Abstract:
:The aging population is increasing in developed countries. Because the incidence of cardiac disease increases dramatically with age, it is important to understand the molecular mechanisms through which the heart becomes either more or less susceptible to stress. Cardiac aging is characterized by the presence of hypertrophy, fibrosis, and accumulation of misfolded proteins and dysfunctional mitochondria. Macroautophagy (hereafter referred to as autophagy) is a lysosome-dependent bulk degradation mechanism that is essential for intracellular protein and organelle quality control. Autophagy and autophagic flux are generally decreased in aging hearts, and murine autophagy loss-of-function models develop exacerbated cardiac dysfunction that is accompanied by the accumulation of misfolded proteins and dysfunctional organelles. On the contrary, stimulation of autophagy generally improves cardiac function in mouse models of protein aggregation by removing accumulated misfolded proteins, dysfunctional mitochondria, and damaged DNA, thereby improving the overall cellular environment and alleviating aging-associated pathology in the heart. Increasing lines of evidence suggest that autophagy is required for many mechanisms that mediate lifespan extension, such as caloric restriction, in various organisms. These results raise the exciting possibility that autophagy may play an important role in combating the adverse effects of aging in the heart. In this review, we discuss the role of autophagy in the heart during aging, how autophagy alleviates age-dependent changes in the heart, and how the level of autophagy in the aging heart can be restored.
journal_name
Circ Resjournal_title
Circulation researchauthors
Shirakabe A,Ikeda Y,Sciarretta S,Zablocki DK,Sadoshima Jdoi
10.1161/CIRCRESAHA.116.307474subject
Has Abstractpub_date
2016-05-13 00:00:00pages
1563-76issue
10eissn
0009-7330issn
1524-4571pii
CIRCRESAHA.116.307474journal_volume
118pub_type
杂志文章,评审abstract:BACKGROUND:Myocyte contractile dysfunction occurs in pathological remodeling in association with abnormalities in calcium regulation. Mice with cardiac myocyte-specific overexpression of Galphaq develop progressive left ventricular failure associated with myocyte contractile dysfunction and calcium dysregulation. OBJE...
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abstract::To gain some insight into inotropic mechanisms, we compared the effects of several classes of inotropic interventions on the isometric twitch and force-velocity properties of isolated rabbit myocardium. Postextrasystolic potentiation was chosen as one of the interventions in the belief that its onset is so rapid that ...
journal_title:Circulation research
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doi:10.1161/01.res.65.5.1161
更新日期:1989-11-01 00:00:00
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更新日期:2005-11-11 00:00:00
abstract::The purpose of this study was to explore the changes in fetal blood volume that occur after fetal hemorrhage. Fifteen unanesthetized, chronically catheterized fetal sheep averaging 130 +/- 3 (SD) days gestation were studied 4 to 6 (average 5) days after catheter implantation. The fetuses were hemorrhaged by continuous...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.52.6.730
更新日期:1983-06-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.71.2.460
更新日期:1992-08-01 00:00:00
abstract::The effects of digoxin on monovalent cation active transport were determined in cardiac tissue obtained from dogs given inotropic, toxic, or lethal doses of digoxin. In hemodynamically monitored dogs, active uptake of the K+ analogue Rb+ was determined in vitro in a control myocardial biopsy, and then in serial biopsi...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.44.1.23
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abstract::After myocardial infarction (MI), the noninfarcted myocardium undergoes significant hypertrophy as part of the post-MI structural remodeling. Electrophysiological changes associated with the hypertrophied remodeled myocardium may play a key role in arrhythmia generation in the post-MI heart. We investigated the cellul...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.79.3.461
更新日期:1996-09-01 00:00:00
abstract::The mechanism of adenosine-induced inhibition of Ca2+ currents was studied by recording single-channel Ca2+ currents from cell-attached patches on isolated guinea pig ventricular cells with pipettes containing 50 or 100 mM Ba2+. Numerous 100-msec depolarization steps were applied repetitively at 2 Hz from the resting ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.67.5.1134
更新日期:1990-11-01 00:00:00
abstract::The role of the central nervous system in the mechanism(s) involved in acute carotid baroreflex resetting was studied in six conscious, chronically instrumented, aortic-denervated dogs. Dogs were prepared for reversible vascular isolation of the carotid sinuses. Acute baroreflex resetting was induced by holding the le...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.65.1.63
更新日期:1989-07-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.309322
更新日期:2017-01-20 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.74.3.416
更新日期:1994-03-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000134631.75684.4A
更新日期:2004-07-09 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.107.157271
更新日期:2007-08-31 00:00:00
