Circulation Research. 2001
Published online before print September 27, 2001, doi: 10.1161/hh2201.099415
Published online before print September 27, 2001, doi: 10.1161/hh2201.099415
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Submitted on May 29, 2001
Revised on September 12, 2001
Accepted on September 19, 2001
Inhibition of Transforming Growth Factor-ß Signaling Accelerates Atherosclerosis and Induces an Unstable Plaque Phenotype in Mice
From the Institut National de la Santé et de la Recherche Médicale (Z.M., A.G., B.E., R.M., A.T.), INSERM U541, Institut Fédératif de Recherche "Circulation Paris 7," Hôpital Lariboisière; and ICGM-INSERM U477, Hôpital Cochin (C. M.-F., C.K., D.F.), Paris, France.
* To whom correspondence should be addressed. E-mail: ziad.mallat{at}inserm.lrb.ap-hop-paris.fr.
Atherosclerosis is a disease of the arterial wall that seems to be tightly modulated by the local inflammatory balance. Whereas a large body of evidence supports a role for proinflammatory mediators in disease progression, the understanding of the role of the antiinflammatory component in the modulation of plaque progression is only at its beginning. TGF-ß1, -ß2, and -ß3 are cytokines/growth factors with broad activities on cells and tissues in the cardiovascular system and have been proposed to play a role in the pathogenesis of atherosclerosis. However, no study has examined the direct role of TGF-ß in the development and composition of advanced atherosclerotic lesions. In the present study, we show that inhibition of TGF-ß signaling using a neutralizing anti--TGF-ß1, -ß2, and -ß3 antibody accelerates the development of atherosclerotic lesions in apoE-deficient mice. Moreover, inhibition of TGF-ß signaling favors the development of lesions with increased inflammatory component and decreased collagen content. These results identify a major protective role for TGF-ß in atherosclerosis.
Key words: atherosclerosis • cytokines • inflammation • macrophages • lymphocytes
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H. Williams, J. L. Johnson, K. G. S. Carson, and C. L. Jackson Characteristics of Intact and Ruptured Atherosclerotic Plaques in Brachiocephalic Arteries of Apolipoprotein E Knockout Mice Arterioscler Thromb Vasc Biol, May 1, 2002; 22(5): 788 - 792. [Abstract] [Full Text] [PDF]
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E. Lutgens and M. J.A.P. Daemen Transforming Growth Factor-{beta}: A Local or Systemic Mediator of Plaque Stability? Circ. Res., November 9, 2001; 89(10): 853 - 855. [Full Text] [PDF]
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