Differential Accumulation of Proteoglycans and Hyaluronan in Culprit Lesions: Insights Into Plaque Erosion
Abstract
Objective— The importance of the extracellular matrix molecules versican, biglycan, decorin, and hyaluronan in plaque instability has not been recognized. Methods and Results— Coronary lesions with acute thrombi and stable plaques were examined for the accumulation and distribution of specific proteoglycans and hyaluronan at culprit sites. The cell surface receptor for hyaluronan, CD44, and smooth muscle (SM) cell maturation markers were also assessed. Proteoglycans and hyaluronan accumulated in distinct patterns depending on plaque type. The fibrous cap of stable lesions was enriched in versican and biglycan, with considerably less staining for decorin and hyaluronan, whereas picrosirius red revealed a heavy accumulation of collagen type I. In contrast, intense staining for hyaluronan and versican was found in erosions at the plaque/thrombus interface, with weak staining for biglycan and decorin; collagen content was predominantly type III. Rupture sites showed little immunoreactivity for proteoglycans or hyaluronan. CD44 was localized along the plaque/thrombus interface in erosions, whereas in ruptures and stable plaques, it was mostly confined to inflammatory cells. Positive immunostaining for immature SM cells (SM myosin heavy chain SM1 and SMemb) was present in stable and eroded plaques, whereas the presence of SM2 and smoothelin was weak or nonexistent. Conclusions— Specific accumulation of versican, hyaluronan, and CD44 at the sites of plaque erosion implicates an involvement of these molecules in events associated with acute coronary thrombosis.
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In plaque erosion, VSMCs are often abundant, amidst a proteoglycan-rich ECM, enriched in type III collagen, versican and hyaluronan.
“but VSMCs are often abundant, amidst a proteoglycan-rich ECM, enriched in type III collagen, versican and hyaluronan 193 .”
From Vascular smooth muscle cells in atherosclerosis (2019) · cites this paper as [193]
Cites
(1968) · Medical Entomology and Zoology · Cited by 4,924 · see citing works
Virmani, R., Kolodgie, F. D., Burke, A. P., Farb, A., & Schwartz, S. M. (2000) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.20.5.1262 · Cited by 4,084 · see citing works
Self-citationMatrix metalloproteinases in vascular remodeling and atherogenesis: the good, the bad, and the ugly.
Galis, Z. S., & Khatri, J. J. (2002) · PubMed · Cited by 1,787 · see citing works
Coronary Risk Factors and Plaque Morphology in Men with Coronary Disease Who Died Suddenly
BURKE, A. P., Farb, A. A., Malcom, G. T., Liang, Y.-H., Smialek, J. E., & Virmani, R. (1997) · New England Journal of Medicine · doi:10.1056/nejm199705013361802 · Cited by 1,739 · see citing works
Self-citationPROTEOGLYCANS: STRUCTURES AND INTERACTIONS
Kjellén, L., & Lindahl, U. (1991) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.60.070191.002303 · Cited by 1,724 · see citing works
Proteoglycans: Structures And Interactions
Kjellén, L. (1991) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.60.1.443 · Cited by 1,602 · see citing works
Matrix Metalloproteinases in Vascular Remodeling and Atherogenesis
Galis, Z. S., & Khatri, J. J. (2002) · Circulation Research · doi:10.1161/res.90.3.251 · Cited by 1,550 · see citing works
The Response-to-Retention Hypothesis of Early Atherogenesis
Williams, K. J., & Tabas, I. (1995) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.15.5.551 · Cited by 1,413 · see citing works
Coronary Plaque Erosion Without Rupture Into a Lipid Core
Farb, A. A., BURKE, A. P., Tang, A. L., Liang, Y.-H., Mannan, P., Smialek, J. E., & Virmani, R. (1996) · Circulation · doi:10.1161/01.cir.93.7.1354 · Cited by 1,274 · see citing works
Self-citationDavies, M. J., Richardson, P. D., Woolf, N., Katz, D. R., & Mann, J. (1993) · Heart · doi:10.1136/hrt.69.5.377 · Cited by 1,127 · see citing works
Macrophage infiltration in acute coronary syndromes. Implications for plaque rupture.
