Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42345 (mTOR)
 26,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The incidence, pathogenesis, consequences and treatment of mammalian target of rapamycin (mTOR) inhibitor dyslipidemia are not well described. We conducted a systematic review of randomized controlled trials reporting cholesterol and triglycerides in mTOR versus non-mTOR inhibitor immunosuppressive treatment regimens in kidney transplant recipients. All but one of 17 trials reported higher levels of cholesterol and triglycerides, or an increased prevalence of treatment with lipid-lowering agents. Approximately 60% of mTOR inhibitor-treated patients received lipid-lowering agents (2-fold higher than controls). There appeared to be little difference between dyslipidemias caused by sirolimus (14 trials) versus everolimus (3 trials). It was difficult to determine the extent to which declines in lipids over time posttransplant were due to lipid-lowering therapy, changes in doses and/or discontinuations of mTOR inhibitors. From the four trials that measured lipoproteins, it appeared that at least some of the increase in total cholesterol with mTOR inhibitors was due to increased low-density lipoprotein cholesterol. What direct or indirect effects mTOR inhibitors have on atherosclerotic cardiovascular disease in kidney transplant patients are unknown. However, in the absence of the necessary clinical trials, dyslipidemia should be managed, as it would be in nontransplant patients at high risk for cardiovascular disease.
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PMID:Mammalian target of rapamycin inhibitor dyslipidemia in kidney transplant recipients. 1851 Jun 33

Hypertension in kidney transplant recipients is a major "traditional" risk factor for atherosclerotic cardiovascular disease. Importantly, atherosclerotic cardiovascular disease is the leading cause of premature death and a major factor in death-censored graft failure in transplant recipients. The blood pressure achieved after transplant is related inversely to postoperative glomerular filtration rate (GFR), with many patients experiencing a significant improvement in blood pressure control with fewer medications within months of surgery. However, the benefits of improved GFR and fluid status may be affected by the immunosuppression regimen. Immunosuppressive agents affect hypertension through a variety of mechanisms, including catechol- and endothelin-induced vasoconstriction, abrogation of nitric oxide-induced vasodilatation, and sodium retention. Most notable is the role of calcineurin inhibitors in promoting hypertension, cyclosporine more so than tacrolimus. Additionally, the combination of calcineurin- and mammalian target of rapamycin (mTOR)-inhibitor therapy is synergistically nephrotoxic and promotes hypertension, whereas steroid withdrawal and minimization strategies seem to have little or no impact on hypertension. Other important causes of hypertension after transplant, beyond a progressive decrease in GFR, include transplant renal artery stenosis and sequelae of antibody-mediated rejection. Calcium channel blockers may be the most useful medication for mitigating calcineurin inhibitor-induced vasoconstriction, and use of such agents may be associated with improvements in GFR. Use of inhibitors of the renin-angiotensin system, such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, remains an attractive strategy for many transplant recipients, although some recipients may have significant adverse effects associated with these medications, including decreased GFR, hyperkalemia, and anemia. In conclusion, hypertension control affects both patient and long-term transplant survival, and its best management requires careful analysis of causes and close monitoring of therapies.
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PMID:Hypertension after kidney transplant. 2125 43

AMP-activated protein kinase (AMPK) plays a critical role both in sensing and regulating cellular energy state. In experimental animals, its activation has been shown to reduce the risk of obesity and diabetes-related co-morbidities such as insulin resistance, the metabolic syndrome and atherosclerotic cardiovascular disease. However, in humans, AMPK activation alone often does not completely resolve these conditions. Thus, an improved understanding of AMPK action and regulation in metabolic and other diseases is needed. Herein, we provide a brief description of the enzymatic regulation of AMPK and review its role in maintaining energy homeostasis. We then discuss tissue-specific actions of AMPK that become distorted during such conditions as obesity, type 2 diabetes and certain cancers. Finally, we explore recent findings regarding the interactions of AMPK with mammalian target of rapamycin complex 1 and the lysosome and discuss how changes in these relationships during overnutrition may lead to AMPK dysfunction. A more thorough understanding of AMPK's molecular interactions during diseases of overnutrition may provide key insights for the development of AMPK-based combinatorial treatments for metabolic disease.
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PMID:Unraveling the actions of AMP-activated protein kinase in metabolic diseases: Systemic to molecular insights. 2708 72