Abstract:
RATIONALE:Depletion of medial smooth muscle cell (SMC) is a major pathological characteristic of abdominal aortic aneurysm (AAA), although the mechanism by which these cells are eliminated remains incompletely understood. We reasoned that necroptosis, a recently described form of necrosis mediated by receptor-interacting protein kinase 3 (RIP3), may contribute to AAA pathology through the induction of SMC death and the significant production of inflammatory cytokines. OBJECTIVE:To test the hypothesis that RIP3-mediated necroptosis is actively involved in aneurysm pathogenesis. METHODS AND RESULTS:RIP3 and RIP1 levels were found to be elevated in human AAAs, most noticeably in SMCs. Elevations of RIP3 and SMC necrosis were also observed in the elastase-induced mouse model of AAAs. Deletion of one or both copies of Rip3 prevented AAA formation. By transplanting Rip3(+/-) aortae to Rip3(+/+) mice, we demonstrated that reduced Rip3 expression in arterial wall was the primary cause of aneurysm resistance. In vitro, adenoviral overexpression of RIP3 was sufficient to trigger SMC necroptosis. Protein kinase C-delta contributed to tumor necrosis factor-α-induced SMC necroptosis by regulating Rip3 expression. Furthermore, Rip3 deficiency impaired tumor necrosis factor-α-induced inflammatory gene expression in aortic SMCs, which was at least in part because of attenuation of p65 Ser536 phosphorylation. In vivo, the lack of RIP3 diminished activation of p65 in SMCs, implicating a necrosis independent function of RIP3 in aneurysms. CONCLUSIONS:Enhanced RIP3 signaling in aneurysmal tissues contributes to AAA progression by causing SMC necroptosis, as well as stimulating vascular inflammation, and therefore may serve as a novel therapeutic target for AAA treatment.
journal_name
Circ Resjournal_title
Circulation researchauthors
Wang Q,Liu Z,Ren J,Morgan S,Assa C,Liu Bdoi
10.1161/CIRCRESAHA.116.304899subject
Has Abstractpub_date
2015-02-13 00:00:00pages
600-11issue
4eissn
0009-7330issn
1524-4571pii
CIRCRESAHA.116.304899journal_volume
116pub_type
杂志文章abstract::The identification of endothelium-derived relaxing factor as nitric oxide (NO) dramatically altered the course of vascular biology, as well as other biomedical disciplines. The ubiquity of this natural product of cell metabolism and the complexity of its biochemistry provide a rich source of molecular mediators of phe...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.113.301577
更新日期:2013-07-05 00:00:00
abstract::Diabetes mellitus has profound adverse effects on vascular and, in particular, endothelial function. Although pressure-induced constriction ("myogenic tone") is a major contributor to the regulation of blood flow, little is known about the effects of diabetes on this response. Diabetes has been shown to diminish the d...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.81.6.996
更新日期:1997-12-01 00:00:00
abstract::Recent evidence shows that circulating granulocytes play an important role in capillary stasis and tissue injury. We investigated two aspects of the problem in a Wiggers hemorrhagic shock model of the rat: the survival rate and the microvascular no-reflow phenomenon. A conventional group of rats with normal blood cell...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.63.2.437
更新日期:1988-08-01 00:00:00
abstract::Many indices have been proposed to describee the diastolic pressure-volume curve mathematically and permit quantification of the elastic properties of the myocardium itself in hopes that changes in the muscle caused by disease would b.e reflected in the diastolic pressure-volume curve. To date, none of the proposed in...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.39.6.772
更新日期:1976-12-01 00:00:00
abstract::Structural remodeling of the ventricular wall is a key determinant of clinical outcome in heart disease. Such remodeling involves the production and destruction of extracellular matrix proteins, cell proliferation and migration, and apoptotic and necrotic cell death. Cardiac fibroblasts are crucially involved in these...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.res.0000046452.67724.b8
更新日期:2002-12-13 00:00:00
abstract::Adenosine, a vasodilator metabolite, is often produced in tissues where the demand for oxygen exceeds the supply. We have recently demonstrated in isolated cannulated arterioles that adenosine and its metabolite, inosine, can also cause vasoconstriction by stimulation of mast cells. Secondary release of histamine and ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.78.4.627
更新日期:1996-04-01 00:00:00
