Accelerated arteriosclerosis after transplantation: the possible role of calcium channel blockers.
The major factor limiting the long-term success of cardiac transplantation is the development of accelerated arteriosclerosis that occurs in the coronary arteries of the cardiac allograft. Transplant arteriosclerosis is characterized by diffuse, uniform, concentric narrowing of the artery by a proliferative, fibrocellular intima. The etiology of transplant arteriosclerosis is thought to be immune-mediated, and endothelial cells, smooth muscle cells, and inflammatory cells participate in the progression. Based on data derived from studies of conventional atherosclerosis, in which calcium channel blockers (CCBs) have demonstrated beneficial effects, preliminary studies designed to determine if CCBs might affect transplant arteriosclerosis similarly have been performed in animal models as well as in a limited number of cardiac transplant patients. Amlodipine suppressed transplant arteriosclerosis in one animal study, while diltiazem preserved vasodilatory responses in another animal study. Small prospective trials and retrospective studies in humans have shown that CCBs have a favorable effect on the development of transplant arteriosclerosis. While no work has been directed specifically at determining the mechanisms by which CCBs might prevent transplant arteriosclerosis, there are several likely candidates. These include preservation of endothelial function, suppression of smooth muscle cell migration and proliferation, production of extracellular matrix, and regulation of lipid metabolism and certain components of the immune system.
Atkinson
J B
JB
Department of Pathology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
D017311:Amlodipine / Q000627:therapeutic use*; D000818:Animals; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D003324:Coronary Artery Disease / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology; D004110:Diltiazem / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans
D002121:Calcium Channel Blockers; D017311:Amlodipine; D004110:Diltiazem