Beneficial and Detrimental Roles of Heme Oxygenase-1 in the Neurovascular System
Yoon Kyung Choi, Young‐Myeong Kim
Abstract
Heme oxygenase (HO) has both beneficial and detrimental effects via its metabolites, including carbon monoxide (CO), biliverdin or bilirubin, and ferrous iron. HO-1 is an inducible form of HO that is upregulated by oxidative stress, nitric oxide, CO, and hypoxia, whereas HO-2 is a constitutive form that regulates vascular tone and homeostasis. In brains injured by trauma, ischemia-reperfusion, or Alzheimer's disease (AD), the long-term expression of HO-1 can be detected, which can lead to cytotoxic ferroptosis via iron accumulation. In contrast, the transient induction of HO-1 in the peri-injured region may have regenerative potential (e.g., angiogenesis, neurogenesis, and mitochondrial biogenesis) and neurovascular protective effects through the CO-mediated signaling pathway, the antioxidant properties of bilirubin, and the iron-mediated ferritin synthesis. In this review, we discuss the dual roles of HO-1 and its metabolites in various neurovascular diseases, including age-related macular degeneration, ischemia-reperfusion injury, traumatic brain injury, Gilbert's syndrome, and AD.