© 1995 American Heart Association, Inc.
Articles |
Differential Distribution of 70-kD Heat Shock Protein in Atherosclerosis
Its Potential Role in Arterial SMC Survival
From the Department of Neurobiology and Anatomy, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC, and the Department of Atherosclerosis and Vascular Biology (P.A.B.), Sandoz Research Institute, East Hanover, NJ.
Correspondence to Dr A. Daniel Johnson, Texas Heart Institute, Vascular Cell Biology Laboratory, PO Box 20345, Mail Code 2-255, Houston, TX 77225.
Abstract Smooth muscle cell death may contribute to necrotic plaque rupture and subsequent thromboembolus. Stress-induced synthesis of heat-shock proteins (HSPs) normally protects cells from death, but vascular HSPs may become insufficient as cytotoxicity increases in advanced plaques. To determine whether vascular HSP content is altered near necrosis, we compared 70-kD HSP (HSP70) distribution between fibrotic and necrotic plaques in immunostained carotid endarterectomy specimens. Average levels of HSP70 immunoreactivity were compared by video densitometry between fibrotic and necrotic plaques or between their underlying media. Both necrotic plaques and their underlying media contained significantly more HSP70 staining than did fibrotic tissues. To test whether cellular HSP70 correlated with resistance to toxicity in vitro, aortic smooth muscle cells (aSMCs) were heat shocked to induce endogenous HSPs or given 2 to 50 µg/mL purified HSP70. Cells were then serum deprived or exposed to 12 to 96 µmol/L cholestanetriol (C3ol) or 25-hydroxycholesterol, and survival was determined. Cellular HSP70 content was assayed by immunoblotting, and protein synthesis was monitored by 35S radiolabeling. Serum deprivation inhibited general protein synthesis but induced HSP70; C3ol exposure inhibited both overall protein and HSP70 synthesis, including post–heat shock. Induction of endogenous HSPs or 10 µg/mL exogenous HSP70 improved viability of serum-deprived cells (P<.05 and P<.01, respectively), while only exogenous HSP70 protected against C3ol (P<.002). The results suggest that insufficient HSP70 accumulates in aSMCs residing near necrosis to protect against plaque toxicity; aSMC death might then occur, allowing resident macrophages to degrade and destabilize the matrix, leading to rupture.
Key Words: plaque necrosis • cytoprotection • HSP70 • stress response • smooth muscle cells
This article has been cited by other articles:
 |
|
 |
|
  M. Matsumoto, P. C. Dimayuga, C. Wang, J. Kirzner, M. Cercek, J. Yano, K.-Y. Chyu, P. K. Shah, and B. Cercek Exogenous heat shock protein-70 inhibits cigarette smoke-induced intimal thickening Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2008; 295(4): R1320 - R1327. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Herrmann, S. M. Soares, L. O. Lerman, and A. Lerman Potential Role of the Ubiquitin-Proteasome System in Atherosclerosis: Aspects of a Protein Quality Disease J. Am. Coll. Cardiol., May 27, 2008; 51(21): 2003 - 2010. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Martin-Ventura, M. C. Duran, L. M. Blanco-Colio, O. Meilhac, A. Leclercq, J.-B. Michel, O. N. Jensen, S. Hernandez-Merida, J. Tunon, F. Vivanco, et al. Identification by a Differential Proteomic Approach of Heat Shock Protein 27 as a Potential Marker of Atherosclerosis Circulation, October 12, 2004; 110(15): 2216 - 2219. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Han, Q. A. Truong, S. Park, and J. L. Breslow Two Hsp70 family members expressed in atherosclerotic lesions PNAS, February 4, 2003; 100(3): 1256 - 1261. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Patterson and D. Cyr Welcome to the Machine: A Cardiologist's Introduction to Protein Folding and Degradation Circulation, November 19, 2002; 106(21): 2741 - 2746. [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Xu Role of Heat Shock Proteins in Atherosclerosis Arterioscler. Thromb. Vasc. Biol., October 1, 2002; 22(10): 1547 - 1559. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. K. Kanwar, J. R. Kanwar, D. Wang, D. J. Ormrod, and G. W. Krissansen Temporal Expression of Heat Shock Proteins 60 and 70 at Lesion-Prone Sites During Atherogenesis in ApoE-Deficient Mice Arterioscler. Thromb. Vasc. Biol., December 1, 2001; 21(12): 1991 - 1997. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. George, S. Greenberg, I. Barshack, M. Singh, S. Pri-Chen, S. Laniado, and G. Keren Accelerated intimal thickening in carotid arteries of balloon-injured rats after immunization against heat shock protein 70 J. Am. Coll. Cardiol., November 1, 2001; 38(5): 1564 - 1569. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. C. Berk Vascular Smooth Muscle Growth: Autocrine Growth Mechanisms Physiol Rev, July 1, 2001; 81(3): 999 - 1030. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Patterson, G. A. Stouffer, N. Madamanchi, and M. S. Runge New Tricks for Old Dogs : Nonthrombotic Effects of Thrombin in Vessel Wall Biology Circ. Res., May 25, 2001; 88(10): 987 - 997. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. R. Madamanchi, S. Li, C. Patterson, and M. S. Runge Reactive Oxygen Species Regulate Heat-Shock Protein 70 via the JAK/STAT Pathway Arterioscler. Thromb. Vasc. Biol., March 1, 2001; 21(3): 321 - 326. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. E. Bornfeldt Stressing Rac, Ras, and Downstream Heat Shock Protein 70 Circ. Res., June 9, 2000; 86(11): 1101 - 1103. [Full Text] [PDF]
|
|
|
|
|
|
Q. Xu, G. Schett, C. Li, Y. Hu, and G. Wick Mechanical Stress-Induced Heat Shock Protein 70 Expression in Vascular Smooth Muscle Cells Is Regulated by Rac and Ras Small G Proteins but Not Mitogen-Activated Protein Kinases Circ. Res., June 9, 2000; 86(11): 1122 - 1128. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Rocnik, L. H. Chow, and J. G. Pickering Heat Shock Protein 47 Is Expressed in Fibrous Regions of Human Atheroma and Is Regulated by Growth Factors and Oxidized Low-Density Lipoprotein Circulation, March 21, 2000; 101(11): 1229 - 1233. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. G. Neschis, S. D. Safford, P. N. Raghunath, D. J. Langer, M. L. David, A. K. Hanna, J. E. Tomaszewski, K. Kariko, E. S. Barnathan, and M. A. Golden Thermal Preconditioning Before Rat Arterial Balloon Injury : Limitation of Injury and Sustained Reduction of Intimal Thickening Arterioscler. Thromb. Vasc. Biol., January 1, 1998; 18(1): 120 - 126. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Zhou, X. Wu, and H. N. Ginsberg Evidence That a Rapidly Turning Over Protein, Normally Degraded by Proteasomes, Regulates hsp72 Gene Transcription in HepG2 Cells J. Biol. Chem., October 4, 1996; 271(40): 24769 - 24775. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Xu, T. W. Fawcett, R. Udelsman, and N. J. Holbrook Activation of Heat Shock Transcription Factor 1 in Rat Aorta in Response to High Blood Pressure Hypertension, July 1, 1996; 28(1): 53 - 57. [Abstract] [Full Text]
|
|