Activation of heat shock protein (hsp)70 and proto-oncogene expression by alpha1 adrenergic agonist in rat aorta with age.

Chin, Jane H.; Okazaki, Masahiro; Hu, Zhiwei; Miller, Jeffrey W.; Hoffman, Brian B.

doi:10.1172/jci118674

Cited by 46 publications

(42 citation statements)

References 42 publications

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“…To provide a better link to in vivo processes, we sought confirmation in a rat aortic ring model commonly used to examine vascular responses to injurious stimuli ex vivo (20) and a mouse model of vascular chlamydial infection (14). The advantage of the aortic ring is the good control of the infection initiated.…”

Section: Discussionmentioning

confidence: 99%

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Chlamydia pneumoniae infection promotes a proliferative phenotype in the vasculature through Egr-1 activation in vitro and in vivo

Rupp¹,

Hellwig-Bürgel²,

Wobbe³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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Atherosclerosis is characterized by inflammation and proliferation of vascular cells. The intracellular bacterium Chlamydia (Chlamydophila) pneumoniae uses blood monocytes [peripheral blood mononuclear cells (PBMCs)] for dissemination, has been found to persist in atherosclerotic lesions, and has been implicated in atherogenesis by small GTPase activation and T lymphocyte recruitment. Infection of human coronary artery smooth muscle cells with C. pneumoniae significantly induced mRNA and protein for the angiogenic transcription factor Egr-1, resulting in enhanced coronary artery smooth muscle cell proliferation, which was reduced by transfection with small interfering RNA duplexes targeted at Egr-1 mRNA. These effects required viable chlamydiae and depended on p44͞42 mitogen-activated protein kinase activity but not on the p38 mitogen-activated protein kinase pathway. Postinfectious Egr-1 mRNA up-regulation in arterial vessels was confirmed ex vivo in a rat aortic ring model of focal vascular chlamydial infection. An in vivo model based on the injection of C. pneumoniae-infected PBMCs into mice confirmed Egr-1 mRNA up-regulation within 24 h of endovascular infection. Arterial injury from repeated direct chlamydial infections and cell-to-cell contact with C. pneumoniae-infected PBMCs might represent a chronic focus of proliferative activity linked to the media proliferation seen in advanced atherosclerosis. Overall, chlamydial infection induces a proliferative phenotype in vascular cells via transcription factor Egr-1 activation in vitro, ex vivo, and in vivo.atherosclerosis ͉ cell proliferation T he comprehension of the pathogenesis of atherosclerosis has changed fundamentally. Models suggesting atherogenesis as a static accumulation of lipid-loaded macrophages and adherent thrombocytes were expanded by a more dynamic view of the mechanisms involved (1). Inflammation and proliferation of vascular smooth muscle cells were established as the central pathomechanisms (2), suggesting that injurious stimuli other than the known risk factors may initiate and trigger atherosclerosis. Epidemiological studies indicated that persistent infectious agents like Chlamydia (Chlamydophila) pneumoniae or herpesviruses might be involved in perpetuating coronary artery disease. Although diagnostic assays have produced controversial results on its frequency in vascular infection, C. pneumoniae remains the only replicative pathogen that has been recovered from atherosclerotic lesions, where it seems to be deposited by infected circulating blood monocytes (3-6). Vascular C. pneumoniae infection has recently been linked to the inflammatory and procoagulatory component of atherosclerosis by demonstrating small GTPase-mediated NF-B activation (7). Chlamydial heat-shock protein (8) and a soluble factor derived from infected endothelial cells are known to trigger smooth muscle cell proliferation (9). The molecular mechanisms leading to postinfectious proliferation of vascular cells, however, are unknown, although the entry into and the pro...

