Statin Prevents Tissue Factor Expression in Human Endothelial Cells

Eto, Masato; Kozai, Toshiyuki; Cosentino, Francesco; Joch, Hana; Lüscher, Thomas F.

doi:10.1161/01.cir.0000015465.73933.3b

Cited by 317 publications

(256 citation statements)

References 19 publications

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“…Both p38 and JNK are involved in TF induction by histamine [13], TNF-a [14,18], and thrombin [18,26]. As the two MAPKs mediated TF induction by TNF-a and thrombin in both the presence and the absence of histamine, we sought to determine whether p38 or JNK could be involved in the differential augmenting effect of histamine on TNF-a-vs. thrombin-induced TF expression.…”

Section: Discussionmentioning

confidence: 99%

Histamine differentially interacts with tumor necrosis factor‐α and thrombin in endothelial tissue factor induction: the role of c‐Jun NH2‐terminal kinase

Steffel

Arnet

Akhmedov

et al. 2006

Journal of Thrombosis and Haemostasis

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Summary. Background: Histamine plays an important role in vascular disease. Tissue factor (TF) expression is induced in vascular inflammation and acute coronary syndromes. Objectives: This study examined the effect of histamine on tumor necrosis factor‐α‐ (TNF‐α‐) vs. thrombin‐induced endothelial TF expression. Methods and results: Histamine (10−8–10−5 mol L−1), TNF‐α (5 ng mL−1), and thrombin (1 U mL−1) induced TF expression in human endothelial cells. Although TF expression by TNF‐α and thrombin was identical, histamine augmented TNF‐α‐induced expression 7.0‐fold, but thrombin‐induced expression only 2.6‐fold. Similar responses occurred with TF activity. The H1‐receptor antagonist mepyramine abrogated these effects. Differential augmentation by histamine was also observed at the mRNA level. Histamine‐induced p38 activation preceded a weak second activation to both TNF‐α and thrombin. Histamine‐induced c‐Jun NH2‐terminal kinase (JNK) activation was followed by a strong second activation to TNF‐α, and less to thrombin. Selective inhibition of this second JNK activation by SP600125 reduced TF induction to histamine plus TNF‐α by 67%, but to histamine plus thrombin by only 32%. Histamine augmented TNF‐α‐ and thrombin‐induced vascular cell adhesion molecule 1 (VCAM‐1) expression to a similar extent. Consistent with this observation, VCAM‐1 induction to TNF‐α and thrombin was mediated by p38, but not by JNK. Conclusions: Histamine differentially augments TNF‐α‐ vs. thrombin‐induced TF expression and activity, which is mediated by the H1‐receptor, occurs at the mRNA level, and is related to differential JNK activation.

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Section: Discussionmentioning

confidence: 99%

Histamine differentially interacts with tumor necrosis factor‐α and thrombin in endothelial tissue factor induction: the role of c‐Jun NH2‐terminal kinase

Steffel

Arnet

Akhmedov

et al. 2006

Journal of Thrombosis and Haemostasis

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“…At the level of the vasculature, statins have been shown to increase endothelium-derived nitric oxide production, 51 reduce vascular inflammation, 52 and reduce the volume of hematoma in hemorrhagic stroke. 53 There are also reports that statins decrease platelet aggregation and thrombosis.…”

Section: Statinsmentioning

confidence: 99%

Multifunctional Drugs for Head Injury

2009

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Summary: Traumatic brain injury (TBI) remains one of the leading causes of mortality and morbidity worldwide in individuals under the age of 45 years, and, despite extensive efforts to develop neuroprotective therapies, there has been no successful outcome in any trial of neuroprotection to date. In addition to recognizing that many TBI clinical trials have not been optimally designed to detect potential efficacy, the failures can be attributed largely to the fact that most of the therapies investigated have been targeted toward an individual injury factor. The contemporary view of TBI is that of a very heterogenous type of injury, one that varies widely in etiology, clinical presentation, severity, and pathophysiology. The mechanisms involved in neuronal cell death after TBI involve an interaction of acute and delayed anatomic, molecular, biochemical, and physiological events that are both complex and multifaceted. Accordingly, neuropharmacotherapies need to be targeted at the multiple injury factors that contribute to the secondary injury cascade, and, in so doing, maximize the likelihood of a successful outcome. This review focuses on a number of such multifunctional compounds that have shown considerable success in experimental studies and that show maximum promise for success in clinical trials.

