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 . 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 1beta. 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 1beta mRNA expression (P =0.08 versus VDN Pio-), blunted aortic wall calcification (271+/-69, P <0.05 versus VDN Pio- 562+/-87 micromol . g(-1) dry weight) and prevented fragmentation of elastic fibers (segments per 10,000 microm2: 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.
Gaillard
Virginie
V
Pharmacology Laboratory, UHP-INSERM U684, Faculté de Pharmacie, l'Université Henri Poincaré, Nancy-1, 5 rue Albert Lebrun, 54000 Nancy, France.
Casellas
Daniel
D
Seguin-Devaux
Carole
C
Schohn
Hervé
H
Dauça
Michel
M
Atkinson
Jeffrey
J
Lartaud
Isabelle
I
D000818:Animals; D001011:Aorta / Q000473:pathology / Q000503:physiopathology*; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology; D001018:Aortic Diseases / Q000473:pathology / Q000503:physiopathology*; D001161:Arteriosclerosis / Q000473:pathology / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D002114:Calcinosis / Q000473:pathology / Q000503:physiopathology*; D016207:Cytokines / Q000378:metabolism; D004547:Elastic Tissue / Q000473:pathology / Q000503:physiopathology*; D004548:Elasticity; D017379:Hypertrophy, Left Ventricular / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D009000:Monocytes / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D047495:PPAR gamma / Q000378:metabolism; D000077205:Pioglitazone; D051381:Rats; D017208:Rats, Wistar; D045162:Thiazolidinediones / Q000494:pharmacology*
D016207:Cytokines; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077205:Pioglitazone