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

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 46; no. 2; pp. 372 - 379
• Main Authors: Gaillard, Virginie, Casellas, Daniel, Seguin-Devaux, Carole, Schohn, Hervé, Dauça, Michel, Atkinson, Jeffrey, Lartaud, Isabelle
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01-08-2005; Hagerstown, MD Lippincott
• Subjects: Animals; Aorta - pathology; Aorta - physiopathology; Aorta, Thoracic - metabolism; Aorta, Thoracic - pathology; Aortic Diseases - pathology; Aortic Diseases - physiopathology; Arterial hypertension. Arterial hypotension; Arteriosclerosis - pathology; Arteriosclerosis - physiopathology; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure - drug effects; Calcinosis - pathology; Calcinosis - physiopathology; Cardiology. Vascular system; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Cytokines - metabolism; Elastic Tissue - pathology; Elastic Tissue - physiopathology; Elasticity; Experimental diseases; Hypertrophy, Left Ventricular - pathology; Macrophages - pathology; Male; Medical sciences; Monocytes - pathology; Myocardium - pathology; Organ Size - drug effects; PPAR gamma - metabolism; Rats; Rats, Wistar; Thiazolidinediones - pharmacology; Immunohistochemistry; Nuclear receptor; Calcium; Rat; Elasticity; Cardiovascular disease; Inorganic element; Vascular disease; Alkaloid; Hypoglycemic agent; arteriosclerosis; Atherosclerosis; Aorta; Extracellular matrix; Stiffness; peroxisome proliferator-activated receptor; Vascular wall; Elastic modulus; pulse pressure; Monocyte; Pioglitazone; Rodentia; Antiinflammatory agent; Interleukin 1β; Thiazolidinedione derivatives; Stress; Left ventricle; Vertebrata; Mammalia; Treatment; Tumor necrosis factor; Animal; Calcification; Elastic fiber; Infiltration; Comparative study; Macrophage; Nicotine
• DOI: 10.1161/01.HYP.0000171472.24422.33
• EISSN: 1524-4563
• ISSN: 0194-911X

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 per day for 1.5 month PO) attenuated arteriosclerosis and its consequencesaortic 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<0.05 versus VDN Pio), tended to decrease interleukin 1β mRNA expression (P=0.08 versus VDN Pio), blunted aortic wall calcification (271±69, P<0.05 versus VDN Pio 562±87 μmol · g dry weight) and prevented fragmentation of elastic fibers (segments per 10 000 μm8.4±0.3; P<0.05 versus VDN Pio 10.5±0.6). Pio reduced aortic wall stiffness (elastic modulus/wall stress4.8±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; 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.