Heme Oxygenase-1, Cardiac Senescence, and Myocardial Infarction: A Critical Review of the Triptych

Purpose: Heme oxygenase-1 (HO-1) is a crucial enzyme in heme metabolism, facilitating the breakdown of heme into biliverdin, carbon monoxide, and free iron. Renowned for its potent cytoprotective properties, HO-1 showcases notable antioxidant, anti-inflammatory, and anti-apoptotic effects. In this review, the authors aim to explore the profound impact of HO-1 on cardiac senescence and its potential implications in myocardial infarction (MI). Results: Recent research has unveiled the intricate role of HO-1 in cellular senescence, characterized by irreversible growth arrest and functional decline. Notably, cardiac senescence has emerged as a pivotal factor in the development of various cardiovascular conditions, including MI. Notably, cardiac senescence has emerged as an important factor in the development of various cardiovascular conditions, including myocardial infarction (MI). The accumulation of senescent cells, spanning vascular endothelial cells, vascular smooth muscle cells, cardiomyocytes, and progenitor cells, poses a significant risk for cardiovascular diseases such as vascular aging, atherosclerosis, myocardial infarction, and ventricular remodeling. Inhibition of cardiomyocyte senescence not only reduces senescence-associated inflammation but also impacts other myocardial lineages, hinting at a broader mechanism of propagation in pathological remodeling. HO-1 has been shown to improve heart function and mitigate cardiomyocyte senescence induced by ischemic injury and aging. Furthermore, HO-1 induction has been found to alleviate H₂O₂-induced cardiomyocyte senescence. As we grow in our understanding of antiproliferative, antiangiogenic, anti-aging, and vascular effects of HO-1, we see the potential to exploit potential links between individual susceptibility to cardiac senescence and myocardial infarction. Conclusions: This review investigates strategies for upregulating HO-1, including gene targeting and pharmacological agents, as potential therapeutic approaches. By synthesizing compelling evidence from diverse experimental models and clinical investigations, this study elucidates the therapeutic potential of targeting HO-1 as an innovative strategy to mitigate cardiac senescence and improve outcomes in myocardial infarction, emphasizing the need for further research in this field. Graphical Abstract: This graphical abstract depicts the complex interplay between heme oxygenase-1 and cardiac senescence and the potential application of HO-1 in myocardial infarction. The figure depicts the intricate relationship between heme oxygenase-1 (HO-1) and cardiac senescence, highlighting their interplay in the context of myocardial infarction (MI) and the potential therapeutic application of HO-1. Senescent cardiomyocytes actively participate in pathological myocardial remodeling, influencing outcomes in MI. Importantly, inhibition of cardiomyocyte senescence leads to a reduction in senescence-associated inflammation and markers within other myocardial lineages, supporting the hypothesis that senescent (Figure presented.)