HOME SUBSCRIPTIONS CURRENT ISSUE PAST ISSUES CARDIOSOURCE SEARCH HELP FEEDBACK		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by George, J. Articles by Keren, G. Search for Related Content PubMed PubMed Citation Articles by George, J. Articles by Keren, G.

EXPERIMENTAL STUDY

Accelerated intimal thickening in carotid arteries of balloon-injured rats after immunization against heat shock protein 70

Jacob George, MD^*, Shai Greenberg, MSc^*, Iris Barshack, MD, Madhavir Singh, PhD, Sara Pri-Chen, PhD^*, Shlomo Laniado, MD^* and Gad Keren, MD^*,*

^* Department of Cardiology and the Cardiovascular Research Laboratory, Tel Aviv Medical Center, Tel Aviv, Israel
Institute of Pathology, Sheba Medical Center, Tel Hashomer, Israel
GBF-Braunschweig, Braunschweig, Germany

Manuscript received December 19, 2000; revised manuscript received June 14, 2001, accepted July 12, 2001.

^* Reprint requests and correspondence: Dr. Gad Keren, Department of Cardiology and the Cardiovascular Research Laboratory, Ichilov Hospital, Elias Sourasky, Tel Aviv Medical Center, 6 Weizman Street, Tel Aviv, Israel
kereng{at}tasmc.health.gov.il

OBJECTIVES

The goal of this study was to test the hypothesis that induction of an immune response to heat shock protein (Hsp) 70 would increase intimal thickening in a rat carotid-injury model.

BACKGROUND

Restenosis resulting from intimal thickening poses a major limitation to the long-term success of coronary angioplasty. Several studies have proposed that infectious agents increase restenosis. Heat shock proteins are highly conserved structures, produced by all cells in response to nonspecific forms of stress. Infectious agents are known to contain Hsp70, which is markedly immunogenic and can elicit a strong immune response.

METHODS

To investigate whether Hsp70 immunity can affect neointimal thickening, we immunized rats with either Hsp70 (n = 11), bovine serum albumin ([BSA] n = 9) or with a control adjuvant (n = 10). Three weeks later, rats were boosted using the same regimen to achieve a sustained immune response to Hsp70 after which carotid injury was applied to all animals.

RESULTS

Arterial injury was associated with upregulation of Hsp70, 3, 7 and 14 days after induction of the injury as evidenced by Western blotting and immunohistochemistry. Intimal area and intimal/medial ratio was significantly increased in Hsp70-immunized rats in comparison with BSA or control-injected rats.

CONCLUSIONS

Our results imply that upregulation of Hsp70 in balloon-injured arteries can serve as a target for anti-Hsp70 immune response, thereby facilitating enhanced intimal thickening. These observations may provide a possible mechanism that explains the accelerated intimal thickening that has been associated with the occurrence of infectious pathogens.

Abbreviations and Acronyms   BSA = bovine serum albumin   ELISA = enzyme-linked immunosorbent assay   Hsp = heat shock protein   IFA = incomplete Freund’s adjuvant   IgG = immunoglobulin G   PBS = phosphate-buffered saline   PI = protease inhibitor   SMC = smooth muscle cell   TBS = Tris-buffered saline

This article has been cited by other articles:

				C. Brasselet, E. Durand, F. Addad, F. Vitry, G. Chatellier, C. Demerens, M. Lemitre, R. Garnotel, D. Urbain, P. Bruneval, et al. Effect of local heating on restenosis and in-stent neointimal hyperplasia in the atherosclerotic rabbit model: a dose-ranging study Eur. Heart J., February 1, 2008; 29(3): 402 - 412. [Abstract] [Full Text] [PDF]

				A. Tincani, C. B. Rebaioli, M. Taglietti, and Y. Shoenfeld Heart involvement in systemic lupus erythematosus, anti-phospholipid syndrome and neonatal lupus Rheumatology, October 1, 2006; 45(suppl_4): iv8 - iv13. [Abstract] [Full Text] [PDF]

				A Tincani, C Biasini-Rebaioli, R Cattaneo, and P Riboldi Nonorgan specific autoantibodies and heart damage Lupus, September 1, 2005; 14(9): 656 - 659. [Abstract] [PDF]

				U. Hagg, M. E. Johansson, J. Gronros, A. S. Naylor, I. H. Jonsdottir, G. Bergstrom, P.-A. Svensson, and L.-m. Gan Gene expression profile and aortic vessel distensibility in voluntarily exercised spontaneously hypertensive rats: potential role of heat shock proteins Physiol Genomics, August 11, 2005; 22(3): 319 - 326. [Abstract] [Full Text] [PDF]

				M. Ghayour-Mobarhan, S. A New, D. J Lamb, B. J Starkey, C. Livingstone, T. Wang, N. Vaidya, and G. A Ferns Dietary antioxidants and fat are associated with plasma antibody titers to heat shock proteins 60, 65, and 70 in subjects with dyslipidemia Am. J. Clinical Nutrition, May 1, 2005; 81(5): 998 - 1004. [Abstract] [Full Text] [PDF]

				M. Ghayour-Mobarhan, D. J. Lamb, N. Vaidya, C. Livingstone, T. Wang, and G. A. A. Ferns Heat Shock Protein Antibody Titers Are Reduced by Statin Therapy in Dyslipidemic Subjects: A Pilot Study Angiology, January 1, 2005; 56(1): 61 - 68. [Abstract] [PDF]

				J. George, J. Sack, I. Barshack, P. Keren, I. Goldberg, R. Haklai, G. Elad-Sfadia, Y. Kloog, and G. Keren Inhibition of Intimal Thickening in the Rat Carotid Artery Injury Model by a Nontoxic Ras Inhibitor Arterioscler. Thromb. Vasc. Biol., February 1, 2004; 24(2): 363 - 368. [Abstract] [Full Text]