HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Pactimibe stabilizes atherosclerotic plaque through macrophage acyl-CoA:cholesterol acyltransferase inhibition in WHHL rabbits.

Abstract
Novel acyl coenzyme A:cholesterol acyltransferase (ACAT) inhibitor pactimibe was administered as the sulfate salt form to 3-month-old homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits at doses of 0, 10, or 30 mg/kg for 32 weeks. Pactimibe (10 and 30 mg/kg) tended to reduce intimal thickening in thoracic aortic lesions (294+/-39 and 276+/-32 microm, respectively, versus 313+/-37 microm control), histopathological examination revealing significantly increased smooth muscle cell area (12.0+/-0.9% and 12.3+/-0.5%, P<0.05, respectively, versus 9.7+/-0.8% control), significantly increased collagen fiber area (20.5+/-1.2% and 31.0+/-1.3%, P<0.05, respectively, versus 16.2+/-1.0% control), and tended to reduce macrophage infiltration (6.0+/-1.1% and 4.6+/-1.0%, respectively, versus 7.0+/-1.3% control). Pactimibe dose-dependently reduced cholesteryl ester content in thoracic and abdominal aortic lesions, and reduced free cholesterol content in the aorta versus control. Although pactimibe did not alter serum cholesterol levels in WHHL rabbits, it stabilized vulnerable plaque characterized with reduced cholesteryl ester content, enriched collagen fibers and increased smooth muscle cells, indicating potential as a treatment strategy for coronary heart disease.
AuthorsKen Kitayama, Teiichiro Koga, Naoyuki Maeda, Toshimori Inaba, Tomoyuki Fujioka
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 539 Issue 1-2 Pg. 81-8 (Jun 06 2006) ISSN: 0014-2999 [Print] Netherlands
PMID16690054 (Publication Type: Journal Article)
Chemical References
  • Cholesterol Esters
  • Indoleacetic Acids
  • Collagen
  • pactimibe
  • Sterol O-Acyltransferase
Topics
  • Animals
  • Aorta (metabolism, pathology)
  • Atherosclerosis (drug therapy, etiology, pathology)
  • Cholesterol Esters (biosynthesis)
  • Collagen (metabolism)
  • Extracellular Matrix (metabolism)
  • Hyperlipidemias (complications, genetics)
  • Indoleacetic Acids (pharmacology, therapeutic use)
  • Macrophages (enzymology, pathology)
  • Muscle, Smooth, Vascular (metabolism, pathology)
  • Rabbits
  • Sterol O-Acyltransferase (antagonists & inhibitors)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: