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(Hypertension. 2005;46:1180.)
© 2005 American Heart Association, Inc.

Original Articles

Lipid Accumulation and Transforming Growth Factor-ß Upregulation in the Kidneys of Rats Administered Angiotensin II

Kan Saito; Nobukazu Ishizaka; Masumi Hara; Gen Matsuzaki; Masataka Sata; Ichiro Mori; Minoru Ohno; Ryozo Nagai

From the Departments of Cardiovascular Medicine (N.I., K.S., G.M., M.S., M.O., N.R.), and Diabetes and Metabolic Disease (M.H.), University of Tokyo Graduate School of Medicine, Japan; and Department of Pathology (I.M.), Wakayama Medical College, Japan.

Reprint requests to Nobukazu Ishizaka, MD, PhD, Department of Cardiovascular Medicine, University of Tokyo, Graduate School of Medicine, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan. E-mail nobuishizka-tky{at}umin.ac.jp

Abnormal lipid metabolism may play a role in progressive renal failure. We studied whether lipid accumulation occurs and whether lipid deposits are colocalized with transforming growth factor-ß1 (TGF-ß1) in the kidney of angiotensin II–infused animals. Oil red O staining showed marked lipid deposition in the tubular epithelial and vascular wall cells of angiotensin II–treated but not in norepinephrine-treated rats. Histological analyses showed that increased amounts of superoxide and intense TGF-ß1 mRNA expression were present in lipid-positive tubular epithelial cells in angiotensin II–infused animals. Protein expression of sterol regulatory element-binding protein 1 (SREBP-1) and mRNA expression of fatty acid synthase in the kidney were &3 times and 1.5 times, respectively, higher in angiotensin II–treated rats than in controls. Treatment of angiotensin II–infused animals with an iron chelator, deferoxamine, attenuated the angiotensin II–induced increases in renal expression of SREBP-1 and fatty acid synthase and normalized the lipid content in the renal cortical tissues. Abnormal lipid metabolism may be associated with upregulation of TGF-ß1 expression and aberrant iron homeostasis in the kidneys of angiotensin II–infused animals.

Key Words: angiotensin II • transforming growth factors • lipids

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