HSF1 and constitutively active HSF1 improve vascular endothelial function (heat shock proteins improve vascular endothelial function)

Uchiyama, Tsuyoshi; Atsuta, Hiroyuki; Utsugi, Toshihiro; Oguri, Mitsuhiko; Hasegawa, Akira; Nakamura, Toshio; Nakai, Asami; Nakata, Masao; Maruyama, Ikuro; Tomura, Hideaki; Okajima, Fumikazu; Tomono, Shoichi; Kawazu, Shoji; Nagai, Ryozo; Kurabayashi, Masahiko

doi:10.1016/j.atherosclerosis.2006.03.037

Cited by 63 publications

(47 citation statements)

References 31 publications

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“…Recent studies have indicated significant correlations between HSP90 and expression of NOS (Sud et al 2007), and interestingly, a synergistic induction of NOS expression by HSP70 and HSP90 has recently been demonstrated in human endothelial cells (Uchiyama et al 2007). A further step in the current investigations is to determine the effect of simulated diving on NOS, the enzyme responsible for the production of NO, and the direct relation to the HSP70, HSP90, and glutathione.…”

Section: Discussionmentioning

confidence: 87%

Simulated diving after heat stress potentiates the induction of heat shock protein 70 and elevates glutathione in human endothelial cells

Djurhuus

Nossum

Lundsett

et al. 2010

Cell Stress and Chaperones

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Heat stress prior to diving has been shown to confer protection against endothelial damage due to decompression sickness. Several lines of evidence indicate a relation between such protection and the heat shock protein (HSP)70 and HSP90 and the major cellular red-ox determinant, glutathione (GSH). The present study has used human endothelial cells as a model system to investigate how heat stress and simulated diving affect these central cellular defense molecules. The results demonstrated for the first time that a simulated dive at 2.6 MPa (26 bar) had a potentiating effect on the heat-induced expression of HSP70, increasing the HSP70 concentration on average 54 times above control level. In contrast, a simulated dive had no significant potentiating effect on the HSP90 level, which might be due to the higher baseline level of HSP90. Both 2 and 24-h dive had similar effects on the HSP70 and HSP90, suggesting that the observed effects were independent of duration of the dive. The rapid HSP response following a 2-h dive with a decompression time of 5 min might suggest that the effects were due to compression or pressure per se rather than decompression and may involve posttranslational processing of HSP. The exposure order seemed to be critical for the HSP70 response supporting the suggestion that the potentiating effect of dive was not due to de novo synthesis of HSP70. Neither heat shock nor a simulated dive had any significant effect on the intracellular GSH level while a heat shock and a subsequent dive increased the total GSH level approximately 62%. Neither of these conditions seemed to have any effect on the GSH red-ox status.

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Section: Discussionmentioning

confidence: 87%

Simulated diving after heat stress potentiates the induction of heat shock protein 70 and elevates glutathione in human endothelial cells

Djurhuus

Nossum

Lundsett

et al. 2010

Cell Stress and Chaperones

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“…Rü cker et al (41) demonstrated that heat shock increased the expression of PAI-1 in vascular tissue of rat muscle. Uchiyama et al (42) reported that adenovirus vector-mediated overexpression of HSF1 gene reduced PAI-1 expression in cultured arterial endothelial cells, but the finding was not verified using any gene knockdown approach. The present study provided multiple lines of evidence for the involvement of HSF1 in glycated LDL-induced upregulation of PAI-1 in endothelial cells, including the inhibition of PAI-1 expression in arterial or venous endothelial cells by HSF1 siRNA and the suppression of PAI-1 promoter activity via mutagenesis of a HSE homolog in the PAI-1 promoter.…”

Section: Hsf1 In Glycated Ldl-induced Pai-1mentioning

confidence: 98%

Involvement of Heat Shock Factor-1 in Glycated LDL–Induced Upregulation of Plasminogen Activator Inhibitor-1 in Vascular Endothelial Cells

