Differential Distribution of 70-kD Heat Shock Protein in Atherosclerosis

Ad, Johnson; Pa, Berberian; Tytell, Michael; Mg, Bond

doi:10.1161/01.atv.15.1.27

Cited by 86 publications

(55 citation statements)

References 46 publications

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“…Clearly, a cytoprotective intracellular effect of HSP and a pro-inflammatory extracellular effect makes serum levels of HSPs difficult to interpret. HSP70 has been detected in both fibrotic and necrotic atherosclerotic plaques [23] and macrophages are an important source of HSP70 production in atherosclerotic plaques [24,25]. These immunohistochemical analysis clearly demonstrate that local expression of HSP70 within the atherosclerotic plaque occurs, however, it is unknown if the HSP70 is intracellular or extracellular.…”

Section: Discussionmentioning

confidence: 90%

Major role of HSP70 as a paracrine inducer of cytokine production in human oxidized LDL treated macrophages

et al. 2006

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Lipid accumulation and inflammation are key hallmarks of the atherosclerotic plaque and macrophage uptake of oxidized low-density lipoprotein (oxLDL) is believed to drive these processes. Initial experiments show that supernatants from oxLDL treated macrophages could induce IL-1β production in naïve macrophages. To search for potential paracrine mediators that could mediate this effect a DNA microarray scan of oxLDL treated human macrophages was performed. This analysis revealed that oxLDL induced activation of heat shock protein (HSP) expression. HSPs have been implicated in the development of atherosclerosis, but the exact mechanisms for this is unclear. Extracellular heat shock protein 70 (HSP70) has been shown to elicit a pro-inflammatory cytokine response in monocytes and could therefore be a potential paracrine pro-inflammatory mediator. After 24 h of oxLDL treatment there was a significant increase of HSP70 concentrations in supernatants from oxLDL treated macrophages (oxLDLsup) compared to untreated controls (P < 0.05). OxLDLsup could induce both interleukin (IL)-1β and IL-12 secretion in naïve macrophages. We also demonstrate that the effect of oxLDLsup on cytokine production and release could be blocked by inhibition of HSP70 transcription or secretion or by the use of HSP70 neutralizing antibodies. This suggests that extracellular HSP70 can mediate pro-inflammatory changes in macrophages in response to oxLDL.

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Section: Discussionmentioning

confidence: 90%

Major role of HSP70 as a paracrine inducer of cytokine production in human oxidized LDL treated macrophages

et al. 2006

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“…Whether such receptors exist and bind Hsp70 in neurons has not been investigated. However, in addition to such receptor-mediated activity, there is evidence that HSP70 can be internalized and readily imported into both cytoplasmic and nuclear compartments of arterial smooth muscle cells, U937 cells, lymphocytes, retinal ganglion cells, and neuroblastoma cells (Johnson et al, 1990(Johnson et al, , 1995Guzhova et al, 1998;Fujihara and Nadler, 1999;Guzhova et al, 2001;Yu et al, 2001). Administration of e-rhHsp70 reduces the number of dying motoneurons in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…In both arterial smooth muscle cells in culture and retinal ganglion cells in vivo, extracellular Hsc/Hsp70 promoted survival after nutrient deprivation or light damage, respectively (Johnson et al, 1995;Yu et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…Although the best understood role of HSP70 relates to its intracellular functions, secretion or release of HSP70 by one cell population to act on neighboring cells has been suggested (Tytell et al, 1986;Hightower and Guidon, 1989;Guzhova et al, 2001). Although it is unclear how extracellular Hsps function, there is evidence that they can be internalized and readily imported into both cytoplasmic and nuclear compartments of many cell types and that they appear to promote survival (Johnson et al, 1990(Johnson et al, , 1995Houenou et al, 1996;Guzhova et al, 1998;Fujihara and Nadler, 1999;Yu et al, 2001;Tidwell et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Extracellular Heat Shock Protein 70: A Critical Component for Motoneuron Survival

