title: Genetic variant-associated endothelial dysfunction behind small-vessel cerebral circulatory disorders: a new pathomechanism behind common cerebral phenotypes.
abstract: An increasing body of evidence suggests that different genetic factors, such as angiotensin-converting enzyme (ACE) I/D, angiotensin II type-1 receptor (AT1R) A1166C, methylenetetrahydrofolate reductase (MTHFR) C677T and ENOS G894T variants are associated with an endothelial dysfunction (ED). EDs are relatively new phenomena that are presumed to contribute to vasoregulatory malfunctions at the small-vessel level. Ever more clinical observations indicate that the above genetic variants are also associated with cerebral small-vessel disorders. This article reviews the knowledge available on the roles of ED- associated genetic variants in cerebral circulatory disorders, and suggests that EDs can be causative factors for different common cerebral pathologies such as leukoaraiosis or/and small-vessel infarcts. Newly-developed drugs involving phosphodiesterase type-5 inhibitors, which improve the endothelial functions, may comprise a new approach to the treatment and prevention of small-vessel cerebral circulatory disorders.
authors.affiliation: Department of Neurology and Neurophysiology, Pandy Kalman County Hospital, Gyula, H-5600 Békéscsaba, Pipacs köz 9, Hungary. szolnoki99@hotmail.com
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Szolnoki
mesh_terms: D002196:Capillaries / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000235:genetics; D002561:Cerebrovascular Disorders / Q000235:genetics*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D014644:Genetic Variation; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D012084:Renin-Angiotensin System / Q000235:genetics*
chemical_list: D052250:Nitric Oxide Synthase Type III; D042965:Methylenetetrahydrofolate Reductase (NADPH2)