Zhao

Shen²

2007

Diabetes

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Coronary artery disease is the predominant cause of death in diabetic patients. Plasminogen activator inhibitor-1 (PAI-1) is the major physiological inhibitor of plasminogen activators. Heat shock protein (Hsp) was upregulated in uncontrolled diabetic patients. Our previous studies demonstrated that glycated LDL stimulated the generation of PAI-1 from vascular endothelial cells. The present study examined the effect of glycated LDL on the expression of heat shock factor-1 (HSF1), a physiological transcription factor of Hsp, and the involvement of HSF-1 in glycated LDL-induced production of PAI-1 in cultured human umbilical vein endothelial cells ( T he incidence of diabetes in North America has rapidly increased during the last three decades, and the trend is expected to continue (1). The most common cause of death in diabetic patients is coronary artery disease (CAD). Acute coronary syndrome is often associated with thrombosis at the lesions of atherosclerotic plaques (2,3). Thrombogenesis depends on an imbalance between coagulation and fibrinolysis in local blood circulation. Attenuated fibrinolytic activity has been detected in peripheral circulation of type 1 or type 2 diabetic patients (4,5). Plasminogen activator inhibitor-1 (PAI-1) is the major physiological inhibitor for fibrinolysis, which modulates the activity of tissue and urokinase plasminogen activators on the formation of plasmin. PAI-1 is also implicated in inflammation, endothelial dysfunction, and extracellular matrix remodeling (6). An elevated level of PAI-1 in plasma has been considered as a nontraditional risk factor for CAD and a marker of endothelial dysfunction (7).Hyperglycemia and dyslipoproteinemia are two major biochemical markers of diabetes. Elevated LDL is a classical risk factor for atherosclerotic cardiovascular disease. LDL clearance via the LDL receptor is attenuated by glycation (8). Elevated levels of small, dense LDL and glycated LDL were frequently detected in diabetic patients (9 -11). Previous studies in our laboratory demonstrated that glycated LDL increased the production of PAI-1 in cultured venous or arterial endothelial cells. LDL isolated from diabetic patients or glycated LDL modified in vitro enhanced the activity of PAI-1 promoter in endothelial cells (12)(13)(14)(15). Glycated LDL stimulated the generation of reactive oxygen species (ROS) and decreased the abundance of reduced glutathione in endothelial cells (16). The findings imply that glycated LDL may induce oxidative stress in vasculature. Heat shock, mechanical shear, or oxidative stress induces stress responses in cells, which are mediated by heat shock proteins (Hsps). The transcription of Hsp is mediated by heat shock factor (HSF) (17). HSF1 is the most widely distributed form of HSF in human body (18 -20). The activation of HSF1 is detected during embryo growth (21) or in diet-induced atherosclerotic animal models (22). The levels of Hsp-70 were increased in the peripheral circulation of diabetic patients with ketoacidosis (23). Neither the impact of ...

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“…HSPs are generally considered protective (1829). Indeed, an increase in HSP90, with its ability to stimulate eNOS, is considered one of the pleiotropic beneficial effects of statins (557).…”

Section: Er Stress In Endothelial Cellsmentioning

confidence: 99%

Molecular Biology of Atherosclerosis

Hopkins

2013

Physiological Reviews

382

344

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At least 468 individual genes have been manipulated by molecular methods to study their effects on the initiation, promotion, and progression of atherosclerosis. Most clinicians and many investigators, even in related disciplines, find many of these genes and the related pathways entirely foreign. Medical schools generally do not attempt to incorporate the relevant molecular biology into their curriculum. A number of key signaling pathways are highly relevant to atherogenesis and are presented to provide a context for the gene manipulations summarized herein. The pathways include the following: the insulin receptor (and other receptor tyrosine kinases); Ras and MAPK activation; TNF-␣ and related family members leading to activation of NF-B; effects of reactive oxygen species (ROS) on signaling; endothelial adaptations to flow including G protein-coupled receptor (GPCR) and integrin-related signaling; activation of endothelial and other cells by modified lipoproteins; purinergic signaling; control of leukocyte adhesion to endothelium, migration, and further activation; foam cell formation; and macrophage and vascular smooth muscle cell signaling related to proliferation, efferocytosis, and apoptosis. This review is intended primarily as an introduction to these key signaling pathways. They have become the focus of modern atherosclerosis research and will undoubtedly provide a rich resource for future innovation toward intervention and prevention of the number one cause of death in the modern world.

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HSF1 and constitutively active HSF1 improve vascular endothelial function (heat shock proteins improve vascular endothelial function)

Cited by 63 publications

References 31 publications

Simulated diving after heat stress potentiates the induction of heat shock protein 70 and elevates glutathione in human endothelial cells

Simulated diving after heat stress potentiates the induction of heat shock protein 70 and elevates glutathione in human endothelial cells

Involvement of Heat Shock Factor-1 in Glycated LDL–Induced Upregulation of Plasminogen Activator Inhibitor-1 in Vascular Endothelial Cells

Molecular Biology of Atherosclerosis

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