Abstract-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-␤1, -␤2, and -␤3 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-␤ in the development and composition of advanced atherosclerotic lesions. In the present study, we show that inhibition of TGF-␤ signaling using a neutralizing anti-TGF-␤1, -␤2, and -␤3 antibody accelerates the development of atherosclerotic lesions in apoE-deficient mice. Moreover, inhibition of TGF-␤ signaling favors the development of lesions with increased inflammatory component and decreased collagen content. These results identify a major protective role for TGF-␤ in atherosclerosis.

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