In vivo imaging of the effect of LPS on arterial endothelial cells: molecular imaging of heat shock protein 60 expression

Wick, Marius C.; Mayerl, Christina; Backović, Aleksandar; Zee, Ruurd van der; Jaschke, Werner; Dietrich, Hermann; Wick, Georg

doi:10.1007/s12192-008-0044-2

Cited by 27 publications

(14 citation statements)

References 63 publications

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“…These might include the inherent anti-inflammatory properties of Hsp70 and/or its direct effects on the biology and functional status of endothelial cells. The development of new molecular imaging techniques that are capable of imaging endothelial-expressed proteins such as Hsp60 (HSPD1) in vivo (Wick et al 2008) might also provide new insight into real-time stress protein-endothelial interactions. In summary, studies are now revealing new mechanistic insights into the apparent atheroprotective effects of extracellular Hsp70, and these are likely to result in the development of new approaches for predicting the development and progression of cardiovascular disease and novel therapeutic strategies for its effective management.…”

Section: Resultsmentioning

confidence: 99%

The atheroprotective properties of Hsp70: a role for Hsp70-endothelial interactions?

Pockley

Calderwood

Multhoff

2009

Cell Stress and Chaperones

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Although heat shock (stress) proteins are typically regarded as being exclusively intracellular molecules, it is now apparent that they can be released from cells in the absence of cellular necrosis. We and others have reported the presence of Hsp60 (HSPD1) and Hsp70 (HSPA1A) in the circulation of normal individuals and our finding that increases in carotid intima-media thicknesses (a measure of atherosclerosis) in subjects with hypertension at a 4-year follow-up are less prevalent in those having high serum Hsp70 (HSPA1A) levels at baseline suggests that circulating Hsp70 (HSPA1A) has atheroprotective effects. Given that circulating Hsp70 (HSPA1A) levels can be in the range which has been shown to elicit a number of biological effects in vitro, and our preliminary findings that Hsp70 (HSPA1A) binds to and is internalised by human endothelial cell populations, we speculate on the mechanisms that might be involved in the apparent atheroprotective properties of this protein.

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Section: Resultsmentioning

confidence: 99%

The atheroprotective properties of Hsp70: a role for Hsp70-endothelial interactions?

Pockley

Calderwood

Multhoff

2009

Cell Stress and Chaperones

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“…48 This process can be visualized in vitro and in vivo by molecular imaging techniques (Supplemental Figure I). 49…”

Section: Hsp In Atherosclerosismentioning

confidence: 99%

Heat Shock Protein 60 and Immune Inflammatory Responses in Atherosclerosis

Grundtman

Kreutmayer

Almanzar

et al. 2011

ATVB

Self Cite

168

144

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Abstract-Hallmarks of inflammation in various cardiovascular diseases, notably atherosclerosis, have been observed for a long time. However, evidence for an (auto)antigen-driven process at these sites of inflammation has come forward only recently. Heat shock proteins (HSPs) have been identified as playing either immunologically mediated disease promoting or protective roles. HSP60 has been shown to trigger innate and adaptive immune responses that initiate the earliest still reversible inflammatory stage of atherosclerosis. HSP60 is structurally highly conserved and abundantly expressed by prokaryotic and eukaryotic cells under stressful conditions. Beneficial protective immunity to microbial HSP60 acquired by infection or vaccination and bona fide autoimmunity to biochemically altered autologous HSP60 is present in all humans. In vitro and in vivo experiments have demonstrated that classical atherosclerosis risk factors can act as endothelial stressors that provoke the simultaneous expression of adhesion molecules and of HSP60 in mitochondria, in cytoplasm, and on the cell surface, where it acts as a "danger signal" for cellular and humoral immune reactions. Hence, protective, preexisting anti-HSP60 immunity may have to be "paid for" by harmful (auto)immune cross-reactive attack on arterial endothelial cells maltreated by atherosclerosis risk factors. These experimentally and clinically proven findings are the basis for the autoimmune concept of atherosclerosis. (Arterioscler Thromb Vasc Biol. 2011;31:960-968.)Key Words: atherosclerosis Ⅲ endothelium Ⅲ immune system Ⅲ risk factors Ⅲ stress Ⅲ heat shock protein T ypical cellular hallmarks of chronic inflammation and infections, notably infiltration by mononuclear cells, are also present in the cardiovascular system, as has been known for more than 150 years. However, until quite recently, it was not clear whether these inflammatory immunologic processes are primary or secondary in nature. 1 One of the reasons for this uncertainty may have been the fact that most investigations in humans were conducted on surgical or autopsy specimens representing very advanced stages of cardiovascular disease (CVD) and thus did not provide information on the initial mechanisms triggering these processes. In complex situations, such as in atherosclerosis, it was also difficult to appreciate that different, clinically well-proven risk factors may provoke a similar, or even identical, pathophysiological outcome. The main thrust to resolve this dilemma was to delineate the array of nonspecific and specific humoral and cellular inflammatory reactions taking place within the afflicted vascular territories. The availability of animal models that, at least partly, mimic human CVD was of utmost importance for this progress. In recent decades, the aim has been to identify exogenous or autologous antigens that may induce the local cardiovascular immune reactions. Among the candidates for such antigens are infectious agents, such as Chlamydia pneumoniae, as well as autoantigens, such as b...

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“…17.2a). Moreover the distribution of externalised HSP60 matches areas of atherosclerosis susceptibility [30]. Interestingly, the preferential distribution of macrophages into atherosclerosis-prone areas occurred not only in ApoE knockout mice but also, to a lesser extent, in the normocholesterolaemic C57bl6 background strain.…”

Section: Initiation Of Atherosclerosismentioning

confidence: 82%

Macrophages and Atherosclerosis

Newby

2011

Inflammation and Atherosclerosis

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In vivo imaging of the effect of LPS on arterial endothelial cells: molecular imaging of heat shock protein 60 expression

Cited by 27 publications

References 63 publications

The atheroprotective properties of Hsp70: a role for Hsp70-endothelial interactions?

The atheroprotective properties of Hsp70: a role for Hsp70-endothelial interactions?

Heat Shock Protein 60 and Immune Inflammatory Responses in Atherosclerosis

Macrophages and Atherosclerosis

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