Heme Oxygenase-1: Clinical Relevance in Ischemic Stroke

Abstract

Stroke is the second-leading cause of death and a leading cause of serious long-term disability worldwide, with an increasing global burden due to the growing and aging population. However, strict eligibility criteria for current treatment opportunities make novel therapeutic approaches desirable. Oxidative stress plays a pivotal role during cerebral ischemia, eventually leading to neuronal injury and cell death. The significant correlation between redox imbalance and ischemic stroke has led to various treatment strategies targeting the endogenous antioxidant system in order to ameliorate the adverse prognosis in patients with cerebral infarction. One of the most extensively investigated cellular defense pathway in this regard is the Nrf2-heme oxygenase-1 (HO-1) axis. In this review, our aim is to focus on the potential clinical relevance of targeting the HO-1 pathway in ischemic stroke.

Keywords: Ischemic stroke; antioxidant system; cerebral infarction; cerebral ischemia; heme oxygenase-1; oxidative stress..

Fig. (1)

The protective role of the Nrf2-HO-1 pathway in ischemic stroke. The redox imbalance in ischemic and reperfusion injury results in brain damage but also in an increase of HO-1. The increase in HO-1 together with ferritin, CO, biliverdin and bilirubin exert antioxidant, antiapoptitic, antiinflamatory and vasorelaxant effects, resulting in a protective effect against brain damage in ischemic stroke.

Fig. (2)

The relationship between cardiovascular risk factors and HO-1 expression. HO-1 expression is higher in patients with shorter (GT)n repeats, and higher levels of HO-1 are found in the presence of some stroke risk factors like hypertension, cigarette smoking, obesity and atherosclerosis. Higher HO-1 expression on the other hand decreases the risk of diabetes, decreases blood pressure, and protects against the progression of atherosclerosis.