Role of transforming growth factor-beta1/Smads in regulating vascular inflammation and atherogenesis.
Accumulating evidence supports the role of inflammation in the development of a variety of chronic vascular diseases such as atherosclerosis, transplantation arteriosclerosis, and restenosis after vascular mechanical injury. Thus, identification of mechanisms to control inflammation may provide novel therapeutic targets to limit such disease states. Transforming growth factor-beta1 (TGF-beta1) is a pleiotropic growth factor with potent immunomodulating effects on cells important to atherosclerotic lesion formation including endothelial cells, vascular smooth muscle cells, macrophages, and T cells. The mechanisms responsible for the protective, anti-inflammatory effects of TGF-beta1 have recently become elucidated. This review focuses on the emerging role of the downstream TGF-beta1 signaling mediators, termed Smads, as regulators of vascular inflammation. These findings are beginning to establish a mechanistic scaffold with which to understand the cell-type specific function of Smads in the development of chronic inflammatory vascular disease states.
Feinberg
M W
MW
The Program in Cardiovascular Transcriptional Biology, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. mfeinberg@rics.bwh.harvard.edu
Jain
M K
MK
D000818:Animals; D050197:Atherosclerosis / Q000209:etiology* / Q000503:physiopathology; D006801:Humans; D008264:Macrophages / Q000502:physiology; D009000:Monocytes / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D015398:Signal Transduction; D051785:Smad Proteins / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology*; D053773:Transforming Growth Factor beta1; D014657:Vasculitis / Q000209:etiology* / Q000503:physiopathology
D051785:Smad Proteins; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1