Abstract:
:Platelet hyperactivity associated with hyperlipidemia may contribute to development of a prothrombotic state. We previously showed that oxidized low-density lipoprotein (oxLDL) formed in the setting of hyperlipidemia and atherosclerosis activated platelets in a CD36-dependent manner. We now show that mitogen-activated protein kinase c-Jun N-terminal kinase (JNK)2 and its upstream activator MKK4 were phosphorylated in platelets exposed to oxLDL. Using apoE(-/-) mice as a model of hyperlipidemia, we showed that JNK was constitutively phosphorylated in platelets in a CD36-dependent manner. Inhibition of src kinase activity reduced JNK phosphorylation by oxLDL. Immunoprecipitations revealed that active phosphorylated forms of src kinases Fyn and Lyn were recruited to CD36 in platelets exposed to oxLDL. Pharmacological inhibition of the mitogen-activated protein kinase JNK or src family kinases abolished platelet activation by oxLDL in vitro. Using a murine carotid artery thrombosis model we demonstrated CD36-dependent phosphorylation of platelet JNK within thrombi. Furthermore, pharmacological inhibition of JNK prolonged thrombosis times in wild-type but not cd36-null mice in vivo. These findings suggest that a specific CD36-dependent signaling pathway is required for platelet activation by oxLDL and may provide insights related to development of novel antiplatelet therapies more relevant to atherothrombosis than to normal hemostasis.
journal_name
Circ Resjournal_title
Circulation researchauthors
Chen K,Febbraio M,Li W,Silverstein RLdoi
10.1161/CIRCRESAHA.108.172064subject
Has Abstractpub_date
2008-06-20 00:00:00pages
1512-9issue
12eissn
0009-7330issn
1524-4571pii
CIRCRESAHA.108.172064journal_volume
102pub_type
杂志文章abstract::Activation of protein kinase C has been implicated in the regulation of a variety of cellular reactions. Although we, and others, have found protein kinase C and its substrate proteins to be present in both membrane and cytosolic fractions in the heart, the physiologic role of this kinase in the regulation of cardiac ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.61.3.372
更新日期:1987-09-01 00:00:00
abstract::Three different isoforms of the inhibitory guanine nucleotide-binding protein alpha-subunit (Gi alpha) have been cloned. However, little information on the cardiac-specific expression of these isoforms is available. The deduced amino acid sequence of a full-length Gi alpha 2 complementary DNA from a canine ventricular...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.65.4.1136
更新日期:1989-10-01 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:RATIONALE:Obesity leads to increased ischemic heart disease (IHD) risk, but the risk is thought to be mediated through intermediate variables and may not be caused by increased weight per se. OBJECTIVE:To test the hypothesis that the increased IHD risk because of obesity is mediated through lipoproteins, blood pressur...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.304846
更新日期:2015-02-13 00:00:00
abstract::Tissue factor (TF) is a low-molecular-weight glycoprotein that initiates the extrinsic clotting cascade and is considered a major regulator of arterial thrombogenicity. TF pathway inhibitor (TFPI) is a major physiological inhibitor of TF-initiated coagulation. The aim of this study was to define the complex interplay ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh1301.092508
更新日期:2001-07-06 00:00:00
abstract::We measured pressure-volume curves in nine excised dog ventricles and stress-strain curves in two to five muscle specimens from each ventricle to verify a derived formula that relates muscle stiffness to the ventricular pressure-volume curve. The assumptions underlying this formula are: (1) the ventricle is a uniform ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.37.6.787
更新日期:1975-12-01 00:00:00
abstract::Endothelium-dependent hyperpolarization and relaxation of vascular smooth muscle are mediated by endothelium-derived hyperpolarizing factors (EDHFs). EDHF candidates include cytochrome P-450 metabolites of arachidonic acid, K(+), hydrogen peroxide, or electrical coupling through gap junctions. In bovine coronary arter...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000018162.87285.f8
更新日期:2002-05-17 00:00:00
abstract::Recent advances in cardiac physiology identify the integrin-linked kinase (ILK) as an essential molecule regulating cardiac growth, contractility, and repair. A key transducer of biochemical signals initiated at the plasma membrane by cell-matrix interactions, ILK now emerges as a crucial player in mechanotransduction...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.RES.0000265233.40455.62
更新日期:2007-05-25 00:00:00
abstract::Recent studies have shown that the primary heart tube continues to grow by addition of cells from the coelomic wall. This growth occurs concomitantly with embryonic folding and formation of the coelomic cavity, making early heart formation morphologically complex. A scarcity of data on localized growth parameters furt...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.108.185843
更新日期:2009-01-30 00:00:00
abstract::In urethane-anesthetized rats, electrophysiological recordings of spontaneously active neurons in the vasopressor area of the rostral ventrolateral medulla were analyzed for participation in cardiovascular regulation. A total of 138 units were found which were inhibited by transient increases in mean arterial pressure...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.56.3.359
更新日期:1985-03-01 00:00:00
abstract::Transient coronary occlusion (15 minutes) does not result in irreversible myocardial injury but is associated with a depression of contractile function sustained for several hours to days ("stunned myocardium"). The defect in the contractile process responsible for this phenomenon has been suggested to be causally rel...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.61.6.834
