Antiproliferative effects of immunosuppressant drugs on vascular smooth muscle cells: an additional advantage for attenuating transplant vasculopathy.
Coronary artery transplant vasculopathy (CATV) is the major cause of solid organ transplant failure. CATV is a vascular proliferative disease characterized by vascular smooth muscle cell (VSMC) activation obliterative arterial occlusion. Modalities used to treat conventional coronary artery disease are not applicable for most patients with CATV because of its chronic and extensive nature. The majority of drugs used in standard antirejection therapy are immunosuppressive and aim to suppress organ rejection by disabling the immune response. Since VSMCs are the major effector cells in the development of CATV, interruption of their activation and proliferation by immunosuppressive drugs represent a second line of attack with which to combat CATV. Fortunately, an unintended but advantageous side effect of many of these drugs is suppression of VSMC proliferation and consequential attenuation of the progression of CATV. This review summarizes the impact that the more commonly used immunosuppressives have on VSMC pathophysiology and examines the effects of some of the newer drugs that are specifically designed to attenuate VSMC activation. The risk of infection and malignancy associated with aggressive immunosuppressive therapy are a compelling impetus to develop drugs that directly and specifically impact the VSMC response to injury and may represent an important alternative or even a primary approach to attenuating CATV.
Autieri
Michael V
MV
Department of Physiology, Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA. mautieri@temple.edu
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002986:Clinical Trials as Topic; D006083:Graft Occlusion, Vascular / Q000473:pathology / Q000517:prevention & control*; D006084:Graft Rejection / Q000473:pathology / Q000517:prevention & control; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors
D007166:Immunosuppressive Agents; D011505:Protein-Tyrosine Kinases