Heat shock protein-27 attenuates foam cell formation and atherogenesis by down-regulating scavenger receptor-A expression via NF-κB signaling

Raizman, Joshua E.; Chen, Yong Xiang; Seibert, Tara; Hibbert, Benjamin; Cuerrier, Charles M.; Salari, Samira; Zhao, Xiaoling; Hu, Tieqiang; Shi, Chunhua; Ma, Xiaochi; Simard, Trevor; Caravaggio, Justin W; Rayner, Katey J.; Bowdish, Dawn M. E.; Moore, Kathryn J.; O'Brien, Edward R.

doi:10.1016/j.bbalip.2013.07.015

Cited by 30 publications

(49 citation statements)

References 22 publications

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“…Functionally, hsp27 is a known potent anti-apoptotic protein (Ferns et al 2006, Ghayour-Mobarhan et al 2012, Vidyasagar et al 2012). Since apoptosis of vascular smooth muscle is involved in the weakening of the fibrous cap and therefore plaque rupture, the reduced expression of protective Hsp27 may favor the formation of unstable plaque (Ghayour-Mobarhan et al 2012, Vidyasagar et al 2012, Raizman et al 2013). In addition, Hsp27 has been implicated as a regulator of tissue inflammation, a pivotal process in atherosclerosis (Libby 2002).…”

Section: Discussionmentioning

confidence: 99%

“…It has been suggested that Hsp27 can lower the levels of the inflammatory cytokine IL-1β in macrophages and enhance extracellular levels of the anti-inflammatory cytokine interleukin-10 (IL-10) (De et al 2000, Rayner et al 2008). Extracellular Hsp27 can also attenuate foam cell formation and atherogenesis by down-regulating NF-κB signaling in macrophages (Raizman et al 2013, Salari et al 2013). However, it should be noted that a post-hoc analysis of our data did not find any significant correlation between circulating Hsp27 and the inflammatory related markers hsCRP or HDL-cholesterol.…”

Section: Discussionmentioning

confidence: 99%

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Plasma heat shock protein 27 is associated with coronary artery disease, abdominal aortic aneurysm and peripheral artery disease

et al. 2014

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Low protein levels of Hsp27 have been reported in atherosclerotic plaques. In addition, human studies have indicated that circulating Hsp27 levels are lower in coronary artery disease patients compared with controls. It remains, however, unclear whether this applies to other forms of atherosclerotic disease.Plasma Hsp27 from 280 subjects was examined by ELISA. The cohort included 80 coronary artery disease (CAD), 40 peripheral artery disease (PAD) and 80 abdominal aortic aneurysm (AAA) patients. Eighty elderly subjects, without any clinical history of vascular diseases, were used as a control group. Receiver operating curve (ROC) and logistic regression model analysis were performed to evaluate the potential value of Hsp27 as a circulating biomarker.Patients with atherosclerotic vascular diseases had significantly lower levels of Hsp27 than control subjects (p < 0.001). Moreover, Hsp27 was significantly lower in CAD patients than other atherosclerotic vascular disease groups (p < 0.001). There was no difference in Hsp27 levels between the AAA and PAD groups. Using the ROC-generated optimal cut-off values for Hsp27, logistic regression modeling indicated that low plasma Hsp27 was independently associated with the presence of multiple forms of atherosclerotic disease.In conclusion, circulating Hsp27 is significantly lower in patients with multiple forms of atherosclerotic arterial disease.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Plasma heat shock protein 27 is associated with coronary artery disease, abdominal aortic aneurysm and peripheral artery disease

et al. 2014

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“…Undoubtedly, thorough understanding of the underlying mechanisms and identification of novel targets will aid in curtailing CVD prevalence. Emerging evidence implicates sHSPs in the pathogenesis of CVD, and several studies uncovered mutations and single nucleotide polymorphisms in sHSP genes associated with cardiomyopathies (Martin et al 2014a;Martin et al 2014b;Raizman et al 2013;Rajasekaran et al 2007;Seibert et al 2013;Stark et al 2010;Vicart et al 1998). For instance, even a single point mutation of HSPB8 can cause cardiac disease (Sanbe et al 2013).…”

Section: Shsps In Cardiovascular Diseasementioning

confidence: 99%

“…It has been shown to reduce macrophage infiltration and free serum cholesterol and attenuate foam cell formation. This occurs via downregulation of scavenger receptor-A expression via NF-κB signalling and interaction with toll-like receptors (TLRs) in both cardiovascular and immune cells inter allia (Batulan et al 2016;Jin et al 2014;Raizman et al 2013). Secreted sHSPs are now considered potential therapeutic agents to prevent or ameliorate inflammatory processes (van Noort et al 2012).…”

Section: Extracellular Shsps In Cvd and Inflammationmentioning

confidence: 99%

Small heat shock proteins in ageing and age-related diseases

Charmpilas

Kyriakakis

Tavernarakis

2017

Cell Stress and Chaperones

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Small heat shock proteins (sHSPs) are gatekeepers of cellular homeostasis across species, preserving proteome integrity under stressful conditions. Nonetheless, recent evidence suggests that sHSPs are more than molecular chaperones with merely auxiliary role. In contrast, sHSPs have emerged as central lifespan determinants, and their malfunction has been associated with the manifestation of neurological disorders, cardiovascular disease and cancer malignancies. In this review, we focus on the role of sHSPs in ageing and ageassociated diseases and highlight the most prominent paradigms, where impairment of sHSP function has been implicated in human pathology.

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“…Although the role of NF‐kB activation in atherosclerosis is complex and depends on the context and/ or dynamic stage of disease, as well as the local milieu of cytokines, there are important downstream transcriptional events when HSP‐27 activates macrophage NF‐kB. In particular, we detected a dramatic increase in granulocyte monocyte colony stimulating factor (GM‐CSF) expression (~2000‐fold) and secretion (3, 5). GM‐CSF is a myeloid factor that is abundant in atherosclerotic plaques and enhances dendritic cell (DC) differentiation (8, 9).…”

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confidence: 89%

Heat shock protein 27–derived atheroprotection involves reverse cholesterol transport that is dependent on GM‐CSF to maintain ABCA1 and ABCG1 expression in ApoE ⁻ / ⁻ mice.

et al. 2017

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Recently, we demonstrated that heat shock protein (HSP)-27 is protective against the development of experimental atherosclerosis, reducing plaque cholesterol content by more than 30%. Moreover, elevated HSP-27 levels are predictive of relative freedom from clinical cardiovascular events. HSP-27 signaling occurs the activation of NF-κB, which induces a marked up-regulation in expression of granulocyte-monocyte colony-stimulating factor (GM-CSF), a cytokine that is known to alter ABC transporters involved in reverse cholesterol transport (RCT). Therefore, we hypothesized that HSP-27-derived GM-CSF has a potent role in impeding plaque formation by promoting macrophage RCT and sought to better characterize this pathway. Treatment of THP-1 cells, RAW-Blue cells, and primary macrophages with recombinant HSP-27 resulted in NF-κB activation TLR-4 and was inhibited by various pharmacologic blockers of this pathway. Moreover, HSP-27-induced upregulation of GM-CSF expression was dependent on TLR-4 signaling. Recombinant (r)HSP-27 treatment of ApoE female (but not male) mice for 4 wk yielded reductions in plaque area and cholesterol clefts of 33 and 47%, respectively, with no effect on GM-CSFApoE mice. With 12 wk of rHSP-27 treatment, both female and male mice showed reductions in plaque burden (55 and 42%, respectively) and a 60% reduction in necrotic core area but no treatment effect in GM-CSFApoE mice. functional studies revealed that HSP-27 enhanced the expression of ABCA1 and ABCG1, as well as facilitated cholesterol efflux by ∼10%. These novel findings establish a paradigm for HSP-27-mediated RCT and set the stage for the development of HSP-27 atheroprotective therapeutics.-Pulakazhi Venu, V. K., Adijiang, A., Seibert, T., Chen, Y.-X., Shi, C., Batulan, Z., O'Brien, E. R. Heat shock protein 27-derived atheroprotection involves reverse cholesterol transport that is dependent on GM-CSF to maintain ABCA1 and ABCG1 expression in ApoE mice.

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Heat shock protein-27 attenuates foam cell formation and atherogenesis by down-regulating scavenger receptor-A expression via NF-κB signaling

Cited by 30 publications

References 22 publications

Plasma heat shock protein 27 is associated with coronary artery disease, abdominal aortic aneurysm and peripheral artery disease

Plasma heat shock protein 27 is associated with coronary artery disease, abdominal aortic aneurysm and peripheral artery disease

Small heat shock proteins in ageing and age-related diseases

Heat shock protein 27–derived atheroprotection involves reverse cholesterol transport that is dependent on GM‐CSF to maintain ABCA1 and ABCG1 expression in ApoE ⁻ / ⁻ mice.

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Heat shock protein-27 attenuates foam cell formation and atherogenesis by down-regulating scavenger receptor-A expression via NF-κB signaling

Cited by 30 publications

References 22 publications

Plasma heat shock protein 27 is associated with coronary artery disease, abdominal aortic aneurysm and peripheral artery disease

Plasma heat shock protein 27 is associated with coronary artery disease, abdominal aortic aneurysm and peripheral artery disease

Small heat shock proteins in ageing and age-related diseases

Heat shock protein 27–derived atheroprotection involves reverse cholesterol transport that is dependent on GM‐CSF to maintain ABCA1 and ABCG1 expression in ApoE − / − mice.

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Heat shock protein 27–derived atheroprotection involves reverse cholesterol transport that is dependent on GM‐CSF to maintain ABCA1 and ABCG1 expression in ApoE ⁻ / ⁻ mice.