Moreno, P., Falk, E., Palacios, I. F., Newell, J. B., Fuster, V., & Fallon, J. T. (1994) · Circulation · doi:10.1161/01.cir.90.2.775 · Cited by 1,105 · see citing works
Signaling Properties of Hyaluronan Receptors
Turley, E. A., Noble, P. W., & Bourguignon, L. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.r100038200 · Cited by 1,041 · see citing works
Healed Plaque Ruptures and Sudden Coronary Death
BURKE, A. P., Kolodgie, F. D., Farb, A. A., Weber, D. K., Malcom, G. T., Smialek, J. E., & Virmani, R. (2001) · Circulation · doi:10.1161/01.cir.103.7.934 · Cited by 922 · see citing works
Self-citationHyaluronan-binding Proteins: Tying Up the Giant
Day, A. J., & Prestwich, G. D. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.r100036200 · Cited by 567 · see citing works
Hyaluronan-Cell Interactions in Cancer and Vascular Disease
Toole, B. P., Wight, T. N., & Tammi, M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.r100039200 · Cited by 491 · see citing works
Self-citationSandy, J. D., Westling, J., Kenagy, R. D., Iruela‐Arispe, M. L., Verscharen, C., Rodrı́guez-Manzaneque, J. C., Zimmermann, D. R., Lemire, J. M., Fischer, J. W., Wight, T. N., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m009737200 · Cited by 454 · see citing works
Self-citationGlycosaminoglycans and the regulation of blood coagulation
Bourin, M., & Lindahl, U. (1993) · Biochemical Journal · doi:10.1042/bj2890313 · Cited by 424 · see citing works
Localization of Apoptotic Macrophages at the Site of Plaque Rupture in Sudden Coronary Death
Kolodgie, F. D., Narula, J., BURKE, A. P., Haider, N., Farb, A. A., Hui-Liang, Y., Smialek, J. E., & Virmani, R. (2000) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64641-x · Cited by 363 · see citing works
Self-citationThe role of proteoglycans in cell adhesion, migration and proliferation
Wight, T. N., Kinsella, M. G., & Qwarnström, E. E. (1992) · Current Opinion in Cell Biology · doi:10.1016/0955-0674(92)90102-i · Cited by 361 · see citing works
Self-citationHalpert, I., Sires, U. I., Roby, J. D., Potter‐Perigo, S., Wight, T. N., Shapiro, S. D., Welgus, H. G., Wickline, S. A., & Parks, W. C. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.18.9748 · Cited by 359 · see citing works
Self-citationAikawa, M., Sivam, P. N., Kuro-o, M., et al. (1993) · Circulation Research · doi:10.1161/01.res.73.6.1000 · Cited by 343 · see citing works
Cuff, C. A., Kothapalli, D., Azonobi, I., Chun, S. H., Zhang, Y., Belkin, R., Yeh, C., Secreto, A. J., Assoian, R. K., Rader, D. J., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci200112455 · Cited by 330 · see citing works
Comparison of Apolipoprotein and Proteoglycan Deposits in Human Coronary Atherosclerotic Plaques
O’Brien, K. D., Olin, K. L., Alpers, C. E., Chiu, W. S., Ferguson, M. S., Hudkins, K. L., Wight, T. N., & Chait, A. (1998) · Circulation · doi:10.1161/01.cir.98.6.519 · Cited by 271 · see citing works
Self-citationCamejo, G. (1982) · Advances in lipid research · doi:10.1016/b978-0-12-024919-0.50007-2 · Cited by 231 · see citing works
Evanko, S. P., Raines, E. W., Ross, R., Gold, L. I., & Wight, T. N. (1998) · Europe PMC (PubMed Central) · Cited by 216 · see citing works
Self-citationLokeshwar, V. B., & Selzer, M. G. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m003084200 · Cited by 213 · see citing works
Savani, R. C., Wang, C., Yang, B., Zhang, S., Kinsella, M. G., Wight, T. N., Stern, R., Nance, D. M., & Turley, E. A. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117764 · Cited by 200 · see citing works
Self-citationRießen, R., Isner, J. M., Blessing, E., Loushin, C., Nikol, S., & Wight, T. N. (1994) · PubMed Central · Cited by 192 · see citing works
Self-citationvan der Loop, F. T. L., Gabbiani, G., Kohnen, G., Ramaekers, F. C. S., & van Eys, G. J. J. M. (1997) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.17.4.665 · Cited by 177 · see citing works
Screening of ruptured plaques in patients with coronary artery disease by intravascular ultrasound
Ge, J., Chirillo, F., Schwedtmann, J., et al. (1999) · Heart · doi:10.1136/hrt.81.6.621 · Cited by 167 · see citing works
Hyaluronan stimulates tumor cell migration by modulating the fibrin fiber architecture
