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)

Cardiovascular diseases (CVD) are the leading cause of mortality in renal transplant recipients. Various traditional and unconventional cardiovascular risk factors are potentiated by the adverse effects of immunosuppressive drugs. The mammalian target of rapamycin (mTOR) inhibitors have shown cardioprotective effects in experimental studies, but their influence on CVD in renal transplantation is unclear. The study included 115 kidney transplant recipients treated with mTOR inhibitors with steroids. A group of 38 patients received additionally small doses of calcineurin inhibitor. The control group consisted of 58 kidney transplant recipients randomly chosen among the population of patients transplanted at the same time, who received a calcineurin inhibitor, mycophenolate mofetil or sodium plus steroids. No differences in age, gender, duration of pretransplantat dialysis, time after transplantation, body mass index or glycated hemoglobin existed between the groups. Blood pressure and number of antihypertensive agents, high-density lipoprotein cholesterol, and uric acid levels were similar. The prevalence of diabetic, ischemic, or hypertensive nephropathy as the reason for end-stage renal disease was similar (P=.08). The study group showed higher mean values of total cholesterol (249 vs 204.6 mg/dL; P<.0001) and low-density lipoprotein 136.5 vs 117.7 mg/dL; (P=.015), as well as median values of triglycerides (202 vs 142 mg/dL; P<.0001) and proteinuria (P=.0002). mean estimated glomerular filtration rate was lower in the study group (42.9 vs 51.9 mL/min; P=.0003). Posttransplant diabetes appeared in 38% of the study group compared to 20% of the controls (P=.08). The incidence of coronary artery disease was higher among patients treated with mTOR inhibitors (P=.04). CVD, defined as myocardial infarction, percutaneous coronary intervention, stroke, aortic aneurysm, pulmonary thromboembolism, sudden cardiac death appeared in 26 study group compared with four control patients (P=.24). The risk of any CVD was not significantly higher among patients receiving mTOR inhibitors hazard ratio 1.94; 95% confidence interval 0.83-4.52). In conclusion, no correlation was observed between the duration of mTOR therapy and CVD.
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PMID:Cardiovascular risk in kidney transplant recipients receiving mammalian target of rapamycin inhibitors. 2199 2

Continuous activation of angiotensin II (Ang II) induces renal vascular endothelial dysfunction, inflammation and oxidative stress, all of which may contribute to renal damage. MicroRNAs (miRs/miRNAs) play a crucial regulatory role in the pathogenesis of hypertensive nephropathy (HN). The present study aimed to assess the differential expression profiles of potential candidate genes involved in Ang II-induced rat renal artery endothelial cell (RRAEC) dysfunction and explore their possible functions. In the present study, the changes in energy metabolism and autophagy function in RRAECs were evaluated using the Seahorse XF Glycolysis Stress Test and dansylcadaverine/transmission electron microscopy following exposure to Ang II. Subsequently, mRNA-miRNA sequencing experiments were performed to determine the differential expression profiles of mRNAs and miRNAs. Integrated bioinformatics analysis was applied to further explore the molecular mechanisms of Ang II on endothelial injury induced by Ang II. The present data supported the notion that Ang II upregulated glycolysis levels and promoted autophagy activation in RRAECs. The sequencing data demonstrated that 443 mRNAs and 58 miRNAs were differentially expressed (DE) in response to Ang II exposure, where 66 mRNAs and 55 miRNAs were upregulated, while 377 mRNAs and 3 miRNAs were downregulated (fold change >1.5 or <0.67; P<0.05). Functional analysis indicated that DE mRNA and DE miRNA target genes were mainly associated with cell metabolism (metabolic pathways), differentiation (Th1 and Th2 cell differentiation), autophagy (autophagy-animal and autophagy-other) and repair (RNA-repair). To the best of the authors' knowledge, this is the first report on mRNA-miRNA integrated profiles of Ang II-induced RRAECs. The present results provided evidence suggesting that the miRNA-mediated effect on the 'mTOR signaling pathway' might play a role in Ang II-induced RRAEC injury by driving glycolysis and autophagy activation. Targeting miRNAs and their associated pathways may provide valuable insight into the clinical management of HN and may improve patient outcome.
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PMID:MicroRNA and mRNA analysis of angiotensin II-induced renal artery endothelial cell dysfunction. 3234 37