Abstract:
:The mTOR (mechanistic target of rapamycin) is a master regulator of several crucial cellular processes, including protein synthesis, cellular growth, proliferation, autophagy, lysosomal function, and cell metabolism. mTOR interacts with specific adaptor proteins to form 2 multiprotein complexes, called mTORC1 (mTOR complex 1) and mTORC2 (mTOR complex 2). In the cardiovascular system, the mTOR pathway regulates both physiological and pathological processes in the heart. It is needed for embryonic cardiovascular development and for maintaining cardiac homeostasis in postnatal life. Studies involving mTOR loss-of-function models revealed that mTORC1 activation is indispensable for the development of adaptive cardiac hypertrophy in response to mechanical overload. mTORC2 is also required for normal cardiac physiology and ensures cardiomyocyte survival in response to pressure overload. However, partial genetic or pharmacological inhibition of mTORC1 reduces cardiac remodeling and heart failure in response to pressure overload and chronic myocardial infarction. In addition, mTORC1 blockade reduces cardiac derangements induced by genetic and metabolic disorders and has been reported to extend life span in mice. These studies suggest that pharmacological targeting of mTOR may represent a therapeutic strategy to confer cardioprotection, although clinical evidence in support of this notion is still scarce. This review summarizes and discusses the new evidence on the pathophysiological role of mTOR signaling in the cardiovascular system.
journal_name
Circ Resjournal_title
Circulation researchauthors
Sciarretta S,Forte M,Frati G,Sadoshima Jdoi
10.1161/CIRCRESAHA.117.311147subject
Has Abstractpub_date
2018-02-02 00:00:00pages
489-505issue
3eissn
0009-7330issn
1524-4571pii
CIRCRESAHA.117.311147journal_volume
122pub_type
杂志文章,评审abstract::Targeted expression of genetic material within the vascular endothelium is potentially a powerful tool for the investigation of endothelial cell (EC) biology. We developed, optimized, and characterized an efficient somatic transgenic model of EC-specific gene transfer. Rat carotid arteries were infused with adenovirus...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.77.3.475
更新日期:1995-09-01 00:00:00
abstract::Tyrosine kinase cascades may play a role in the hypoxic regulation of hypoxia-inducible factor (HIF)-1. We investigated the role of tyrosine kinase phosphorylation and of the Shc/Ras cascade on hypoxic HIF-1 stabilization. Exposure of human umbilical vein endothelial cells to hypoxia results in HIF protein stabilizati...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000024412.24491.ca
更新日期:2002-07-12 00:00:00
abstract::Previously, we have reported on the selective accumulation of an atrial-like myosin light chain-1 (ALC1) in different forms of human ventricular hypertrophy. The present study involves the determination of ALC1 content in a control group and in patients with aortic stenosis or insufficiency before and 56 +/- 23 months...
journal_title:Circulation research
pub_type: 临床试验,杂志文章
doi:10.1161/01.res.70.5.1035
更新日期:1992-05-01 00:00:00
abstract:RATIONALE:Hydrogen peroxide (H(2)O(2)) serves as a key endothelium-derived hyperpolarizing factor mediating flow-induced dilation in human coronary arterioles (HCAs). The precise mechanisms by which H(2)O(2) elicits smooth muscle hyperpolarization are not well understood. An important mode of action of H(2)O(2) involve...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.111.258871
更新日期:2012-02-03 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.64.6.1190
更新日期:1989-06-01 00:00:00
abstract::The structure of the mouse natriuretic peptide type-B (BNP) gene was determined by isolating and sequencing genomic clones. The mouse BNP gene was structurally similar to other natriuretic peptide genes and comprised three exons and two introns. Expression of the mouse BNP gene was found only in cardiac tissue as dete...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.72.5.984
更新日期:1993-05-01 00:00:00
abstract::Whereas numerous studies have investigated the role of prostacyclin and thromboxane A2 in the maintenance of coronary blood flow, most of these have focused on normal vessels. In the present investigation, we examined the prostaglandin- and thromboxane-synthesizing capacity of isolated coronary artery segments obtaine...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.57.2.223
更新日期:1985-08-01 00:00:00
abstract::Spatial and temporal organization of signal transduction is coordinated through the segregation of signaling enzymes in selected cellular compartments. This highly evolved regulatory mechanism ensures the activation of selected enzymes only in the vicinity of their target proteins. In this context, cAMP-responsive tri...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.111.262899
更新日期:2012-08-03 00:00:00
abstract::The purpose of this study was to develop an isolated tissue model in which arrhythmic activity could be generated in response to conditions encountered in ischemia followed by reperfusion, and in which intracellular recordings could be used to identify and study arrhythmogenic mechanisms. Isolated canine Purkinje fibe...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.56.2.184
更新日期:1985-02-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.114.302439
更新日期:2014-02-28 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.65.6.1547
更新日期:1989-12-01 00:00:00
abstract:RATIONALE:Significant progress has revealed transcriptional inputs that underlie regulation of artery and vein endothelial cell fates. However, little is known concerning genome-wide regulation of this process. Therefore, such studies are warranted to address this gap. OBJECTIVE:To identify and characterize artery- an...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.119.316075
