Pioglitazone improves aortic wall elasticity in a rat model of elastocalcinotic arteriosclerosis

Specific treatment of age-related aortic wall arteriosclerosis and stiffening is lacking. Because ligands for peroxisome proliferator - activated receptor gamma 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 center dot 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 alpha and interleukin 1 beta. Pio increased nuclear peroxisome proliferator - activated receptor gamma immunostaining in the aortic wall, decreased tumor necrosis factor alpha ( P < 0.05 versus VDN Pio(-)), tended to decrease interleukin 1 beta mRNA expression ( P = 0.08 versus VDN Pio(-)), blunted aortic wall calcification (271 +/- 69, P < 0.05 versus VDN Pio(-) 562 +/- 87 mu mol center dot g(-1) dry weight) and prevented fragmentation of elastic fibers ( segments per 10 000 mu m(2): 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 center dot 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.