abstract::Shear stress caused by the frictional forces of a fluid moving over a cell monolayer is an important regulator of gene expression. In this study, we investigated the effect of shear stress on angiotensin-converting enzyme (ACE) expression and promoter activity in vitro and on local vascular ACE activity in vivo. ACE a...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.80.3.312
更新日期:1997-03-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000216595.15868.55
更新日期:2006-04-14 00:00:00
abstract:RATIONALE:In normal and diseased vascular smooth muscle (SM), the RhoA pathway, which is activated by multiple agonists through G protein-coupled receptors (GPCRs), plays a central role in regulating basal tone and peripheral resistance. This occurs through inhibition of myosin light chain phosphatase, leading to incre...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.111.248898
更新日期:2011-10-14 00:00:00
abstract:RATIONALE:Microparticles are cell-derived membrane vesicles, relevant to a range of biological responses and known to be elevated in cardiovascular disease. OBJECTIVE:To investigate microparticle release during cardiac stress and how this response differs in those with vascular disease. METHODS AND RESULTS:We measure...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.114.301904
更新日期:2014-01-03 00:00:00
abstract::Ventricular repolarization was analyzed by measuring epicardial potential distributions in intact dogs with single or multiple ectopic foci and a minimum at the terminal site(s) of excitation. During the latter half of the T wave the distributions became more complex, and two maxima evolved from the initial one at eac...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.39.4.475
更新日期:1976-10-01 00:00:00
abstract:RATIONALE:A hallmark of chronic inflammatory disorders is persistence of proinflammatory macrophages in diseased tissues. In atherosclerosis, this is associated with dyslipidemia and oxidative stress, but mechanisms linking these phenomena to macrophage activation remain incompletely understood. OBJECTIVE:To investiga...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.119.315833
更新日期:2019-12-06 00:00:00
abstract:RATIONALE:The recent discovery of meningeal lymphatics in mammals is reshaping our understanding of fluid homeostasis and cellular waste management in the brain, but visualization and experimental analysis of these vessels is challenging in mammals. Although the optical clarity and experimental advantages of zebrafish ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.120.317372
更新日期:2021-01-08 00:00:00
abstract::Patients with severe heart failure are at high risk of sudden cardiac death. In the majority of these patients, sudden cardiac death is thought to be due to ventricular tachyarrhythmias. Alterations of the electric properties of single myocytes in heart failure may favor the occurrence of ventricular arrhythmias in th...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.82.11.1206
更新日期:1998-06-15 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.67.1.193
更新日期:1990-07-01 00:00:00
abstract::The cellular basis of reactive oxygen intermediate-induced arrhythmias was investigated in isolated rabbit ventricular cells using the whole-cell voltage- and current-clamp techniques. Singlet oxygen and superoxide were generated by the photoactivation of rose bengal. Single ventricular cells exposed to rose bengal (1...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.68.2.319
更新日期:1991-02-01 00:00:00
abstract::By use of gene targeting and/or transgenesis, it is now possible to make defined changes in genes whose functions underlie mammalian cardiovascular function. Because of technical and economic considerations, these experiments are largely confined to the mouse. Genetic modification of the loci responsible for aspects o...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.res.82.4.407
更新日期:1998-03-09 00:00:00
abstract::Mitral regurgitation (MR) causes ventricular dilation, a blunted myocardial force-frequency relation, and increased crossbridge force-time integral (FTI). The mechanism of FTI increase was investigated using sinusoidal length perturbation analysis to compare crossbridge function in skinned left ventricular (LV) epicar...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh0102.103221
更新日期:2002-01-11 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.107.156901
更新日期:2007-07-20 00:00:00
abstract::Vascular disease often involves vessel hypertrophy with underlying cellular hypertrophy or hyperplasia. Experimental diabetes stimulates hypertrophy of the rat mesenteric vasculature, and we investigated the hypothesis that this hypertrophy is associated with activation of Na(+)-H(+) exchange (NHE) activity. We measur...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.87.12.1133
更新日期:2000-12-08 00:00:00
abstract::Increased glomerular capillary hydrostatic pressure (PGC) is an important hemodynamic determinant of glomerular injury, but the molecular events responsible for this association are poorly understood. PGC is normal in spontaneously hypertensive rats (SHR), but uninephrectomy leads to an increase in PGC and accelerated...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.75.5.844
更新日期:1994-11-01 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:RATIONALE:Mechanical stress plays an important role in proliferation of venous smooth muscle cells (SMCs) in neointima, a process of formation that contributes to failure of vein grafts. However, it is unknown what intracellular growth signal leads to proliferation of venous SMCs. OBJECTIVE:The objective of this study...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.110.222588
更新日期:2010-11-12 00:00:00