protein, is induced in response to various pathological stimuli to serve a cytoprotective function. By degrading the oxidant heme and generating the antioxidant bilirubin and anti-inflammatory molecule carbon monoxide, HO-1 may protect cell from injury due to oxidative and pathological stress. Oxidative stress in the heart caused by ischemia and reperfusion leads to cardiomyocyte death and subsequent myocardial infarction. Vascular diseases including atherosclerosis, graft failure, and restenosis are all associated with reactive oxygen species-induced injury and inflammation. Given that cardiovascular disease is the leading cause of death worldwide, there is considerable interest in developing new strategies for preventing and treating cardiovascular disease. Since HO-1 is induced in the heart and blood vessels in response to various stresses, a role of HO-1 has been implicated in cardiovascular homeostasis. Numerous studies using pharmacological method or genetic approach have since demonstrated the cardiovascular protective function of HO-1. Importantly, a number of studies have associated human HO-1 gene promoter polymorphisms with risk for vascular diseases. Taken together, HO-1 has a great therapeutic potential for cardiovascular disease.

The Mononuclear Phagocyte System in Homeostasis and Disease: A Role for Heme Oxygenase-1

“…The byproducts of HO-1 enzymatic activity are cytoprotective because of their antioxidant and antiinflammatory properties (83,122,130). The well-established ability of HO-1 expression to prevent injury in a number of disease models has been extensively reviewed elsewhere (13,127,130,141,159,186). This review presents current evidence and concepts on the involvement of HO-1 and heme on mononuclear phagocytes (MP) with a particular emphasis on macrophages and dendritic cells (DC).…”

Possible Role of Nrf2 in Oxidative and Inflammatory Processes During Menopause

“…The atheroprotective effect of HO-1 may be associated with the partial deletion MMP9 to maintain or improve the stability of the plate, avoiding a coronary event or acute and potentially fatal brain [48,49].…”

Gene Therapy of the Heart through Targeting Non-Cardiac Cells

“…HMOX-1 is an inducible member of the heme oxygenase family of proteins, also consisting of the constitutive heme oxygenase-2 and the less well characterized heme oxygenase-3 (Durante et al, 2010, Wu et al, 2010. HMOX-1 expression is induced by its substrates: heme, oxidants, heavy metals, cytokines, growth factors, hemodynamic forces, gases, hypoxia, and hormones (Wu et al, 2011). Many transcription factors may be involved in its regulation.…”

“…Many transcription factors may be involved in its regulation. Some of them are HIF-1 , nuclear factor kappa B, activator protein 1, and nuclear factor E2-related factor (Wu et al, 2011). HMOX-1 catalyzes the degradation of heme into biliverdin, free iron, and carbon monoxide (Maines et al, 1986).…”