Abstract
Heme oxygenase-1 (HO-1) catalyzes the degradation of heme into carbon monoxide (CO), iron, and biliverdin, which is rapidly metabolized to bilirubin. The activation of vascular smooth muscle cells (SMCs) plays a critical role in mediating the aberrant arterial response to injury and a number of vascular diseases. Pharmacological induction or gene transfer of HO-1 improves arterial remodeling in animal models of post-angioplasty restenosis, vascular access failure, atherosclerosis, transplant arteriosclerosis, vein grafting, and pulmonary arterial hypertension, whereas genetic loss of HO-1 exacerbates the remodeling response. The vasoprotection evoked by HO-1 is largely ascribed to the generation of CO and/or the bile pigments, biliverdin and bilirubin, which exert potent antioxidant and anti-inflammatory effects. In addition, these molecules inhibit vascular SMC proliferation, migration, apoptosis, and phenotypic switching. Several therapeutic strategies are currently being pursued that may allow for the targeting of HO-1 in arterial remodeling in various pathologies, including the use of gene delivery approaches, the development of novel inducers of the enzyme, and the administration of unique formulations of CO and bilirubin.
Highlights
Arteries transport blood from the heart to all other tissues and organs
The tunica intima forms the innermost layer of the vessel, and it consists of a single layer of endothelial cells that serves as a barrier between the blood-carrying lumen and vessel wall
We showed that the carbon monoxide (CO)-scavenger, hemoglobin, augments mitogenesis in vascular smooth muscle cells (SMCs) following the induction of Heme oxygenase-1 (HO-1) [37]
Summary
Arteries transport blood from the heart to all other tissues and organs They consist of multiple cell types and structural proteins arranged in three concentric layers: the tunica intima, the tunica media, and the tunica adventitia [1]. Antioxidants 2020, 9, 829 switching where they lose their contractility markers and differentiate to a synthetic phenotype [3] These synthetic cells display high rates of proliferation and synthesize matrix metalloproteinases that promotes SMC migration from the media to the intima by separating these cells from the basement membrane and extracellular matrix. This leads to the formation of a neointima that impairs blood flow. It will highlight potential therapeutic modalities in targeting HO-1 and its products in the treatment of occlusive vascular disease
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