Ursolic acid inhibits neointima formation in the rat carotid artery injury model.
Triterpenoids are natural compounds that are found in a large variety of plants and vegetarian foods, and are used for medicinal purposes in many Asian countries. Pentacyclic triterpenes, such as ursolic acid, have been reported to exhibit anticancer and anti-inflammatory properties. The present study was designed to assess the effects of ursolic acid in the migration and proliferation of vascular smooth muscle cells (VSMC), and in a vascular injury model. The exposure of VSMC to ursolic acid results in a chemotaxis inhibition, in a reduction of the expression of proliferating cell nuclear antigen (PCNA) and in a disorganization of beta-tubulin and vimentin cytoskeletal proteins. Administration of ursolic acid in the rat carotid balloon catheter injury model shows a significant inhibition of neointimal hyperplasia. Thus, we have demonstrated that daily doses of 6 mg/kg body weight for 10 days reduce both the ratio of intimal to medial areas and the degree of stenosis by 80%, and suppress the expression of PCNA in both neointima and media. These results suggest that pentacyclic triterpenes may be of potential therapeutic value in vascular injury, and a possible treatment strategy for the prevention of the progression of atherosclerosis and restenosis after angioplasty.
Pozo
Mayte
M
Vascular Pathology Laboratory, Fundación Jiménez Díaz, Universidad Autónoma, Avenida Reyes Católicos, 2, 28040 Madrid, Spain.
Castilla
Virginia
V
Gutierrez
Cristina
C
de Nicolás
Rosario
R
Egido
Jesús
J
González-Cabrero
Jesús
J
D000818:Animals; D020212:Carotid Artery Injuries / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D017536:Carotid Artery, Common; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005500:Follow-Up Studies; D006965:Hyperplasia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000517:prevention & control; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014315:Triterpenes / Q000627:therapeutic use*; D014404:Tubulin / Q000187:drug effects / Q000378:metabolism; D017539:Tunica Intima / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D014746:Vimentin / Q000187:drug effects / Q000378:metabolism; D000097245:Ursolic Acid
D016861:Cyclooxygenase Inhibitors; D018809:Proliferating Cell Nuclear Antigen; D014315:Triterpenes; D014404:Tubulin; D014746:Vimentin; D000097245:Ursolic Acid