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“…ROCK regulates endothelial tissue factor expression, which is critical for atherothrombosis [79,80]. Indeed, treatment with Y-27632 decreased atherosclerotic lesion size by approximately 30% in LDLreceptor knockout mice [81].…”

Section: Rock In Vascular Remodeling and Atherosclerosismentioning

confidence: 99%

ROCKs as therapeutic targets in cardiovascular diseases

Rikitake

Liao

2005

Expert Review of Cardiovascular Therapy

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There is growing evidence that Rho-kinases (ROCKs), the immediate downstream targets of the small guanosine triphosphate-binding protein Rho, may contribute to cardiovascular disease. ROCKs play a central role in diverse cellular functions such as smooth muscle contraction, stress fiber formation and cell migration and proliferation. Overactivity of ROCKs is observed in cerebral ischemia, coronary vasospasm, hypertension, vascular inflammation, arteriosclerosis and atherosclerosis. ROCKs, therefore, may be an important and still relatively unexplored therapeutic target in cardiovascular disease. Recent experimental and clinical studies using ROCK inhibitors such as Y-27632 and fasudil have revealed a critical role of ROCKs in embryonic development, inflammation and oncogenesis. This review will focus on the potential role of ROCKs in cellular functions and discuss the prospects of ROCK inhibitors as emerging therapy for cardiovascular diseases. Keywords contraction; endothelium; hypertension; inflammation; leukocyte; remodeling; Rho-kinase; smooth muscleThe small guanosine triphosphate (GTP)-binding proteins belonging to the Rho family regulate various aspects of cell shape, motility, proliferation and apoptosis [1]. Rho-kinases (ROCKs), which were one of the first downstream effectors of Rho to be discovered [2-4], were found to mediate RhoA-induced actin cytoskeletal changes through effects on myosin light-chain (MLC) phosphorylation [5,6]. ROCKs are protein serine/threonine kinases that share 45-50% homology with other actin cytoskeletal kinases such as myotonic dystrophy kinase (DMPK), myotonic dystrophy-related cdc42-binding kinase (MRCK) and citron kinase [1]. ROCKs consist of an amino-terminal kinase domain, followed by a mid-coiled-coil-forming region containing a Rho-binding domain (RBD) and a carboxy-terminal cysteine-rich domain (CRD) located within the pleckstrin homology (PH) motif (FIGURE 1). In mammalian systems, two ROCK isoforms have been identified. ROCK1, which is also known as ROKβ, and p160ROCK, which is located on chromosome 18 and encodes a 1354 amino acid protein [4,5]. ROCK2, which is also known as ROKα and sometimes confusingly called Rho-kinase, is located on chromosome 12 and contains 1388 amino acids [2,7,8]. ROCK1 and 2 share an overall 65% homology in amino acid sequence and 92% homology in their kinase domains

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Statin Prevents Tissue Factor Expression in Human Endothelial Cells

Cited by 317 publications

References 19 publications

Histamine differentially interacts with tumor necrosis factor‐α and thrombin in endothelial tissue factor induction: the role of c‐Jun NH2‐terminal kinase

Histamine differentially interacts with tumor necrosis factor‐α and thrombin in endothelial tissue factor induction: the role of c‐Jun NH2‐terminal kinase

Multifunctional Drugs for Head Injury

ROCKs as therapeutic targets in cardiovascular diseases

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