更新日期:1987-12-01 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::Vascular remodeling, rather than vasoconstriction, is believed to account for high vascular resistance in severe pulmonary arterial hypertension (PAH). We have found previously that acute Rho kinase inhibition nearly normalizes PAH in chronically hypoxic rats that have no occlusive neointimal lesions. Here we examined...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000261658.12024.18
更新日期:2007-03-30 00:00:00
abstract::Myocardial responses to acute ischemia/reperfusion and to chronic ischemic conditions have been studied extensively at all levels of organization. These include subcellular (eg, mitochondria in vitro); intact, large animal models (eg, swine with chronic coronary stenosis); as well as human subjects. Investigations in ...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.116.307898
更新日期:2017-03-31 00:00:00
abstract::We studied the effects of rapid atrial pacing during the final 10 minutes of a 70-minute, 31% reduction in coronary blood flow in anesthetized swine to understand the significance of apparent metabolic improvements during the initial 60 minutes of segmental ischemia. Within 5-10 minutes of ischemia, subendocardial pho...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.69.6.1458
更新日期:1991-12-01 00:00:00
abstract::The hallmark of most cardiac diseases is the progressive loss of cardiomyocytes. In the perinatal period, cardiomyocytes still proliferate, and the heart shows the capacity to regenerate upon injury. In the adult heart, however, the actual rate of cardiomyocyte renewal is too low to efficiently counteract substantial ...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.119.315408
更新日期:2020-02-14 00:00:00
abstract:RATIONALE:Sarcoplasmic reticulum (SR) Ca(2+) cycling is key to normal excitation-contraction coupling but may also contribute to pathological cardiac alternans and arrhythmia. OBJECTIVE:To measure intra-SR free [Ca(2+)] ([Ca(2+)]SR) changes in intact hearts during alternans and ventricular fibrillation (VF). METHODS ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.114.302505
更新日期:2014-04-25 00:00:00
abstract::We carried out a systematic study on the effects of elevating [K]o on the properties of a transient outward potassium channel encoded by a cardiac cDNA (RHK1) and compared them with those on two Shaker potassium channels (H-4 and H-37). The amino acid sequences of all three channels are known, and their structure-func...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.71.3.657
更新日期:1992-09-01 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 potential for heparin to enhance the training-induced increase in collateral-dependent blood flow to the distal hind-limb muscles was evaluated after bilateral femoral artery ligation in adult male rats (approximately 350 g). Rats received either saline (n = 34) or heparin (n = 36) injections and were kept sedenta...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.76.3.448
更新日期:1995-03-01 00:00:00
abstract::The present study was performed to examine the mechanism by which cyclooxygenase blockade produces vasoconstriction in well-developed coronary collateral vessels. Eight dogs were studied 4 to 6 months after occlusion of the left anterior descending coronary artery (LAD) had been performed to stimulate collateral vesse...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.74.2.310
更新日期:1994-02-01 00:00:00
abstract::Fractalkine, a chemokine expressed by inflamed endothelium, induces leukocyte adhesion and migration via the receptor CX3CR1, and the CX3CR1 polymorphism V249I affects receptor expression and function. Here we show that this polymorphism is an independent risk factor for atherosclerotic coronary artery disease (CAD). ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh1701.095642
更新日期:2001-08-31 00:00:00
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 hypert...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.116.307474
更新日期:2016-05-13 00:00:00
abstract::Oxygen free radicals have the ability to oxidize cholesterol. However, nothing is known about the effects of cholesterol oxidation on ion transport in isolated myocardial membranes. The purpose of the present study was to investigate the effects of in situ oxidative modification of sarcolemmal cholesterol on Ca2+ flux...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.68.1.18
更新日期:1991-01-01 00:00:00
abstract::Net cellular L-lactate efflux associated with accelerated anaerobic glycolysis has been implicated as a potential cause of the marked cellular K+ loss contributing to lethal cardiac arrhythmias in ischemic heart and to impaired function of fatigued skeletal muscle. To examine the mechanisms of transsarcolemmal L-lacta...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.74.5.829
更新日期:1994-05-01 00:00:00
abstract::The synthesis of an angiotensin II (A II) antagonist, sarcosyl1-cysteinyl(S-methyl)8-angiotensin II [Sar1-Cys(Me)8-A II], showing partial organ selectivity and properties of a noncompetitive antagonist, is described. The compound was found to be an extremely potent antagonist on vascular smooth muscle both in vitro (p...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.46.5.720
更新日期:1980-05-01 00:00:00
abstract::Inflammatory processes underlie a broad spectrum of conditions that injure the heart muscle and cause both structural and functional deficits. In this article, we address current knowledge regarding 4 common forms of myocardial inflammation: myocardial ischemia and reperfusion, sepsis, viral myocarditis, and immune re...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.111.243170
更新日期:2012-01-06 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: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-interacti...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.304899
更新日期:2015-02-13 00:00:00
abstract::The responses of cardiac mitochondria to anoxia may be evaluated in terms of the oxidation-reduction state of the electron carriers and the ability of the mitochondria to function in energy-linked reactions. The previous detailed evaluation of the oxygen requirements for electron transfer in mitochondria is here exten...
journal_title:Circulation research
pub_type: 杂志文章
doi:
更新日期:1976-05-01 00:00:00