Tetrahidrobiopterin ve Kardiyovasküler Hastalıklar
Synopsis
Tetrahydrobiopterin (BH4) is an endogenous cofactor involved in the enzymatic conversions of essential biomolecules, including nitric oxide (NO), tyrosine, serotonin, and phenylalanine. Synthesized from guanosine triphosphate (GTP), BH4 plays critical biological roles in nervous, immune, endocrine, and cardiovascular system functions. Under oxidative stress, the oxidation of BH4 to BH2 or a reduction in its synthesis leads to the functional uncoupling of nitric oxide synthase (NOS). Uncoupled NOS produces reactive oxygen species instead of nitric oxide, disrupting the nitro-redox balance and causing adverse cardiovascular outcomes. This biochemical impairment induces vascular dysfunctions such as pulmonary hypertension, hypertension, atherosclerosis, and ischemic heart disease. In pulmonary hypertension, BH4 deficiency causes selective pulmonary pathology, while BH4 administration stimulates vasodilation and prevents disease progression. In hypertension, BH4-NOS uncoupling impairs vascular relaxation, elevating peripheral resistance and blood pressure; BH4 supplementation lowers blood pressure and enhances the repair capacity of circulating endothelial progenitor cells. In atherosclerosis, reduced NO levels contribute to platelet adhesion and smooth muscle cell proliferation, whereas BH4 or sepiapterin treatment reverses endothelial dysfunction. In ischemia and reperfusion injury, decreased BH4 bioavailability leads to cardiac tissue loss and infarction, while BH4 replacement increases NO production and protects myocardial function. Consequently, BH4 holds significant therapeutic potential in the prevention and treatment of cardiovascular diseases.
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