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

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

49 Citations (Scopus)

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<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 -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.

Original languageEnglish
Pages (from-to)372-379
Number of pages8
JournalHypertension
Volume46
Issue number2
DOIs
Publication statusPublished - Aug 2005
Externally publishedYes

Keywords

  • Arteriosclerosis
  • Calcium
  • Extracellular matrix
  • Peroxisome proliferator-activated receptor
  • Pulse pressure

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