Abstract:
RATIONALE:Disruption of endothelial barrier function and neutrophil-mediated injury are two major mechanisms underlying the pathophysiology of sepsis-induced acute lung injury (ALI). Recently we reported that endotoxin induced activation of RhoA in mice lungs that led to the disruption of endothelial barrier and lung edema formation; however, the molecular mechanism of this phenomenon remained unknown. OBJECTIVE:We reasoned that LIMK1, which participates in the regulation of endothelial cell contractility and is activated by RhoA/Rho kinase pathway, could mediate RhoA-dependent disruption of endothelial barrier function in mouse lungs during ALI. And if that is the case, then attenuation of endothelial cell contractility by downregulating LIMK1 may lead to the enhancement of endothelial barrier function, which could protect mice from endotoxin-induced ALI. METHODS AND RESULTS:Here we report that LIMK1 deficiency in mice significantly reduced mortality induced by endotoxin. Data showed that lung edema formation, lung microvascular permeability, and neutrophil infiltration into the lungs were suppressed in limk1(-/-) mice. CONCLUSIONS:We identified that improvement of endothelial barrier function along with impaired neutrophil chemotaxis were the underlying mechanisms that reduced severity of ALI in limk1(-/-) mice, pointing to a new therapeutic target for diseases associated with acute inflammation of the lungs.
journal_name
Circ Resjournal_title
Circulation researchauthors
Gorovoy M,Han J,Pan H,Welch E,Neamu R,Jia Z,Predescu D,Vogel S,Minshall RD,Ye RD,Malik AB,Voyno-Yasenetskaya Tdoi
10.1161/CIRCRESAHA.109.195883subject
Has Abstractpub_date
2009-09-11 00:00:00pages
549-56issue
6eissn
0009-7330issn
1524-4571pii
CIRCRESAHA.109.195883journal_volume
105pub_type
杂志文章abstract::To evaluate the degree and lateral extent of dysfunction in nonischemic myocardium adjacent to ischemic muscle, we measured systolic wall thickening with sonomicrometers during circumflex coronary occlusion in 12 anesthetized, open-chest dogs. The locations of the wall thickness measurements relative to the perfusion ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.58.4.570
更新日期:1986-04-01 00:00:00
abstract::The purpose of this study was to determine whether a quantitative relationship existed between a reduction in regional myocardial blood flow, measured by radiolabeled microspheres, and the degree and type of changes in myocardial activation recorded in bipolar left ventricular subepicardial and subendocardial electrog...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.45.6.764
更新日期:1979-12-01 00:00:00
abstract::The contractile response of the aged adult heart to beta-adrenergic stimulation is known to be reduced compared with the young adult heart. Since endogenous adenosine exerts an antiadrenergic action in the heart, this study was undertaken to determine if the basal endogenous level of myocardial adenosine increases wit...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.66.5.1381
更新日期:1990-05-01 00:00:00
abstract::The hypothesis that neurally mediated coronary vasodilation occurs as part of the carotid baroreceptor reflex was investigated. The left main coronary artery was cannulated and perfused at constant pressure (100 mm Hg) in closed-chest, chloralose-anesthetized dogs. The heart was paced at a constant rate between 60 and...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.56.4.486
更新日期:1985-04-01 00:00:00
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 co...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.117.311147
更新日期:2018-02-02 00:00:00
abstract::We studied the effects of intense sympathetic stimulation on the chronotropic responses of the heart to subsequent test stimulations of the cardiac autonomic nerves in dogs anesthetized with alpha-chloralose. Such intense sympathetic stimulations (which we refer to as "release stimulations") are known to release neuro...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.72.1.137
更新日期:1993-01-01 00:00:00
abstract:RATIONALE:Congestive heart failure (CHF) frequently results in remodeling and increased tone of pulmonary resistance vessels. This adaptive response, which aggravates pulmonary hypertension and thus, promotes right ventricular failure, has been attributed to lung endothelial dysfunction. OBJECTIVE:We applied real-time...
