title: Parthenolide modulates the NF-kappaB-mediated inflammatory responses in experimental atherosclerosis.
abstract: OBJECTIVE
  Activation of transcription factor NF-kappaB is an important step in the development of vascular damage, because it controls inducible genes, including many inflammatory mediators. The pharmacological modulation of this process is the main objective in the design of new therapies for atherosclerosis. In this work we analyzed the effects of the natural compound parthenolide (PTN), an NF-kappaB inhibitor.
  
  
  RESULTS
  In vascular smooth muscle cells (VSMCs) and monocytes stimulated with lipopolysaccharide (LPS), nontoxic doses of PTN reduced IkappaBalpha degradation, NF-kappaB activation, and MCP-1 expression, without inhibiting AP-1 and MAPK. In apoE mice, treatment with low (2 mg/kg, 20 weeks), medium (4 mg/kg, 10 weeks), and high (10 mg/kg, 10 weeks) dose of PTN reduced the size of aortic lesion, decreased macrophage, and increased VSMC content in the lesions. Treated mice showed reduced serum levels of MCP-1 and attenuated NF-kappaB activity, but not AP-1, in the lesions. Moreover, PTN affects neither apoptotic cell death nor oxidative stress in cultured cells and mice.
  
  
  CONCLUSIONS
  NF-kappaB inhibition by PTN retards atherosclerotic lesions in apoE mice, by reducing lesion size and changing plaque composition. This natural compound could represent a novel therapeutic approach to inflammation during vascular damage.
authors.affiliation: Renal and Vascular Research Laboratory, Fundación Jiménez Díaz, Autónoma University, Avda. Reyes Católicos, 2 28040 Madrid, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: López-Franco
authors.forename: Purificación
authors.initials: P
authors.lastname: Hernández-Vargas
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Ortiz-Muñoz
authors.forename: Guillermo
authors.initials: G
authors.lastname: Sanjuán
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Luis
authors.initials: L
authors.lastname: Ortega
authors.forename: Julia
authors.initials: J
authors.lastname: Blanco
authors.forename: Jesús
authors.initials: J
authors.lastname: Egido
authors.forename: Carmen
authors.initials: C
authors.lastname: Gómez-Guerrero
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004041:Dietary Fats / Q000008:administration & dosage; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000473:pathology*; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D012717:Sesquiterpenes / Q000494:pharmacology*
chemical_list: D004041:Dietary Fats; D016328:NF-kappa B; D012717:Sesquiterpenes; C002669:parthenolide