更新日期:2020-03-27 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.67.6.1510
更新日期:1990-12-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh2101.098442
更新日期:2001-10-26 00:00:00
abstract::The paraoxonase (PON) gene cluster consists of the PON1, PON2, and PON3 genes, each of which can individually inhibit atherogenesis. To analyze the functions of the PON gene cluster (PC) in atherogenesis and plaque stability, human PC transgenic (Tg) mice were generated using bacterial artificial chromosome. The high-...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.108.192229
更新日期:2009-05-22 00:00:00
abstract::The kinetics of contractions and Ca(2+) transients are slowed in myocytes from failing hearts. The mechanisms accounting for these abnormalities remain unclear. Myocardial infarction (MI) was produced by ligation of the circumflex artery in rabbits. We used confocal microscopy to record spatially resolved Ca(2+) trans...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.87.11.1040
更新日期:2000-11-24 00:00:00
abstract::Topical application of sodium arachidonate (50-200 micrograms/ml) or bradykinin (0.1-10 micrograms/ml) on the brain surface of anesthetized cats caused dose-dependent cerebral arteriolar dilation. This dilation was blocked by 67-100% in the presence of superoxide dismutase and catalase. These enzymes did not affect th...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.55.3.295
更新日期:1984-09-01 00:00:00
abstract::To study whether atrial fibrillation might produce local changes in the atrium which could facilitate the tendency of this arrhythmia to become chronic and self-perpetuating, we compared the effect of atrial fibrillation, atrial pacing, and acute volume loading on the perfusion and oxygen consumption of the atrium in ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.51.2.205
更新日期:1982-08-01 00:00:00
abstract::Hearts from rabbits with 8-16 weeks of alloxan-diabetes were compared with hearts from normal rabbits to determine whether diabetic myocardium is more sensitive to ischemic injury. In isolated buffer-perfused hearts, left ventricular developed pressure, diastolic pressure, time to peak pressure (TTPP), time to half-ma...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.62.5.975
更新日期:1988-05-01 00:00:00
abstract::We performed experiments to determine whether or not acetylcholine exerts a prejunctional inhibitory effect on adrenergic neurotransmission in the human blood vessel wall. Rings of human greater saphenous veins were prepared 2 to 15 hours after death and mounted for isometric tension recording in organ chambers filled...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.49.2.337
更新日期:1981-08-01 00:00:00
abstract::An improved assay was used to investigate the effects of hypoxia or ischemia on interstitial fluid and coronary venous effluent levels of adenosine in isolated perfused nonworking rat hearts. The adenosine in 5- to 10-microliter samples of left ventricular epicardial surface transudates and coronary effluents was reac...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.60.2.177
更新日期:1987-02-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.115.307778
更新日期:2016-02-05 00:00:00
abstract::Animal and preliminary human studies of adult cell therapy following acute myocardial infarction have shown an overall improvement of cardiac function. Myocardial and vascular regeneration have been initially proposed as mechanisms of stem cell action. However, in many cases, the frequency of stem cell engraftment and...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.108.176826
更新日期:2008-11-21 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.res.38.6.2
更新日期:1976-06-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000126848.54740.4A
更新日期:2004-05-14 00:00:00
abstract:RATIONALE:Despite significant interest in bone marrow mononuclear cell (BMC) therapy for ischemic heart disease, current techniques have resulted in only modest benefits. However, selected patients have shown improvements after autologous BMC therapy, but the contributing factors are unclear. OBJECTIVE:The purpose of ...
journal_title:Circulation research
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1161/CIRCRESAHA.116.304710
更新日期:2015-01-02 00:00:00
abstract::Patients with diabetes mellitus have >2× the risk for developing heart failure (HF; HF with reduced ejection fraction and HF with preserved ejection fraction). Cardiovascular outcomes, hospitalization, and prognosis are worse for patients with diabetes mellitus relative to those without. Beyond the structural and func...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.118.311371
更新日期:2019-01-04 00:00:00
abstract::Experiments were performed to investigate whether balloon injury induces nitric oxide synthase activity in the blood vessel wall. Contractions to phenylephrine were compared in left carotid arteries of the rat, previously injured by balloon catheterization and excised either immediately (t = 0), 6, or 24 hours after t...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.71.2.331
更新日期:1992-08-01 00:00:00
abstract::Cytokine activation of vascular endothelial cells renders the hyperadhesiveness for neutrophils. During the processes of inflammation and atherosclerosis, the production of reactive oxygen species by neutrophils contributes to endothelial cell (EC) damage and injury. However, the precise mechanisms for neutrophil acti...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.88.4.422
更新日期:2001-03-02 00:00:00
abstract:RATIONALE:The epicardium contributes to the majority of nonmyocardial cells in the adult heart. Recent studies have reported that the epicardium is derived from Nkx2.5-positive progenitors and can differentiate into cardiomyocytes. Not much is known about the relation between the myocardial and epicardial lineage durin...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.203083
更新日期:2009-08-28 00:00:00