Understanding the role of transforming growth factor-beta1 in intimal thickening after vascular injury.
Intimal thickening is the most important cause of in-stent restenosis. The pathology of intimal thickening is attributable to a local inflammatory response after vascular injury which results in the production of cytokines. Transforming growth factor-beta1 (TGF-beta1) is a profibrotic cytokine that is involved in the induction of intimal thickening. Up-regulation of TGF-beta1 after arterial injury results in the activation of various downstream pathways which stimulate the proliferation and migration of vascular smooth muscle cells, as well as the production of local extracellular matrix proteins. Recent evidence suggests that antagonizing TGF-beta1 activity with direct or indirect inhibitors may attenuate or prevent intimal thickening. Additionally, TGF-beta1 synthesis, activation and downstream regulation may also serve as significant sources of treatment. This review attempts to show the role of TGF-beta1 in the pathology of intimal thickening and underlines the importance of TGF-beta1 as a target for therapy.
Khan
Razi
R
Department of Internal Medicine, University of Western Ontario, Suite 1604, 1265 Richmond St. North, London, Ontario, Canada N6A 3M1. razi.khan@gmail.com
Agrotis
Alex
A
Bobik
Alex
A
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D049109:Cell Proliferation; D023903:Coronary Restenosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053782:Transforming Growth Factor beta3 / Q000627:therapeutic use; D017539:Tunica Intima / Q000293:injuries* / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology*; D062367:ortho-Aminobenzoates / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016326:Extracellular Matrix Proteins; D053773:Transforming Growth Factor beta1; D053782:Transforming Growth Factor beta3; D062367:ortho-Aminobenzoates; C012293:tranilast