Potential role of proliferation signal inhibitors on atherosclerosis in renal transplant patients.
Over the last decade, there has been a decrease in acute graft rejection rates following renal transplantation; however, this has not corresponded with an improvement in long-term outcomes of transplantation. One of the major causes of long-term morbidity and mortality in renal transplant recipients is cardiovascular disease. Immunosuppressive regimens, especially those including steroids and calcineurin inhibitors, have a negative role in the induction of cardiovascular risk factors. The proliferation signal inhibitors (PSIs)/mammalian target of rapamycin (mTOR) inhibitors sirolimus and everolimus have shown considerable promise in reducing acute rejection in renal transplant recipients. Although PSIs are associated with an increase in hyperlipidaemia (hypercholesterolaemia and hypertriglyceridaemia), which is a major risk factor for atherosclerosis and associated cardiovascular disease, recent studies with sirolimus have demonstrated protection from atheroma progression in hyperlipidaemic apolipoprotein E-deficient mice. Here, we summarize the results of pre-clinical and clinical studies with sirolimus and everolimus, with particular emphasis on the beneficial and adverse effects that these drugs exert on the cardiovascular system, and the underlying molecular mechanisms.
Andrés
Vicente
V
Vascular Biology Laboratory, Department of Molecular and Cellular Pathology and Therapy, Instituto de Biomedicina de Valencia, Spain.
Castro
Claudia
C
Campistol
Josep M
JM
D050197:Atherosclerosis / Q000209:etiology*; D049109:Cell Proliferation / Q000187:drug effects*; D000068338:Everolimus; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016030:Kidney Transplantation; D011183:Postoperative Complications / Q000209:etiology*; D011494:Protein Kinases / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases
D007166:Immunosuppressive Agents; D000068338:Everolimus; D011494:Protein Kinases; C546842:MTOR protein, human; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus