Abstract:
RATIONALE:Cryptogenic strokes, those of unknown cause, have been estimated as high as 30% to 40% of strokes. Inflammation has been suggested as a critical etiologic factor. However, there is lack of experimental evidence. OBJECTIVE:In this study, we investigated inflammation-associated stroke using a mouse model that developed spontaneous stroke because of myeloid deficiency of TGF-β (transforming growth factor-β) signaling. METHODS AND RESULTS:We report that mice with deletion of Tgfbr2 in myeloid cells (Tgfbr2Myeko) developed cerebrovascular inflammation in the absence of significant pathology in other tissues, culminating in stroke and severe neurological deficits with 100% penetrance. The stroke phenotype can be transferred to syngeneic wild-type mice via Tgfbr2Myeko bone marrow transplant and can be rescued in Tgfbr2Myeko mice with wild-type bone marrow. The underlying mechanisms involved an increased type 1 inflammation and cerebral endotheliopathy, characterized by elevated NF-κB (nuclear factor-κB) activation and TNF (tumor necrosis factor) production by myeloid cells. A high-fat diet accelerated stroke incidence. Anti-TNF treatment, as well as metformin and methotrexate, which are associated with decreased stroke risk in population studies, delayed stroke occurrence. CONCLUSIONS:Our studies show that TGF-β signaling in myeloid cells is required for maintenance of vascular health and provide insight into inflammation-mediated cerebrovascular disease and stroke.
journal_name
Circ Resjournal_title
Circulation researchauthors
Hollander MC,Latour LL,Yang D,Ishii H,Xiao Z,Min Y,Ray-Choudhury A,Munasinghe J,Merchant AS,Lin PC,Hallenbeck J,Boehm M,Yang Ldoi
10.1161/CIRCRESAHA.116.310349subject
Has Abstractpub_date
2017-12-08 00:00:00pages
1360-1369issue
12eissn
0009-7330issn
1524-4571pii
CIRCRESAHA.116.310349journal_volume
121pub_type
杂志文章abstract::Glibenclamide, one of the antidiabetic sulfonylureas, is known to block ATP-dependent K+ channels. We used this drug to determine to what extent K+ loss from acutely ischemic myocardium is mediated via these channels. We also investigated whether glibenclamide would influence ischemic arrhythmias. Isolated rat hearts ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.66.2.478
更新日期:1990-02-01 00:00:00
abstract::This article examines the role of innervation in regulating expression of acetylcholinesterase (AchE), butyrylcholinesterase (BuchE), and the muscarinic acetylcholine receptor (mAchR) in avian heart. Two distinct approaches are taken. The first approach examines the relation between the onsets of parasympathetic and s...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.70.4.633
更新日期:1992-04-01 00:00:00
abstract::In addition to its role in reverse cholesterol transport, high-density lipoprotein (HDL) cholesterol has direct action on numerous cell types that influence cardiovascular and metabolic health. Cellular responses to HDL entail its capacity to invoke cholesterol efflux that causes signal initiation via scavenger recept...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.111.258673
更新日期:2012-09-28 00:00:00
abstract::The mechanism of propranolol-inhibited sarcolemmal membrane lipid peroxidation was investigated by electron spin resonance spin-trapping technique using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and 2-methyl-2-nitrosopropane (MNP). Highly purified canine myocytic sarcolemma were peroxidized by a superoxide-driven (from ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.65.4.1151
更新日期:1989-10-01 00:00:00
abstract::Vascular endothelial cells respond to laminar shear stress by aligning in the direction of flow, a process which may contribute to atheroprotection. Here we report that localized alpha4 integrin phosphorylation is a mechanism for establishing the directionality of shear stress-induced alignment in microvascular endoth...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.108.176354
更新日期:2008-07-18 00:00:00
abstract:RATIONALE:Remote ischemic conditioning (RIC) or ischemic postconditioning (PostC) may protect the myocardium from ischemia-reperfusion injury in patients with ST-segment-elevation myocardial infarction. OBJECTIVE:To determine whether combined intrahospital RIC and PostC or PostC alone in addition to primary percutaneo...
journal_title:Circulation research
pub_type: 杂志文章,随机对照试验
doi:10.1161/CIRCRESAHA.118.314500
更新日期:2019-05-10 00:00:00
abstract::Studies were performed to determine whether an alteration in coronary vascular resistance and a reduction in the reflow phenomenon occurred in the blood-perfused, heparinized canine heart after various periods of myocaridal ischemia. Regional myocardial blood flow was measured with radioactive microspheres. Proximal l...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.36.6.771
更新日期:1975-06-01 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::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::An affinity gel for the purification of renin was prepared by coupling pepstatin to aminohexylagarose gel. Partially purified human renin (Haas et al., Arch. Biochem. Biophys., 110, 534-543, 1965) was purified further by affinity chromatography on the pepstatin-aminohexyl-agarose gel, gel filtration on a Sephadex G-75...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.41.4.4
更新日期:1977-10-01 00:00:00
abstract::The accumulation of inositol 1,4,5-trisphosphate (IP3) after hormonal stimulation has a physiological role, possibly by alteration of Ca2+ levels in cardiac myocyte. However, this accumulation has not been studied under pathophysiological conditions. In this report, we examine phosphatidylinositol metabolism during ce...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.72.5.966
更新日期:1993-05-01 00:00:00
abstract::Platelet activation is markedly increased during coronary thrombolysis and limits the response to thrombolytic therapy. A possible mediator of platelet activation in this setting is thromboxane (TX) A2, a potent platelet agonist formed in greatly increased amounts during coronary thrombolysis in man. To address this h...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.65.1.83
更新日期:1989-07-01 00:00:00
abstract:RATIONALE:Mechanisms of angiogenesis in skeletal muscle remain poorly understood. Efforts to induce physiological angiogenesis hold promise for the treatment of diabetic microvascular disease and peripheral artery disease but are hindered by the complexity of physiological angiogenesis and by the poor angiogenic respon...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.115.303829
更新日期:2014-08-15 00:00:00
abstract:RATIONALE:Mitochondria are key integrators of convergent intracellular signaling pathways. Two important second messengers modulated by mitochondria are calcium and reactive oxygen species. To date, coherent mechanisms describing mitochondrial integration of calcium and oxidative signaling in arterial smooth muscle are...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.115.306996
更新日期:2015-12-04 00:00:00
abstract::The phorbol ester 12-O-tetradecanoyl phorbol-13-acetate was used to probe the role of protein kinase-C in the modulation of alpha-adrenergic receptor-coupled calcium efflux in cultured vascular smooth muscle cells derived from rabbit aorta. Exposure of cells to 12-O-tetradecanoyl phorbol-13-acetate for 6 minutes cause...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.58.3.393
更新日期:1986-03-01 00:00:00
abstract::Lipid rafts are discrete membrane subdomains rich in sphingolipids and cholesterol. In ventricular myocytes a function of caveolae, a type of lipid rafts, is to concentrate in close proximity several proteins of the beta-adrenergic transduction pathway. We have investigated the subcellular localization of HCN4 channel...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000127621.54132.AE
更新日期:2004-05-28 00:00:00
abstract:RATIONALE:Hypoxia followed by reoxygenation promotes inflammation by activating nuclear factor κB transcription factors in endothelial cells (ECs). This process involves modification of the signaling intermediary tumor necrosis factor receptor-associated factor 6 with polyubiquitin chains. Thus, cellular mechanisms tha...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.111.300119
更新日期:2013-06-07 00:00:00
abstract:RATIONALE:The mammalian diaphanous-related formin (mDia1), governs microtubule and microfilament dynamics while functioning as an effector for Rho small GTP-binding proteins during key cellular processes such as adhesion, cytokinesis, cell polarity, and morphogenesis. The cytoplasmic domain of the receptor for advanced...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.111.262519