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pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.210542
更新日期:2010-04-02 00:00:00
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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::We have cloned from cultured vascular smooth muscle cells a protein tyrosine phosphatase, rat density-enhanced phosphatase-1 (rDEP-1), which is a probable rat homologue of DEP-1/HPTP eta. rDEP-1 is encoded by an 8.7-kb transcript and is expressed as a 180- to 220-kD protein. The rDEP-1 gene is located on human chromos...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.79.3.570
更新日期:1996-09-01 00:00:00
abstract::Blockade of angiotensin type 1 (AT1) receptors induces smooth muscle cell (SMC) death and regression of aortic hypertrophy in spontaneously hypertensive rats (SHR). We postulated that SMC death and vascular remodeling in this model may be attenuated by z-Val-Ala-Asp(OMe)-CH2F (z-VAD-fmk), a tripeptide inhibitor of cas...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000065619.36118.20
更新日期:2003-04-18 00:00:00
abstract::Pharmacological modulation of [K+]o accumulation and action potential changes during acute myocardial ischemia is under evaluation as a promising new antiarrhythmic and cardioprotective strategy during myocardial ischemia and reperfusion. We studied the effects of cromakalim, a K+ channel opener that activates ATP-sen...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.71.6.1324
更新日期:1992-12-01 00:00:00
abstract::It has been postulated that cardiopulmonary baroreceptor unloading in humans results in nonuniform activation of the sympathetic nervous system. We reasoned that simultaneous measurements of arterial and venous norepinephrine (NE) spillover and clearance (using NE kinetics), muscle sympathetic neural activity (using m...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.66.6.1720
更新日期:1990-06-01 00:00:00
abstract::The present study was undertaken to determine the mechanism of neointima formation in rabbit arteries subjected to extensive endothelial desquamation. Endothelial cells were selectively removed from the abdominal aorta by passing an inflated balloon catheter through the vessel. The healing response was then studied se...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.36.1.58
更新日期:1975-01-01 00:00:00
abstract::In nonischemic heart failure (HF), ventricular tachycardia initiates by a nonreentrant mechanism, but there is altered conduction (that could lead to re-entry) that could arise from changes in gap junctional proteins, especially connexin43 (Cx43). We studied Cx43 expression and phosphorylation state in the left ventri...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000152325.07495.5a
更新日期:2005-01-07 00:00:00
abstract::The E-cadherin/beta-catenin/T-cell factor (Tcf) signaling pathway plays a crucial role in embryogenesis and carcinogenesis and has recently emerged in atherosclerosis. The aim of this work was to investigate whether this signaling pathway is involved in smooth muscle cell proliferation induced by oxidized low-density ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.107.166405
更新日期:2008-09-26 00:00:00
abstract::To investigate the regulation of the actomyosin crossbridge cycle in cardiac muscles, the effects of ATP, ADP, Pi, and creatine phosphate (CP) on the rate of force redevelopment (ktr) were measured. We report that CP is a primary determinant in controlling the actomyosin crossbridge cycling kinetics of cardiac muscles...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000080536.06932.E3
更新日期:2003-07-11 00:00:00
abstract:RATIONALE:Activation of the mitochondrial ATP-sensitive potassium channel (mitoK(ATP)) has been implicated in the mechanism of cardiac ischemic preconditioning, yet its molecular composition is unknown. OBJECTIVE:To use an unbiased proteomic analysis of the mitochondrial inner membrane to identify the mitochondrial K(...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.112.266445
更新日期:2012-08-03 00:00:00
abstract::We determined whether cerebral arterioles in vitro adjust their diameters in response to changes in intraluminal flow rate and pressure. Intracerebral arterioles (38- to 55-microns diameter) were isolated from Sprague-Dawley rats and cannulated with a perfusion system that permitted separate control of intraluminal pr...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.77.4.832
更新日期:1995-10-01 00:00:00
