20-Hydroxyeicosatetraenoic Acid Inhibition Attenuates Balloon Injury-Induced Neointima Formation and Vascular Remodeling in Rat Carotid Arteries

Autor: Richard J. Roman, Rodney C. Baker, Huiling Liu, Ludwig D. Orozco, Eddie Perkins, Betty Chen, Fan Fan, Daryl A. Johnson
Rok vydání: 2013
Předmět:
Male
Neointima
medicine.medical_specialty
Vascular smooth muscle
Intimal hyperplasia
Carotid Artery
Common
Amidines
Muscle
Smooth
Vascular
Rats
Sprague-Dawley
Drug Discovery and Translational Medicine
chemistry.chemical_compound
Cytochrome P-450 Enzyme System
Cell Movement
medicine.artery
Internal medicine
Hydroxyeicosatetraenoic Acids
Animals
Cytochrome P-450 Enzyme Inhibitors
Medicine
Carotid Stenosis
Cytochrome P450 Family 4
Common carotid artery
Angioplasty
Balloon
Coronary
Enzyme Inhibitors
Cell Proliferation
Pharmacology
Hyperplasia
business.industry
Hydroxyeicosatetraenoic acid
Anatomy
Triazoles
medicine.disease
20-Hydroxyeicosatetraenoic acid
Tunica intima
Rats
Disease Models
Animal
Endocrinology
medicine.anatomical_structure
chemistry
cardiovascular system
Molecular Medicine
Cytochrome P-450 CYP4A
Carotid Artery Injuries
Tunica Intima
business
Zdroj: Journal of Pharmacology and Experimental Therapeutics. 346:67-74
ISSN: 1521-0103
0022-3565
DOI: 10.1124/jpet.113.203844
Popis: 20-Hydroxyeicosatetraenoic acid (20-HETE) contributes to the migration and proliferation of vascular smooth muscle cells (VSMC) in vitro, but there are few studies that address its effects on vascular remodeling in vivo. The present study determined whether inhibition of 20-HETE production attenuates intimal hyperplasia (IH) and vascular remodeling after balloon injury (BI). Sprague Dawley rats underwent BI of the common carotid artery and were treated with vehicle, 1-aminobenzotriazole (ABT, 50 mg/kg i.p. once daily), or HET0016 (N-hydroxy-N′-(4-butyl-2-methylphenyl)-formamidine) (2 mg/kg s.c. twice daily) for 14 days. Fourteen days after BI and treatment, the animals underwent carotid angiography, and the arteries were harvested for morphometric, enzymatic and immunohistochemical analysis. There was a 96% reduction of angiographic stenosis in the rats treated with 1-ABT. There was a 61 and 66% reduction of the intima/media area ratios in the 1-ABT and HET0016 treated rats compared with the vehicle-treated group. 20-HETE levels were elevated in BI carotid arteries, and the levels were markedly suppressed in the groups treated with 1-ABT and HET0016 (P < 0.001). Immunostaining revealed that the expression of CYP4A enzyme was markedly increased in the neointima of BI arteries, and it colocalized with the expression of smooth muscle-specific actin, indicating increased proliferation of VSMC. An increase in the expression of CYP4A and the production of 20-HETE contributes to neointimal growth in BI rat carotid arteries. Systemic administration 1-ABT or HET0016 prevents the increase in 20-HETE levels and attenuates VSMC migration and proliferation, resulting in a marked reduction in IH and vascular remodeling after endothelial injury.
Databáze: OpenAIRE
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