Pioglitazone Improves Aortic Wall Elasticity in a Rat Model of Elastocalcinotic Arteriosclerosis
Autor: | Daniel Casellas, Hervé Schohn, Isabelle Lartaud, Virginie Gaillard, Jeffrey Atkinson, Michel Dauça, Carole Seguin-Devaux |
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Rok vydání: | 2005 |
Předmět: |
Male
medicine.medical_specialty Arteriosclerosis Aortic Diseases Aorta Thoracic Blood Pressure Left ventricular hypertrophy Monocytes Muscle hypertrophy Internal medicine medicine.artery Internal Medicine medicine Animals Rats Wistar Aortic Pulse Pressure Aorta Pioglitazone business.industry Macrophages Myocardium Calcinosis Organ Size Elastic Tissue medicine.disease Elasticity Rats Pulse pressure Hypervitaminosis D PPAR gamma Endocrinology Cytokines Hypertrophy Left Ventricular Thiazolidinediones business medicine.drug |
Zdroj: | Hypertension. 46:372-379 |
ISSN: | 1524-4563 0194-911X |
DOI: | 10.1161/01.hyp.0000171472.24422.33 |
Popis: | Specific treatment of age-related aortic wall arteriosclerosis and stiffening is lacking. Because ligands for peroxisome proliferator-activated receptor γ have beneficial effects on the arterial wall in atherosclerosis, via an antiinflammatory mechanism, we investigated whether long-term pioglitazone (Pio) treatment protects against another form of vascular wall disease, arteriosclerosis. We evaluated, in a rat model of elastocalcinotic arteriosclerosis (hypervitaminosis D and nicotine [VDN]), whether Pio (3 mg · kg −1 per day for 1.5 month PO) attenuated arteriosclerosis and its consequences: aortic wall rigidity, increased aortic pulse pressure, and left ventricular hypertrophy. In VDN rats, medial calcification was associated with monocyte/macrophage infiltration and induction of tumor necrosis factor α and interleukin 1β. Pio increased nuclear peroxisome proliferator-activated receptor γ immunostaining in the aortic wall, decreased tumor necrosis factor α ( P − ), tended to decrease interleukin 1β mRNA expression ( P =0.08 versus VDN Pio − ), blunted aortic wall calcification (271±69, P − 562±87 μmol · g −1 dry weight) and prevented fragmentation of elastic fibers (segments per 10 000 μm 2 : 8.4±0.3; P − 10.5±0.6). Pio reduced aortic wall stiffness (elastic modulus/wall stress: 4.8±0.6; P − 10.0±1.6), aortic pulse pressure (30±2 mm Hg; P − 39±4) and left ventricular hypertrophy (1.58±0.05 g · kg −1 ; P − 1.76±0.06). In conclusion, long-term Pio treatment attenuates aortic wall elastocalcinosis and, thus, lowers aortic wall stiffness, aortic pulse pressure, and left ventricular hypertrophy. |
Databáze: | OpenAIRE |
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