Figure 5.

Targeting heme oxygenase-1 (HO-1) and its products in arterial remodeling. Arterial injury or disease triggers the proliferation, migration, death, and dedifferentiation of vascular smooth muscle cells (SMCs), leading to the formation of a neointima. Several strategies may be used to harness the therapeutic potential of HO-1 to block SMC activation and neointima formation in various pathologies. Pharmacological inducers, including nutraceuticals (NC), bardoxolone methyl (BM), dimethylfumurate (DMF), and canagliflozin (CANA), provide a promising approach in stimulating HO-1 expression. Similarly, gene therapy using retroviruses (RV), adenoviruses (AV), adeno-associated viruses (AAV), herpes simplex virus (HSV), lentivirus (LV), or non-viral methods represents an attractive mode of delivering HO-1 to tissues. Alternatively, CO can be administered via gas inhalation or through the use of CO-releasing molecules (CORMs), prodrugs that generate CO, and aqueous solutions of CO. In addition, biliverdin or pegylated bilirubin (PEG-bilirubin) may be directly administered, or pharmacological inhibitors of uridine 5′-diphopho-glucuronlytransferase 1A1 (UGT1A1) alone, or in combination with HO-1 inducers, may be utilized to increase circulating levels of bilirubin.