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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1864.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Parthenolide Modulates the NF-B–Mediated Inflammatory Responses in Experimental Atherosclerosis

Oscar López-Franco; Purificación Hernández-Vargas; Guadalupe Ortiz-Muñoz; Guillermo Sanjuán; Yusuke Suzuki; Luis Ortega; Julia Blanco; Jesús Egido; Carmen Gómez-Guerrero

From the Renal and Vascular Research Laboratory (O.L.-F., P.H.-V., G.O.-M., G.S., J.E., C.G.-G.), Fundación Jiménez Díaz, Autónoma University, Madrid, Spain; the Division of Nephrology, Department of Internal Medicine (Y.S.), Juntendo University School of Medicine, Tokyo, Japan; and the Hospital Clínico San Carlos (L.O., J.B.), Complutense University, Madrid, Spain.

Correspondence to Carmen Gómez-Guerrero, PhD, Renal and Vascular Research Lab, Fundación Jiménez Díaz (Autónoma University), Avda. Reyes Católicos, 2 28040 Madrid, Spain. E-mail cgomez{at}fjd.es

Objective— Activation of transcription factor NF-B 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-B inhibitor.

Methods and Results— In vascular smooth muscle cells (VSMCs) and monocytes stimulated with lipopolysaccharide (LPS), nontoxic doses of PTN reduced IB degradation, NF-B 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-B activity, but not AP-1, in the lesions. Moreover, PTN affects neither apoptotic cell death nor oxidative stress in cultured cells and mice.

Conclusion— NF-B 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.

PTN inhibits the NF-B activation and expression of regulated genes in cultured VSMCs and monocytes. PTN protects against the development of atherosclerosis in apoE mice by inhibition of NF-B and reduction of inflammatory cell infiltration. PTN treatment may represent a novel therapeutic approach to atherosclerosis.

Key Words: NF-B • atherosclerosis • parthenolide • apoE • inflammation

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