title: Inhibition of the mTOR pathway: a possible protective role in coronary artery disease.
abstract: The main approach to obesity and type-II diabetes is to unravel the mechanisms involved in nutrient absorption and fuel allocation. In conditions of over-nutrition, cells must cope with a multitude of extracellular signals generated by changes in nutrient load, hormonal milieu, adverse cytokine/adipokine profile, and apoptosis/anti-apoptosis processes. To date studies have demonstrate that among all nutrients, lipids and carbohydrates play a major regulatory role in the gene transcription of glycolytic and lipogenic enzymes, insulin, and adipokines. These nutrients mainly exert their effects through the gene expression of sterol responsive binding protein 1 and 2 (SREBP) and the mammalian target of rapamycin (mTOR). Excess of adipose tissue is known to confer a significantly higher risk of coronary artery disease. Administration of rapamycin effectively attenuated inflammation, inhibited progression, and enhanced stability of atherosclerotic plaques in animal models. Herein we discuss the mTOR pathway and the molecular mechanisms of mTOR inhibitors, hypothesizing a possible protective role in atherosclerosis, taking into account also previous clinical studies emphasizing their opposite role.
authors.affiliation: Department of Clinical Medicine and Surgery, Federico II University Medical School of Naples, Italy. tarantin@unina.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tarantino
authors.forename: Domenico
authors.initials: D
authors.lastname: Capone
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D003324:Coronary Artery Disease / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism* / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism; D006801:Humans; D009765:Obesity / Q000150:complications / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus