Dissociation between urate and blood pressure in mice and in people with early Parkinson's disease.

Autor:	Chen X; Department of Neurology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA. Electronic address: xchen17@mgh.harvard.edu., Umeh CC; Department of Neurology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA., Tainsh RE; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Gray-Bigelow 444, 55 Fruit Street, Boston, MA 02114, USA., Feng DD; Department of Neurology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA., Maguire M; Department of Neurology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA., Zuo F; Department of Neurology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA., Rahimian M; Department of Neurology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA., Logan R; Department of Neurology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA., Wang X; Department of Neurology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA., Ascherio A; Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA., Macklin EA; Statistics Center, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA., Buys ES; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Gray-Bigelow 444, 55 Fruit Street, Boston, MA 02114, USA., Schwarzschild MA; Department of Neurology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.
Jazyk:	angličtina
Zdroj:	EBioMedicine [EBioMedicine] 2018 Nov; Vol. 37, pp. 259-268. Date of Electronic Publication: 2018 Nov 08.
DOI:	10.1016/j.ebiom.2018.10.039
Abstrakt:	Background: Epidemiological, laboratory and clinical studies have established an association between elevated urate and high blood pressure (BP). However, the inference of causality remains controversial. A naturally occurring antioxidant, urate may also be neuroprotective, and urate-elevating treatment with its precursor inosine is currently under clinical development as a potential disease-modifying strategy for Parkinson's disease (PD). Methods: Our study takes advantage of a recently completed phase II trial evaluating oral inosine in de novo non-disabling early PD with no major cardiovascular and nephrological conditions, and of three lines of genetically engineered mice: urate oxidase (UOx) global knockout (gKO), conditional KO (cKO), and transgenic (Tg) mice with markedly elevated, mildly elevated, and substantially reduced serum urate, respectively, to systematically investigate effects of urate-modifying manipulation on BP. Findings: Among clinical trial participants, change in serum urate but not changes in systolic, diastolic and orthostatic BP differed by treatment group. There was no positive correlation between urate elevations and changes in systolic, diastolic and orthostatic BP ((p = .05 (in inverse direction), 0.30 and 0.63, respectively)). Between UOx gKO, cKO, or Tg mice and their respective wildtype littermates there were no significant differences in systolic or diastolic BP or in their responses to BP-regulating interventions. Interpretation: Our complementary preclinical and human studies of urate modulation in animal models and in generally healthy early PD do not support a hypertensive effect of urate elevation or an association between urate and BP. FUND: U.S. Department of Defense, RJG Foundation, Michael J. Fox Foundation LEAPS program, National Institutes of Health, American Federation for Aging Research, Parkinson's Disease Foundation Advancing Parkinson's Therapies initiative. (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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