Cell Biology and Toxicology

, Volume 26, Issue 3, pp 215–223

Hsp70 expression in monocytes from patients with peripheral arterial disease and healthy controls

Monocyte Hsp70 in PAD
  • Jacqueline Madden
  • Jenifer C. Coward
  • Cliff P. Shearman
  • Robert F. Grimble
  • Philip C. Calder
Article

Abstract

Background

Heat shock proteins (HSP) are induced during cellular stress. Their role is to chaperone cellular proteins giving protection from denaturation and ultimately preventing cell death. Monocytes are key cells involved in atherosclerosis and are highly responsive to HSP induction. Therefore, we wished to examine monocyte Hsp70 expression and induction in patients with peripheral arterial disease (PAD) and in healthy controls.

Methods

We measured cellular Hsp70 levels in freshly isolated monocytes and released Hsp70 levels in plasma and monocyte culture supernatants, obtained from patients with PAD and from healthy controls. We assessed the effect of statin therapy on Hsp70 levels and examined monocyte cell survival in culture with and without immunological stress.

Results

Monocyte cellular Hsp70 was lower in patients with PAD compared to healthy controls (11.3 ± 7.4 ng/106 cells vs 20.7 ± 16.0 ng/106 cells; p < 0.001). Individuals on statin therapy from both PAD and control groups had lower monocyte Hsp70 compared to those not treated with statins. Concentrations of Hsp70 released into culture supernatants were not dependent on PAD or statin therapy. Cell survival was inversely associated with Hsp70 concentrations in culture supernatants but had no association with cellular concentrations of Hsp70.

Conclusions

Cellular Hsp70 and released Hsp70 may play different roles in monocyte health. Whilst induced Hsp70 destined for release appears to be unaffected in PAD, mechanisms responsible for cellular retention of Hsp70 may provide an area for future therapeutic targets in vascular disease.

Keywords

Cell survival Hsp70 Monocyte PAD Statin Inflammation 

Abbreviations

PAD

Peripheral arterial disease

Hsp70

Heat shock protein 70

ABPI

Ankle brachial pressure index

CRP

C-reactive protein

References

  1. Acheampong E, Parveen Z, Mengistu A, Ngoubilly N, Wigdahl B, Lossinsky AS, et al. Cholesterol-depleting statin drugs protect postmitotically differentiated human neurons against ethanol- and human immunodeficiency virus type 1-induced oxidative stress in vitro. J Virol. 2007;81:1492–501.CrossRefPubMedGoogle Scholar
  2. Bhatnagar D, Soran H, Durrington PN. Hypercholesterolaemia and its management. BMJ. 2008;337:a993.CrossRefPubMedGoogle Scholar
  3. Bobryshev YV, Lord RS. Expression of heat shock protein-70 by dendritic cells in the arterial intima and its potential significance in atherogenesis. J Vasc Surg. 2002;35:368–75.CrossRefPubMedGoogle Scholar
  4. Burg MB, Ferraris JD, Dmitrieva NI. Cellular response to hyperosmotic stresses. Physiol Rev. 2007;87:1441–74.CrossRefPubMedGoogle Scholar
  5. Chan YC, Shukla N, Abdus-Samee M, Berwanger CS, Stanford J, Singh M, et al. Anti-heat-shock protein 70 kDa antibodies in vascular patients. Eur J Vasc Endovasc Surg. 1999;18:381–5.CrossRefPubMedGoogle Scholar
  6. Dezfulian C, Raat N, Shiva S, Gladwin MT. Role of the anion nitrite in ischemia-reperfusion cytoprotection and therapeutics. Cardiovasc Res. 2007;75:327–38.CrossRefPubMedGoogle Scholar
  7. Giffard RG, Han RQ, Emery JF, Duan M, Pittet JF. Regulation of apoptotic and inflammatory cell signaling in cerebral ischemia: the complex roles of heat shock protein 70. Anesthesiology. 2008;109:339–48.CrossRefPubMedGoogle Scholar
  8. Gonzalez FM, Shiva S, Vincent PS, Ringwood LA, Hsu LY, Hon YY, et al. Nitrite anion provides potent cytoprotective and antiapoptotic effects as adjunctive therapy to reperfusion for acute myocardial infarction. Circulation. 2008;117:2986–94.CrossRefPubMedGoogle Scholar
  9. Hu S, Ciancio MJ, Lahav M, Fujiya M, Lichtenstein L, Anant S, et al. Translational inhibition of colonic epithelial heat shock proteins by IFN-gamma and TNF-alpha in intestinal inflammation. Gastroenterology. 2007;133:1893–904.CrossRefPubMedGoogle Scholar
  10. Karaflou M, Lambrinoudaki I, Christodoulakos G. Apoptosis in atherosclerosis: a mini-review. Mini Rev Med Chem. 2008;8:912–8.CrossRefPubMedGoogle Scholar
  11. Liu Y, Lehmann M, Baur C, Storck M, Sunder-Plassmann L, Steinacker JM. Hsp70 expression in skeletal muscle of patients with peripheral arterial occlusive disease. Eur J Vasc Endovasc Surg. 2002;24:269–73.CrossRefPubMedGoogle Scholar
  12. Liu JC, He M, Wan L, Cheng XS. Heat shock protein 70 gene transfection protects rat myocardium cell against anoxia-reoxygeneration injury. Chin Med J. 2007;120:578–83.PubMedGoogle Scholar
  13. Mehta TA, Greenman J, Ettelaie C, Venkatasubramaniam A, Chetter IC, McCollum PT. Heat shock proteins in vascular disease—a review. Eur J Vasc Endovasc Surg. 2005;29:395–402.PubMedGoogle Scholar
  14. Mestril R, Dillmann WH. Heat shock proteins and protection against myocardial ischemia. J Mol Cell Cardiol. 1995;27:45–52.CrossRefPubMedGoogle Scholar
  15. Moseley P. Stress proteins and the immune response. Immunopharmacology. 2000;48:299–302.CrossRefPubMedGoogle Scholar
  16. Pirillo A, Jacoviello C, Longoni C, Radaelli A, Catapano AL. Simvastatin modulates the heat shock response and cytotoxicity mediated by oxidized LDL in cultured human endothelial smooth muscle cells. Biochem Biophys Res Commun. 1997;231:437–41.CrossRefPubMedGoogle Scholar
  17. Ross R. Atherosclerosis—an inflammatory disease. N Engl J Med. 1999;340:115–26.CrossRefPubMedGoogle Scholar
  18. Wang X, Tokuda H, Hatakeyama D, Hirade K, Niwa M, Ito H, et al. Mechanism of simvastatin on induction of heat shock protein in osteoblasts. Arch Biochem Biophys. 2003;415:6–13.CrossRefPubMedGoogle Scholar
  19. Wright BH, Corton JM, El-Nahas AM, Wood RF, Pockley AG. Elevated levels of circulating heat shock protein 70 (Hsp70) in peripheral and renal vascular disease. Heart Vessels. 2000;15:18–22.CrossRefPubMedGoogle Scholar
  20. Zhang PL, Lun M, Schworer CM, Blasick TM, Masker KK, Jones JB, et al. Heat shock protein expression is highly sensitive to ischemia-reperfusion injury in rat kidneys. Ann Clin Lab Sci. 2008;38:57–64.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Jacqueline Madden
    • 1
  • Jenifer C. Coward
    • 1
  • Cliff P. Shearman
    • 1
  • Robert F. Grimble
    • 1
  • Philip C. Calder
    • 1
  1. 1.Institute of Human Nutrition, School of MedicineUniversity of SouthamptonSouthamptonUK

Personalised recommendations