Lack of glutathione peroxidase 1 accelerates cardiac-specific hypertrophy and dysfunction in angiotensin II hypertension.
Glutathione peroxidase 1 (Gpx1) plays an important role in cellular defense by converting hydrogen peroxide and organic hydroperoxides to nonreactive products, and Gpx1(-/-) mice, which are characterized by reduced tissue glutathione peroxidase activity, are known to exhibit enhanced oxidative stress. Peroxides participate in tissue injury, as well as the hypertrophy of cultured cells, yet the role of Gpx1 to prevent end organ damage in cardiovascular tissue is not clear. We postulated that Gpx1 deletion would potentiate both aortic and cardiac hypertrophy, as well as mean arterial blood pressure, in response to angiotensin II (AngII). Our results show that short-term AngII markedly increased left ventricular mass, myocyte cross-sectional area, and interventricular septum thickness and decreased shortening fraction in Gpx1(-/-) mice as compared with wild-type animals. On the other hand, AngII resulted in a similar increase in mean arterial blood pressure in wild-type and Gpx1(-/-) mice. Collagen deposition increased in response to AngII, but no differences were found between strains. Vascular hypertrophy increased to the same extent in Gpx1(-/-) and wild-type mice. Collectively, our results indicate that Gpx1 deficiency accelerates cardiac hypertrophy and dysfunction but has no effect on vascular hypertrophy and mean arterial blood pressure and suggest a major role for Gpx1 in cardiac dysfunction in AngII-dependent hypertension.
Ardanaz
Noelia
N
Department of Pharmacology and Chemical Biology and Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Yang
Xiao-Ping
XP
Cifuentes
M Eugenia
ME
Haurani
Mounir J
MJ
Jackson
Kyle W
KW
Liao
Tang-Dong
TD
Carretero
Oscar A
OA
Pagano
Patrick J
PJ
D000804:Angiotensin II; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001794:Blood Pressure; D015153:Blotting, Western; D001835:Body Weight; D006332:Cardiomegaly / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D004452:Echocardiography; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism*; D006321:Heart / Q000503:physiopathology; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018487:Ventricular Dysfunction, Left / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D000094765:Glutathione Peroxidase GPX1
D000804:Angiotensin II; D005979:Glutathione Peroxidase; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse