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

Abstract

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.