abstract::The cardiac troponin T (TnT) I79N mutation has been linked to familial hypertrophic cardiomyopathy and high incidence of sudden death, despite causing little or no cardiac hypertrophy in patients. Transgenic mice expressing mutant human TnT (I79N-Tg) have increased cardiac contractility, but no ventricular hypertrophy...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000059562.91384.1A
更新日期:2003-03-07 00:00:00
abstract::Rho regulates various cell functions, including cell morphology and motility. However, the functional role of Rho on the signaling pathway in myocardial cells (MCs) is unknown. In the present study, we attempted to explore the mode of Rho action for c-fos gene expression in MCs. Expression of the c-fos promoter/enhanc...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.81.5.672
更新日期:1997-11-01 00:00:00
abstract::The introduction of statins ≈ 30 years ago ushered in the era of lipid lowering as the most effective way to reduce risk of atherosclerotic cardiovascular disease. Nonetheless, residual risk remains high, and statin intolerance is frequently encountered in clinical practice. After a long dry period, the field of thera...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.115.306471
更新日期:2016-02-19 00:00:00
abstract::Trimetazidine is a clinically effective antianginal agent that has no negative inotropic or vasodilator properties. Although it is thought to have direct cytoprotective actions on the myocardium, the mechanism(s) by which this occurs is as yet undefined. In this study, we determined what effects trimetazidine has on b...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.86.5.580
更新日期:2000-03-17 00:00:00
abstract::To determine whether opioid receptors (ORs) are involved in the delayed cardioprotection of ischemic preconditioning (IP), the effect of severe metabolic inhibition (MI) with a glucose-free buffer that contained sodium cyanide and 2-deoxy-D-glucose on the viability of isolated rat ventricular myocytes was first determ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.84.12.1388
更新日期:1999-06-25 00:00:00
abstract::Although diabetes is recognized as a potent and prevalent risk factor for ischemic heart disease, less is known as to whether diabetes causes an altered cardiac phenotype independent of coronary atherosclerosis. Left ventricular systolic and diastolic dysfunction, left ventricular hypertrophy, and alterations in the c...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.RES.0000207406.94146.c2
更新日期:2006-03-17 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 elucidate the mechanisms responsible for the increase in alpha 1-adrenergic receptors during ischemia in vivo, we developed a procedure for measuring alpha 1-adrenergic receptors in isolated, calcium-tolerant adult canine myocytes. Specific [3H]prazosin binding was rapid, saturable, reversible, and demonstrated the...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.61.5.735
更新日期:1987-11-01 00:00:00
abstract::The epicardium, the tissue layer covering the cardiac muscle (myocardium), develops from the proepicardium, a mass of coelomic progenitors located at the venous pole of the embryonic heart. Proepicardium cells attach to and spread over the myocardium to form the primitive epicardial epithelium. The epicardium subseque...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.111.245589
更新日期:2011-12-09 00:00:00
abstract::Angiotensin II (Ang II) increases renal sympathetic nerve activity in anesthetized mice before and after ganglionic blockade, suggesting that Ang II may directly activate postganglionic sympathetic neurons. The present study directly tested this hypothesis in vitro. Neurons were dissociated from aortic-renal and celia...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh0801.089542
更新日期:2001-04-27 00:00:00
abstract::Vascular endothelial growth factor (VEGF) expression is upregulated by hypoxia-inducible factor-1 (HIF-1) in ischemic tissues and growing tumors. Normally, HIF-1 activity depends on the amount of HIF-1alpha subunit, which is tightly regulated by the oxygen tension. In the myocardium, VEGF expression has been shown to ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh0202.104923
更新日期:2002-02-08 00:00:00
abstract::Atherosclerosis is considered to be an inflammatory disease. Tissue factor (TF), a prothrombotic molecule expressed by various cell types within atherosclerotic plaques, is thought to play an essential role in thrombus formation after atherosclerotic plaque rupture. Recent studies suggest that the antiinflammatory cyt...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000177893.24574.13
更新日期:2005-08-19 00:00:00
