Role of histamine H1 and H2 receptor antagonists in the prevention of intimal thickening

Miyazawa, Norio; Watanabe, Shinji; Matsuda, Akihisa; Kondo, Kazunao; Hashimoto, Hisakuni; Umemura, Kazuo; Nakashima, Mitsuyoshi

doi:10.1016/s0014-2999(98)00716-x

Cited by 52 publications

(39 citation statements)

References 27 publications

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“…Thus, the action of histamine on TNF-a and thrombin-induced TF expression is mediated via the H 1 -receptor. Activation of this receptor plays an important role in the pathogenesis of vasospasm, vascular inflammation, and intimal thickening after vascular injury [21][22][23]. Thus, our data add to the growing evidence that histamine-induced vascular dysfunction is mediated through activation of the H 1 -receptor.…”

Section: Discussionsupporting

confidence: 66%

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: Discussionsupporting

confidence: 66%

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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“…One of these studies showed that the histamine H1 receptor antagonist reduced intimal hyperplasia (13); the other study reported that histamine synthesis enzyme knock-out mice (HDC Ϫ/Ϫ mice) showed reduced neointimal thickening and a decreased intima-to-media thickness ratio (14). In regard to how histamine influences inflammation and atherosclerosis in endothelial cells, evidence has shown that histamine induces expression of genes such as p-selectin (9), ICAM1, VCAM1 (10), IL6, IL8 (8), cyclooxygenase-2 (27), and tissue factor (11).…”

Section: Discussionmentioning

confidence: 99%

“…Histamine also induces tissue factor expression in smooth muscle cells (11), and smooth muscle cell proliferation (12,13). Most importantly, the antagonists of histamine receptor 1 (H1) reduce thickened intimas in mice (13), and recently, HDC knock-out mice showed reduced neointimal thickening (14). All of this accumulating evidence supports the notion that histamine promotes the development and progression of atherosclerosis.…”

mentioning

confidence: 82%

“…Histamine induces endothelial cells to produce proinflammatory cytokines such as interleukin 6 (IL6) and interleukin 8 (IL8) (6 -8); adherent molecules such as p-selectin (9), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) (10), and tissue factor (11), a prominent initiator of blood coagulation. Histamine also induces tissue factor expression in smooth muscle cells (11), and smooth muscle cell proliferation (12,13). Most importantly, the antagonists of histamine receptor 1 (H1) reduce thickened intimas in mice (13), and recently, HDC knock-out mice showed reduced neointimal thickening (14).…”

mentioning

confidence: 99%

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Histamine Induces Egr-1 Expression in Human Aortic Endothelial Cells via the H1 Receptor-mediated Protein Kinase Cδ-dependent ERK Activation Pathway

Feng

Tan

et al. 2008

Journal of Biological Chemistry

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Histamine, a potent inflammatory mediator, has multiple effects on the pathogenesis of atherosclerosis. This study investigates the effect of histamine on the expression of early growth response factor 1 (Egr-1), a master transcription factor that regulates the expression of an array of atherogenic genes in atherosclerotic lesions. Histamine markedly and rapidly induces Egr-1 mRNA and protein expression in primary human aortic endothelial cells (HAECs). Histamine-induced Egr-1 expression is dependent on the activation of the H1 receptor. Histamine also rapidly and transiently activates protein kinase C-␦ (PKC␦), extracellular signal-regulated kinase (ERK)1/2, p38 kinase, and c-Jun N-terminal kinase (JNK) prior to Egr-1 induction. Using specific pharmacological inhibitors and small interfering RNA technology, we determined that PKC␦ and ERK, but not p38 and JNK, mediate histamine-induced Egr-1 expression. Our data provide the first evidence that histamine regulates expression of Egr-1 in mammalian cells and demonstrate a novel role of PKC␦ in up-regulation of Egr-1 expression. The present study reveals the following regulatory mechanism: histamine up-regulates Egr-1 expression in primary HAECs via the H1 receptor and the PKC␦-dependent ERK activation pathway. Our data also imply that CREB, a downstream component of the ERK pathway, regulates Egr-1 expression in HAECs. Importantly, these results suggest a central role of Egr-1 in histamine-induced gene expression and in histamine-induced vascular disease.

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“…Histamine has also been shown to increase smooth muscle cell proliferation and migration, 6 and it has been implicated in intimal thickening and atherogenesis. 14,15 In animal models, antihistamines provided protection against intimal thickening and the development of atherosclerosis. 14 In conditions of oxidative stress and atherosclerosis, eNOS can "uncouple" and become dysfunctional.…”

mentioning

confidence: 99%

Histamine Upregulates Gene Expression of Endothelial Nitric Oxide Synthase in Human Vascular Endothelial Cells

Burkhardt

Heinrich

et al. 2003

Circulation

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Background-Histamine has a short-term, transient, stimulating effect on endothelial nitric oxide synthase (eNOS) activity; however, long-term effects on eNOS have not been described yet. In addition, the vascular effect of histamine seems to depend critically on eNOS functionality. Therefore, we studied the effects of histamine on eNOS gene expression and function. Methods and Results-In human umbilical vein endothelial cells (HUVECs) and HUVEC-derived EA.hy 926 cells, histamine upregulated eNOS mRNA (RNase protection assay) and protein (electron microscopic immunocytochemistry) expression. The upregulation of eNOS could be prevented by mepyramine, a selective antagonist at the H 1 receptor, but not by H 2 and H 3 receptor antagonists. Incubation of EA.hy 926 cells with histamine led to the activation of calcium/calmodulin-dependent protein kinase II (CaMK II; in vitro phosphorylation assay). The histamine-induced eNOS expression was completely prevented by KN-93, an inhibitor of CaMK II. Histamine increased the activity of a 1.6-kb human eNOS promoter fragment (luciferase reporter gene assay), an effect that was also blocked by mepyramine. Under normal conditions, eNOS upregulation by histamine resulted in increased nitric oxide production (measured by nitric oxide chemiluminescence and RFL-6 reporter cell assay). Under conditions of oxidative stress, however, the eNOS upregulated by histamine produced reactive oxygen species (CM-H 2 DCFDA oxidation-based fluorescence assay). Conclusions-Stimulation of the H 1 receptor increases eNOS transcription in endothelial cells by a signaling pathway involving CaMK II. This eNOS upregulation may be protective under normal conditions, but it may become harmful under conditions of oxidative stress when eNOS produces reactive oxygen species at the expense of nitric oxide.

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Role of histamine H1 and H2 receptor antagonists in the prevention of intimal thickening

Cited by 52 publications

References 27 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

Histamine Induces Egr-1 Expression in Human Aortic Endothelial Cells via the H1 Receptor-mediated Protein Kinase Cδ-dependent ERK Activation Pathway

Histamine Upregulates Gene Expression of Endothelial Nitric Oxide Synthase in Human Vascular Endothelial Cells

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