abstract:RATIONALE:Thioredoxin (Trx)1 inhibits pathological cardiac hypertrophy. MicroRNAs (miRNAs) are small noncoding RNAs that downregulate posttranscriptional expression of target molecules. OBJECTIVES:We investigated the role of miRNAs in mediating the antihypertrophic effect of Trx1 on angiotensin II (Ang II)-induced car...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.110.228437
更新日期:2011-02-04 00:00:00
abstract:RATIONALE:Studies have demonstrated that exosomes can repair cardiac tissue post-myocardial infarction and recapitulate the benefits of cellular therapy. OBJECTIVE:We evaluated the role of donor age and hypoxia of human pediatric cardiac progenitor cell (CPC)-derived exosomes in a rat model of ischemia-reperfusion inj...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.309935
更新日期:2017-02-17 00:00:00
abstract::During sustained isometric exercise, central command has very little effect on muscle sympathetic nerve activity (MSNA). To determine if central command has a greater effect on MSNA during intermittent than during sustained contractions, MSNA was recorded with microelectrodes (peroneal nerve) during intermittent isome...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.76.1.127
更新日期:1995-01-01 00:00:00
abstract:RATIONALE:We studied a possibility that shRNAs can lead to transcriptional gene activation at the promoter level via epigenetic mechanism. OBJECTIVE:The purpose of this study was to test the effects on vascular endothelial growth factor (VEGF-A) expression by promoter targeted small hairpin RNAs (shRNAs) in vitro and ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.200774
更新日期:2009-09-11 00:00:00
abstract::During periodic stimulation of spontaneously beating chick heart cell aggregates, there is often an evolution of coupling patterns between the stimulator and the aggregate action potential. For example, at rapid stimulation frequencies, a rhythm that is initially 1:1 (stimulus frequency:aggregate frequency) can evolve...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.69.4.1022
更新日期:1991-10-01 00:00:00
abstract::The patch-clamp technique was used to examine the inhibition of delayed rectifier K+ channels by agents that release intracellular Ca2+. During voltage-clamp experiments on isolated myocytes with 4-aminopyridine (4-AP, 10 mmol/L) and niflumic acid (100 mumol/L) present to inhibit delayed rectifier K+ current (IK(dr)) ...
journal_title:Circulation research
pub_type: 杂志文章,收录出版
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更新日期:1995-07-01 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
abstract::Cultured quail myocytes were much more resistant to H2O2 toxicity than cultured mouse myocytes. The intracellular concentration of glutathione ([GSH]i) and the activity of gamma-glutamylcysteine synthetase (gamma-GCS) in quail heart cells were about five and three times higher, respectively, than in mouse heart cells,...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.74.5.806
更新日期:1994-05-01 00:00:00
abstract:RATIONALE:Angiotensin-converting enzyme (ACE)2 opposes the actions of angiotensin (Ang) II by degrading it to Ang 1-7. OBJECTIVE:Given the important role of Ang II/Ang 1-7 in atherogenesis, we investigated the impact of ACE2 deficiency on the development of atherosclerosis. METHODS AND RESULTS:C57Bl6, Ace2 knockout (...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.110.219279
更新日期:2010-10-01 00:00:00
abstract::In isolated right atria of the rabbit heart, we studied the activation pattern within the sinus node, using the microelectrode technique. After the electrophysiological experiments, the preparations were subjected to a correlative morphological investigation, using light or electron microscopy. Different criteria for ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.46.1.11
更新日期:1980-01-01 00:00:00
abstract:RATIONALE:One goal of cardiac tissue engineering is the generation of a living, human pump in vitro that could replace animal models and eventually serve as an in vivo therapeutic. Models that replicate the geometrically complex structure of the heart, harboring chambers and large vessels with soft biomaterials, can be...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.119.316155
更新日期:2020-07-03 00:00:00
abstract:RATIONALE:Voltage-gated sodium channels initiate action potentials in excitable tissues. Mice in which Scn5A (the predominant sodium channel gene in heart) has been knocked out die early in development with cardiac malformations by mechanisms which have yet to be determined. OBJECTIVE:Here we addressed this question b...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.213132
更新日期:2010-04-30 00:00:00