更新日期:2012-05-11 00:00:00
abstract::We studied the effect of histamine and H1 or H2 blockers on the diameter of pial arteries (39-227 micron) using microapplication into the perivascular space. Concentration-response curves for histamine showed dilations which started at 10(-7) M and were maximal at 10(-5) and 10(-4) M. The H2 blocker, cimetidine, induc...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.44.2.161
更新日期:1979-02-01 00:00:00
abstract::Peripheral blood (PB)-derived CD14+ monocytes were shown to transdifferentiate into endothelial cell (EC) lineage cells and contribute to neovascularization. We investigated whether bone marrow (BM)- or PB-derived CD34-/CD14+ cells are involved in reendothelialization after carotid balloon injury. Although neither hem...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000099245.08637.CE
更新日期:2003-11-14 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: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::Adenosine modulates a variety of cellular functions by interacting with specific cell surface G protein-coupled receptors (A1, A2A, A2B, and A3) and is a potential mediator of angiogenesis through the A2B receptor. The lack of a potent, selective A2B receptor inhibitor has hampered its characterization. Our goal was t...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000091260.78959.BC
更新日期:2003-09-19 00:00:00
abstract::Apoptosis of smooth muscle cells (SMC) and degradation of the extracellular matrix (ECM) have both been implicated in atherosclerotic plaque rupture. We have previously reported that degraded type I collagen fragments induce a rapid but transient apoptotic burst initiated by calpains in SMC. The aim of the current stu...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000229267.77982.0d
更新日期:2006-06-23 00:00:00
abstract::The major goal of this study was to determine the interactions of VLDL surface and core lipids with the artery wall. We first demonstrated in vitro that surface lipid in VLDL could be traced using the phospholipid-like fluorescent probe 1,1'-dioctadecyl-3,3, 3',3'-tetramethyl-indocarbocyanine (DiI). The core of VLDL p...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.86.7.768
更新日期:2000-04-14 00:00:00
abstract::Alveolar epithelial beta-adrenergic receptor (betaAR) activation accelerates active Na+ transport in lung epithelial cells in vitro and speeds alveolar edema resolution in human lung tissue and normal and injured animal lungs. Whether these receptors are essential for alveolar fluid clearance (AFC) or if other mechani...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000125623.56442.20
更新日期:2004-04-30 00:00:00
abstract::The blood pressure of rabbits with chronic one-kidney hypertension can be lowered to normal by immunization with hog kidney cortex preparations that do not contain renin, thus providing evidence for a new factor essential for the maintenance of an elevated blood pressure. A search for the new factor has led to the dis...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.40.2.143
更新日期:1977-02-01 00:00:00
abstract:RATIONALE:Long noncoding RNAs (lncRNAs) constitute a novel class of noncoding RNAs that regulate gene expression. Although recent data suggest that lncRNAs may be associated with cardiac disease, little is known about lncRNAs in the setting of myocardial ischemia. OBJECTIVE:To measure lncRNAs in patients with myocardi...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.115.303836
更新日期:2014-09-12 00:00:00
abstract::Sinus node recovery time was compared to the recovery time of a slow atrioventricular junctional rhythm in each of the same seven pentobarbital anesthetized dogs. Recovery time and the first five cardiac cycles were examined after pacing atria and ventricles for 20, 40, and 60 seconds at four or more pacing cycle leng...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.57.1.182
更新日期:1985-07-01 00:00:00
abstract::Our previous studies suggested that enhanced fibronectin mRNA translation in ductus arteriosus compared with aortic smooth muscle cells is related to increased expression of light chain 3 (LC3) of microtubule-associated protein 1, which binds an AU-rich element in the 3' untranslated region of fibronectin mRNA. We the...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.83.5.481
更新日期:1998-09-07 00:00:00