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Section: Discussionmentioning

confidence: 99%

“…Rat thoracic aortae were isolated under sterile conditions from Wistar rats. Surrounding tissue was removed, and the aortae were cut in 3-to 4-mm rings, as described (20). For infection experiments, aortic rings were cultivated in RPMI medium 1640 (Sigma) at 37°C in 5% CO 2 atmosphere.…”

Section: Methodsmentioning

confidence: 99%

Chlamydia pneumoniae infection promotes a proliferative phenotype in the vasculature through Egr-1 activation in vitro and in vivo

Rupp¹,

Hellwig-Bürgel²,

Wobbe³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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“…1 This response is best demonstrated in the neuro-endocrine system (eg, the hypothalamic-pituitary-adrenal axis) 2 and, in this setting, may be mediated by the activation of the glucocorticoid cascade 3 and of the sympathetic nervous system. 4,5 The restraint stress model often has been used to investigate the stress response experimentally in terms of pharmacologic, physiologic, or pathologic phenomena in vivo. 6 For example, restraint stress induces the expression of heat shock protein, a typical stress protein, in the rat, 2,4 and this induction may be mediated by the sympathetic nervous system.…”

Section: Introductionmentioning

confidence: 99%

“…6 For example, restraint stress induces the expression of heat shock protein, a typical stress protein, in the rat, 2,4 and this induction may be mediated by the sympathetic nervous system. 4,5 The induction of stress proteins may contribute to the development of a number of clinically relevant phenomena, including tissue and organ damage, and the immune response. 7 Hypercoagulability in the blood and thrombotic tendency also may be induced by physical 8,9 and mental stress.…”

Section: Introductionmentioning

confidence: 99%

Aging and obesity augment the stress-induced expression of tissue factor gene in the mouse

Yamamoto

Shimokawa

et al. 2002

Blood

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“…This response is best characterized in the neuro-endocrine system (e.g., the hypothalamic-pituitaryadrenal axis; ref. 10), and in this setting, may be mediated, at least in part, by the activation of the glucocorticoid cascade (11) and of the sympathetic nervous system (12,13).…”

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confidence: 99%

Plasminogen activator inhibitor-1 is a major stress-regulated gene: Implications for stress-induced thrombosis in aged individuals

Yamamoto

Takeshita

Shimokawa

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

148

127

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Plasminogen activator inhibitor-1 (PAI-1) is one of the primary inhibitors of the fibrinolytic system and has been implicated in a variety of thrombotic disorders. In this report, stress-induced changes in murine PAI-1 gene expression were investigated to study the role of this inhibitor in the development of stress-induced hypercoagulability. Restraint stress led to a dramatic induction of plasma PAI-1 antigen and of tissue PAI-1 mRNA with maximum induction in adipose tissues. In situ hybridization analysis of the stressed mice revealed that strong signals for PAI-1 mRNA were localized to hepatocytes, renal tubular epithelial cells, adrenomedullar chromaffin cells, neural cells in the paraaortic sympathetic ganglion, vascular smooth muscle cells, and adipocytes, but not to endothelial cells. These observations indicate that the stress induces the PAI-1 gene expression in a tissue-specific and cell type-specific manner. The induction of PAI-1 mRNA by restraint stress was greater than that observed for heat shock protein, a typical stress protein, suggesting that PAI-1 is one of the most highly induced stress proteins. Importantly, the magnitude of induction of PAI-1 mRNA by stress increased markedly with age, and this increase in PAI-1 correlated with tissue thrombosis in the older stressed mice. Moreover, much less tissue thrombosis was induced by restraint stress in young and aged PAI-1-deficient mice compared with agematched wild-type mice. These results suggest that the large induction of PAI-1 by stress increases the risk for thrombosis in the older populations, and that the adipose tissue may be involved.

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Activation of heat shock protein (hsp)70 and proto-oncogene expression by alpha1 adrenergic agonist in rat aorta with age.

Cited by 46 publications

References 42 publications

Chlamydia pneumoniae infection promotes a proliferative phenotype in the vasculature through Egr-1 activation in vitro and in vivo

Chlamydia pneumoniae infection promotes a proliferative phenotype in the vasculature through Egr-1 activation in vitro and in vivo

Aging and obesity augment the stress-induced expression of tissue factor gene in the mouse

Plasminogen activator inhibitor-1 is a major stress-regulated gene: Implications for stress-induced thrombosis in aged individuals

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