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(Hypertension. 2005;46:372.)
© 2005 American Heart Association, Inc.

Original Articles

Pioglitazone Improves Aortic Wall Elasticity in a Rat Model of Elastocalcinotic Arteriosclerosis

Virginie Gaillard; Daniel Casellas; Carole Seguin-Devaux; Hervé Schohn; Michel Dauça; Jeffrey Atkinson; Isabelle Lartaud

From the Unité Mixte UHP-INSERM U684, Pharmacology Laboratory Faculté de Pharmacie (V.G., J.A., I.L.), and Faculté de Médecine (C.S.-D.), Université Henri Poincaré Nancy-1, Nancy; Groupe Rein et Hypertension (EA3127) (D.C.), Institut Universitaire de Recherche Clinique, Montpellier; Peroxisome Proliferators (EA 3446) (H.S., M.D.), Faculté des Sciences et Techniques, Université Henri Poincaré Nancy-1, Nancy, France.

Correspondence to Jeffrey Atkinson, Pharmacology Laboratory, UHP-INSERM U684, Faculté de Pharmacie de l’Université Henri Poincaré, Nancy I, 5 rue Albert Lebrun, 54 000 Nancy, France. E-mail Jeffrey.Atkinson{at}pharma.uhp-nancy.fr

Specific treatment of age-related aortic wall arteriosclerosis and stiffening is lacking. Because ligands for peroxisome proliferator-activated receptor 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 and interleukin 1ß. Pio increased nuclear peroxisome proliferator-activated receptor immunostaining in the aortic wall, decreased tumor necrosis factor (P <0.05 versus VDN Pio^–), tended to decrease interleukin 1ß mRNA expression (P =0.08 versus VDN Pio^–), blunted aortic wall calcification (271±69, P <0.05 versus VDN Pio^– 562±87 µmol · g^–1 dry weight) and prevented fragmentation of elastic fibers (segments per 10 000 µm²: 8.4±0.3; P <0.05 versus VDN Pio^– 10.5±0.6). Pio reduced aortic wall stiffness (elastic modulus/wall stress: 4.8±0.6; P <0.05 versus VDN Pio^– 10.0±1.6), aortic pulse pressure (30±2 mm Hg; P <0.05 versus VDN Pio^– 39±4) and left ventricular hypertrophy (1.58±0.05 g · kg^–1; P <0.05 versus VDN Pio^– 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.

Key Words: extracellular matrix • peroxisome proliferator-activated receptor • arteriosclerosis • calcium • pulse pressure

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