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Hyperhomocysteinemia impairs regional blood flow: involvements of endothelial and neuronal nitric oxide

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Abstract

Increasing evidence support the idea that hyperhomocysteinemia (HHcy) is responsible for pathogenesis underlying cerebral, coronary, renal, and other vascular circulatory disorders and for hypertension. Impaired synthesis of nitric oxide (NO) in the endothelium or increased production of asymmetric dimethylarginine and activated oxygen species are involved in the impairment of vasodilator effects of NO. Impaired circulation in the brain derived from reduced synthesis and actions of NO would be an important triggering factor to dementia and Alzheimer’s disease. Reduced actions of NO and brain hypoperfusion trigger increased production of amyloid-β that inhibits endothelial function, thus establishing a vicious cycle for impairing brain circulation. HHcy is involved in the genesis of anginal attack and coronary myocardial infarction. HHcy is also involved in renal circulatory diseases. The homocysteine (Hcy)-induced circulatory failure is promoted by methionine and is prevented by increased folic acid and vitamin B6/B12. Eliminating poor life styles, such as smoking and being sedentary; keeping favorable dietary habits; and early treatment maintaining constitutive NOS functions healthy, reducing oxidative stresses would be beneficial in protecting HHcy-induced circulatory failures.

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Abbreviations

ACh:

Acetylcholine

Aβ:

Amyloid-β

AD:

Alzheimer’s disease

ADMA:

Asymmetric dimethylarginine

AβPP:

Aβ-protein precursor (AβPP)

DDAH:

Dimethylaminohydrolase

EPC:

Endothelial progenitor cell

GABA:

γ-Amino butylic acid

Hcy:

Homocysteine

HHcy:

Hyperhomocysteinemia

NO:

Nitric oxide

PPARγ:

Peroxisome proliferator-activated receptor-γ

SOD:

Superoxide dismutase

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Toda, N., Okamura, T. Hyperhomocysteinemia impairs regional blood flow: involvements of endothelial and neuronal nitric oxide. Pflugers Arch - Eur J Physiol 468, 1517–1525 (2016). https://doi.org/10.1007/s00424-016-1849-y

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