Robinson¹,

Tidwell²,

Gould³

et al. 2005

J. Neurosci.

111

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The dependence of developing spinal motoneuron survival on a soluble factor(s) from their target, muscle tissue is well established both in vivo and in vitro. Considering this apparent dependence, we examined whether a specific component of the stress response mediates motoneuron survival in trophic factor-deprived environments. We demonstrate that, although endogenous expression of heat shock protein 70 (HSP70) did not change during trophic factor deprivation, application of e-rhHsp70 (exogenous recombinant human Hsp70) promoted motoneuron survival. Conversely, depletion of HSP70 from chick muscle extract (MEx) potently reduces the survivalpromoting activity of MEx. Additionally, exogenous treatment with or spinal cord overexpression of Hsp70 enhances motoneuron survival in vivo during the period of naturally occurring cell death [programmed cell death (PCD)]. Hindlimb muscle cells and lumbar spinal astrocytes readily secrete HSP70 in vitro, suggesting potential physiological sources of extracellular Hsp70 for motoneurons. However, in contrast to exogenous treatment with or overexpression of Hsp70 in vivo, muscle-targeted injections of this factor in an ex vivo preparation fail to attenuate motoneuron PCD. These data (1) suggest that motoneuron survival requirements may extend beyond classical trophic factors to include HSP70, (2) indicate that the source of this factor is instrumental in determining its trophic function, and (3) may therefore influence therapeutic strategies designed to increase motoneuron Hsp70 signaling during disease or injury.

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“…40 Enhanced HSP70 protein levels protect against lethal heat stress and ischemia. 41 ROS such as H 2 O 2 have pleiomorphic effects on cells, eliciting apoptosis in some cell types 42 while stimulating early growth-response gene expression and proliferation in others.…”

Section: Discussionmentioning

confidence: 99%

Reactive Oxygen Species Regulate Heat-Shock Protein 70 via the JAK/STAT Pathway

Madamanchi

Patterson

et al. 2001

ATVB

210

150

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Abstract-Reactive oxygen species (ROS) such as hydrogen peroxide (H 2 O 2 ) activate intracellular signal transduction pathways implicated in the pathogenesis of cardiovascular disease. H 2 O 2 is a mitogen for rat vascular smooth muscle cells (VSMCs), and protein tyrosine phosphorylation is a critical event in VSMC mitogenesis. Therefore, we investigated whether the mitogenic effects of H 2 O 2 , such as stimulation of extracellular signal-regulated kinase (ERK)2, are mediated via activation of cytoplasmic Janus tyrosine kinases (JAKs). JAK2 was activated rapidly in VSMCs treated with H 2 O 2 , and signal transducers and activators of transcription (STAT) STAT1 and STAT3 were tyrosine-phosphorylated and translocated to the nucleus in a JAK2-dependent manner. A ccumulating evidence supports a critical role for oxidative stress in the pathogenesis of atherosclerosis, cancer, and other human diseases. 1 High levels of reactive oxygen species (ROS) damage DNA and inactivate proteins, 2 resulting in chronic cellular dysfunction. Many cell types have also harnessed ROS, albeit in lower concentrations, as intracellular signaling molecules to mediate growth factor and cytokine responses. 3,4 Modulation of growth responses by ROS has been demonstrated in a number of cell types, including vascular smooth muscle cells (VSMCs). 5,6 Stimulation of VSMC proliferation by ROS is thought to be a critical step in atherosclerotic lesion formation. 7 Tyrosine phosphorylation of cellular proteins and the consequent induction of transcription of early-response genes are key determinants of cell growth and differentiation in response to mitogenic signaling. 8 VSMC mitogens such as platelet-derived growth factor and epidermal growth factor activate receptor protein tyrosine kinases on binding, which stimulate intracellular signaling pathways that result in mitogen-activated protein kinase activation. 9,10 Other mitogens, such as thrombin and angiotensin II, activate G proteincoupled receptors that do not possess intrinsic tyrosine kinase activity but require tyrosine phosphorylation events to induce mitogenesis. [11][12][13] The necessary role for protein tyrosine phosphorylation in mitogenesis elicited by thrombin and ROS indicates that these mitogens may utilize cytoplasmic protein tyrosine kinases in their signaling cascade. Forming 1 such group of tyrosine kinases are Janus kinases (JAKs), which along with their substrates, signal transducers and activators of transcription (STATs), have hitherto been characterized as essential mediators of cytokine and polypeptide hormone-induced signaling. 8,14 Members of the JAK/STAT pathway mediate at least some biological effects of angiotensin II, 15 plateletderived growth factor-BB, 15,16 and endothelial growth factor. 17 Activation of the JAK/STAT pathway has also been observed in response to generation of intracellular ROS 18 and exogenous hydrogen peroxide (H 2 O 2 ). 19 On phosphorylation by JAKs of tyrosine residues, activated STAT dimers translocate to the nucleus to transactivate tar...

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Differential Distribution of 70-kD Heat Shock Protein in Atherosclerosis

Cited by 86 publications

References 46 publications

Major role of HSP70 as a paracrine inducer of cytokine production in human oxidized LDL treated macrophages

Major role of HSP70 as a paracrine inducer of cytokine production in human oxidized LDL treated macrophages

Extracellular Heat Shock Protein 70: A Critical Component for Motoneuron Survival

Reactive Oxygen Species Regulate Heat-Shock Protein 70 via the JAK/STAT Pathway

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