Peroxisome proliferator ameliorates endothelial dysfunction in a murine model of hyperhomocysteinemia

• Published in: American journal of physiology. Lung cellular and molecular physiology 2003-02, Vol.284 (2), p.333-L341
• Main Authors: Sood, Harpreet S, Hunt, Matthew J, Tyagi, Suresh C
• Format: Article
• Language: English
• Subjects: Animals; Aorta - enzymology; Aorta - pathology; Aorta - physiopathology; Blood Pressure; Clofibric Acid - analogs & derivatives; Clofibric Acid - pharmacology; Cystathionine beta-Synthase - genetics; Endothelium, Vascular - physiopathology; Enzyme Activation; Fibric Acids; Genotype; Homocysteine - blood; Hyperhomocysteinemia - complications; Hyperhomocysteinemia - genetics; Hyperhomocysteinemia - pathology; Hyperhomocysteinemia - physiopathology; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases - metabolism; Mice; Mice, Inbred C57BL; Mice, Mutant Strains - genetics; Peroxisome Proliferators - metabolism; Phenotype; Proteinuria - etiology; Tyrosine - analogs & derivatives; Tyrosine - biosynthesis
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00183.2002

Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi 39216 To test the hypothesis that endothelial dysfunction in hyperhomocysteinemia was due to increased levels of nitrotyrosine and matrix metalloproteinase (MMP) activity in response to antagonism of peroxisome proliferator-activated receptor- (PPAR- ), cystathionine -synthase (CBS) /+ mice were bred, tail tissue was analyzed for genotype by PCR, and tail vein blood was analyzed for homocysteine (Hcy) by spectrofluorometry. To induce PPAR- , mice were administered 8 µg/ml of ciprofibrate (CF) and grouped: 1 ) wild type (WT), 2 ) WT + CF, 3 ) CBS, 4) CBS + CF ( n  = 6 in each group). In these four groups of mice, plasma Hcy was 3.0 ± 0.2, 2.5 ± 1.2, 15.2 ± 2.6   ( P