abstract::Recent pharmacological studies have shown that perivascular nerves can influence the development and function of vascular endothelial cells (ECs). However, morphological studies have not yet been carried out to investigate whether these functional changes are associated with changes in vasoactive substances in ECs. We...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.79.2.317
更新日期:1996-08-01 00:00:00
abstract::The extracellular and intracellular potassium (K+) activities of isolated superfused rabbit atrial muscle were measured using K+-sensitive liquid ion exchanger microelectrodes. When the pH of the bathing medium was decreased from 7.5 to 6.8, intracellular K+ activity fell and extracellular K+ activity rose from a mean...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.39.5.678
更新日期:1976-11-01 00:00:00
abstract:RATIONALE:The cardiac inwardly rectifying K(+) current (I(K1)) plays a critical role in modulating excitability by setting the resting membrane potential and shaping phase 3 of the cardiac action potential. OBJECTIVE:This study aims to analyze the effects of nitric oxide (NO) on human atrial I(K1) and on Kir2.1 channe...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.197558
更新日期:2009-08-14 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2014-05-23 00:00:00
abstract:RATIONALE:Circulating progenitor cells (CPCs) mobilize in response to ischemic injury, but their predictive value remains unknown in acute coronary syndrome (ACS). OBJECTIVE:We aimed to investigate the number of CPCs in ACS compared with those with stable coronary artery disease (CAD), relationship between bone marrow...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.118.312821
更新日期:2018-05-25 00:00:00
abstract:RATIONALE:Patients with chronic kidney disease (CKD) develop hyperhomocysteinemia and have a higher cardiovascular mortality than those without hyperhomocysteinemia by 10-fold. OBJECTIVE:We investigated monocyte differentiation in human CKD and cardiovascular disease (CVD). METHODS AND RESULTS:We identified CD40 as a...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.308750
更新日期:2016-11-11 00:00:00
abstract:RATIONALE:We have shown recently that particulate (pGC) and soluble guanylyl (sGC) cyclases synthesize cGMP in different compartments in adult rat ventricular myocytes (ARVMs). OBJECTIVE:We hypothesized that cGMP-dependent protein kinase (PKG) exerts a feedback control on cGMP concentration contributing to its intrace...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.110.226712
更新日期:2010-11-12 00:00:00
abstract::The goals of this article were (1) to identify cell surface proteins whose expression was regulated by diabetes and (2) to assess their contribution to diabetic complications. We purified heat shock protein 90alpha (Hsp90alpha) from the membrane fraction of high glucose-treated endothelial cells (ECs) as a binding par...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000124979.46214.E3
更新日期:2004-04-16 00:00:00
abstract::Oxidative stress has been suggested to potentiate atherogenesis. However, studies that have investigated the effect of antioxidants on atherosclerosis showed inconsistent results, ie, atherosclerosis was either retarded or not changed by dietary antioxidants. This report directly examined the effect of overexpressing ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000149564.49410.0d
更新日期:2004-11-26 00:00:00
abstract::Cellular Ca2+ regulation is abnormal in diseased hearts. We designed this study to assess the role of the Na(+)-Ca2+ exchanger in excitation-contraction coupling in surviving myocardium of the infarcted heart. We measured cellular contractions and whole-cell currents in single left ventricular myocytes isolated from t...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.81.6.1083
更新日期:1997-12-01 00:00:00
abstract::Controversy exists whether positive end-expiratory pressure (PEEP) ventilation lowers cardiac output by reducing left ventricular preload, or by a combination of mechanisms. Sixteen open-chest dogs were instrumented for measurement of left and right ventricular pressure, aortic flow, and left ventricular dimensions. W...
journal_title:Circulation research
pub_type: 杂志文章,收录出版
doi:10.1161/01.res.49.4.1017
更新日期:1981-10-01 00:00:00
abstract::In 26 Wistar rats with surface glomeruli, the determinants of glomerular ultrafiltration and peritubular capillary uptake of proximal reabsorbate were studied before and during intravenous infusions of norepinephrine or angiotensin II. Regardless of whether renal perfusion pressure (AP) was permitted to increase, both...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.37.1.101
更新日期:1975-07-01 00:00:00