Differential accumulation of proteoglycans and hyaluronan in culprit lesions: insights into plaque erosion.
OBJECTIVE
The importance of the extracellular matrix molecules versican, biglycan, decorin, and hyaluronan in plaque instability has not been recognized.


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.
Kolodgie
Frank D
FD
Department of Cardiovascular Pathology, Armed Forces Institute of Pathology, Washington, DC 20306-6000, USA.
Burke
Allen P
AP
Farb
Andrew
A
Weber
Deena K
DK
Kutys
Robert
R
Wight
Thomas N
TN
Virmani
Renu
R
D000328:Adult; D058578:Biglycan; D015415:Biomarkers / Q000032:analysis; D002454:Cell Differentiation / Q000235:genetics; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D003324:Coronary Artery Disease / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D003328:Coronary Thrombosis / Q000209:etiology; D016757:Death, Sudden, Cardiac / Q000473:pathology; D058575:Decorin; D005109:Extracellular Matrix / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D016326:Extracellular Matrix Proteins; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000378:metabolism*; D007150:Immunohistochemistry; D037181:Lectins, C-Type; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D011509:Proteoglycans / Q000378:metabolism*; D053675:Versicans
C546884:BGN protein, human; D058578:Biglycan; D015415:Biomarkers; D011508:Chondroitin Sulfate Proteoglycans; C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; D037181:Lectins, C-Type; D011509:Proteoglycans; C508322:VCAN protein, human; D053675:Versicans; D006820:Hyaluronic Acid