Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyclosporin A (CsA) is an immunosuppressant drug widely used in organ transplant recipients and people with autoimmune disorders. Long term treatment with CsA is associated with many side effects including hyperlipidemia and an increased risk of atherosclerosis. While its immunosuppressive effects are closely linked to its effects on T cell activation via the inhibition of the nuclear factor of activated T cells (NFAT) pathway, the precise mechanisms underlying its cardiovascular effects appear to involve multiple pathways additional to those relevant for immunosuppression. These include inhibition of calcineurin activity and intracellular cyclophilin peptidylprolyl isomerase and chaperone activities, inhibition of pro-inflammatory extracellular cyclophilin A, and NFAT-independent transcriptional effects. CsA demonstrates complex effects on lipoprotein metabolism and bile acid production, and affects endothelial cells, smooth muscle cells and macrophages, all of which are critical to the atherosclerotic process. Interpretation of the available data is hampered as many experimental models are used to study the effects of CsA in vivo and in vitro, leading to diverse and often contradictory findings. In this review we will describe the cellular mechanisms related to CsA-induced hyperlipidemia and atherosclerosis, with a focus on identifying pro-atherogenic pathways that are distinct from those relevant to its immunosuppressant effects. The potential of CsA analogues to avoid such sequelae will be discussed.
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PMID:Cyclosporin A and atherosclerosis--cellular pathways in atherogenesis. 2059 51

Cyclophilin A (CypA) is a ubiquitously distributed protein present both in intracellular and extracellular spaces. In atherosclerosis, various cells, including endothelial cells, monocytes, vascular smooth muscle cells and platelets, secrete CypA in response to excessive levels of reactive oxygen species. Atherosclerosis, a complicated disease, is the result of the interplay of different risk factors. Researchers have found that CypA links many risk factors, including hyperlipidemia, hypertension and diabetes, to atherosclerosis that develop into a vicious cycle. Furthermore, most studies have shown that secreted CypA participates in the developmental process of atherosclerosis via many important intracellular mechanisms. CypA can cause injury to and apoptosis of endothelial cells, leading to dysfunction of the endothelium. CypA may also induce the activation and migration of leukocytes, producing proinflammatory cytokines that promote inflammation in blood vessels. In addition, CypA can promote the proliferation of monocytes/macrophages and vascular smooth muscle cells, leading to the formation of foam cells and the remodelling of the vascular wall. Studies investigating the roles of CypA in atherosclerosis may provide new direction for preventive and interventional treatment strategies in atherosclerosis.
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PMID:Functions of cyclophilin A in atherosclerosis. 2394 Apr 49