Published online before print August 15, 2002, doi: 10.1161/01.ATV.0000034021.92658.4C
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© 2002 American Heart Association, Inc.
Atherosclerosis |
Differential Accumulation of Proteoglycans and Hyaluronan in Culprit Lesions
Insights Into Plaque Erosion
From the Department of Cardiovascular Pathology, Armed Forces Institute of Pathology, Washington, DC, and the Department of Vascular Biology, The Hope Heart Institute (T.N.W.), Seattle, Wash.
Reprint requests to Renu Virmani, MD, Chairperson, Department of Cardiovascular Pathology, Armed Forces Institute of Pathology, Building 54, Room 2005, 6825 16th St, Washington, DC 20306-6000. E-mail virmani{at}afip.osd.mil
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.
Key Words: culprit plaques • proteoglycans • hyaluronan • CD44 • smooth muscle cells
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