Hayen, W., Goebeler, M., Kumar, S., Rießen, R., & Nehls, V. (1999) · Journal of Cell Science · doi:10.1242/jcs.112.13.2241 · Cited by 117 · see citing works
Wound healing: A paradigm for lumen narrowing after arterial reconstruction
Geary, R. L., Nikkari, S. T., Wagner, W. D., Williams, J. K., Adams, M. R., & Dean, R. H. (1998) · Journal of Vascular Surgery · doi:10.1016/s0741-5214(98)70296-4 · Cited by 115 · see citing works
Reduced Thrombus Formation by Hyaluronic Acid Coating of Endovascular Devices
Verheye, S., Markou, C. P., Salame, M. Y., Wan, B., King, S. B., Robinson, K. A., Chronos, N. A. F., & Hanson, S. R. (2000) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.20.4.1168 · Cited by 112 · see citing works
Effect of culture conditions on endothelial cell growth and responsiveness
Relou, I. A. M., Damen, C. A., van der Schaft, D. W. J., Groenewegen, G., & Griffioen, A. W. (1998) · Tissue and Cell · doi:10.1016/s0040-8166(98)80032-3 · Cited by 80 · see citing works
Lin, H., Wilson, J. E., Roberts, C. R., Horley, K. J., Winters, G. L., Mr, C., & Bm, M. (1996) · PubMed · Cited by 75 · see citing works
Weigel, P. H., Frost, S. J., LeBœuf, R. D., et al. (2007) · Novartis Foundation symposium · doi:10.1002/9780470513774.ch15 · Cited by 72 · see citing works
Levesque, H., Girard, N., Maingonnat, C., DELPECH, A., Chauzy, C., Tayot, J. L., Courtois, H., & Delpech, B. (1994) · Atherosclerosis · doi:10.1016/0021-9150(94)90007-8 · Cited by 66 · see citing works
Gutierrez, P. S., O’Brien, K. D., Ferguson, M. S., et al. (1997) · Cardiovascular Pathology · doi:10.1016/s1054-8807(97)00001-x · Cited by 64 · see citing works
CD44 can mediate the adhesion of platelets to hyaluronan
Koshiishi, I., Shizari, M., & Underhill, C. B. (1994) · Blood · doi:10.1182/blood.v84.2.390.390 · Cited by 62 · see citing works
Kenagy, R. D., Fischer, J. W., Davies, M. G., et al. (2002) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/hq0302.105376 · Cited by 60 · see citing works
Nakagawa, S., Hanada, Y., Koiwaya, Y., et al. (1988) · Circulation · doi:10.1161/01.cir.78.6.1335 · Cited by 54 · see citing works
Arterial wall proteoglycans--Biological properties related to pathogenesis of atherosclerosis
Radhakrishnamurthy, B., Srinivasan, S. R., Vijayagopal, P., et al. (1990) · European Heart Journal · doi:10.1093/eurheartj/11.suppl_e.148 · Cited by 54 · see citing works
Clinical assessment.of cardiac output
Conway, J. (1990) · European Heart Journal · doi:10.1093/eurheartj/11.suppl_i.148 · Cited by 22 · see citing works
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Yahagi, K., Kolodgie, F. D., Otsuka, F., Finn, A. V., Davis, H. R., Joner, M., & Virmani, R. (2016) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2015.164 · Cited by 548 · see citing works
Self-citation
- Authors
- Kolodgie, F. D., Burke, A. P., Farb, A., Weber, D. K., Kutys, R., Wight, T. N., & Virmani, R.
- Affiliations
- Hope Heart Institute (US)
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2002-10
- Volume
- 22
- Issue
- 10
- Pages
- 1642-1648
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2119761763
- Cited by
- 286
- References
- 44
- Citations by year
- 2026: 6 · 2025: 15 · 2024: 12 · 2023: 13 · 2022: 10 · 2021: 17 · 2020: 17 · 2019: 14 · 2018: 16 · 2017: 12 · 2016: 8 · 2015: 10 · 2014: 12 · 2013: 13 · 2012: 11
- FWCI
- 3.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01 HL61799-02, R01 HL18645, R01HL061799)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Health Sciences › Medicine › Surgery › Coronary Interventions and Diagnostics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- proteoglycans, hyaluronic acid, versican, biglycan, decorin, CD44, plaque erosion, plaque rupture, acute coronary thrombosis, coronary artery disease, extracellular matrix, type I collagen, type III collagen, fibrous cap
- MeSH terms
- Adult, Cell Differentiation, Coronary Artery Disease, Coronary Thrombosis, Extracellular Matrix, Female, Humans, Hyaluronic Acid, Immunohistochemistry, Male, Middle Aged, Muscle, Smooth, Vascular, Myocardium, Phenotype, Chondroitin Sulfate Proteoglycans, Proteoglycans, Biomarkers, Extracellular Matrix Proteins, Death, Sudden, Cardiac, Hyaluronan Receptors, Lectins, C-Type, Versicans, Decorin, Biglycan
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