Changes related to age and cerebrovascular symptoms in the extracellular matrix of human carotid plaques.
OBJECTIVE
Many processes involved in the pathogenesis of atherosclerosis result in modifications of the extracellular matrix. These changes not only determine the mechanical stability of atherosclerotic lesions but can directly or indirectly influence further development of the lesions. The purpose of the present study was to compare the matrix composition of human carotid plaques from symptomatic patients with those obtained from patients without symptoms. Furthermore, matrix changes related to age were studied.


METHODS
Thirty atherosclerotic carotid plaques were removed by endarterectomy from 27 patients and divided into 2 groups on the basis of the presence of ipsilateral symptoms. The plaques were homogenized, and the total levels of the major components of the extracellular matrix were determined.


RESULTS
Plaques associated with symptoms were characterized by increased levels of elastin (1.58+/-0.46 versus 1.24+/-0.40 mg/g wet wt; P=0.03) and decreased levels of hydroxyapatite (45.1+/-46.3 versus 131.4+/-111.7 mg/g wet wt; P=0.02) compared with asymptomatic plaques. The increase in elastin in plaques from symptomatic patients was due to elevated levels of an intermediate-size fraction, as determined by liquid chromatography. Collagen and sulfated glycosaminoglycans were present in equal amounts in both groups. Elastin content in carotid plaques decreased with age.


CONCLUSIONS
Carotid plaques from symptomatic patients have lower levels of hydroxyapatite than those from asymptomatic patients. The present study also raises the possibility that non-cross-linked forms of elastin, increased in plaques associated with symptoms, could be a marker of plaque vulnerability and/or directly induce harmful cellular activities or increase lipoprotein retention in the vascular wall.
Gonçalves
Isabel
I
Department of Medicine, Lund University, Wallenberg Laboratory, University Hospital MAS, S-20502 Malmö, Sweden. isabel.goncalves@medforsk.mas.lu.se
Moses
Jonatan
J
Dias
Nuno
N
Pedro
Luís M
LM
Fernandes e Fernandes
José
J
Nilsson
Jan
J
Ares
Mikko P S
MP
D000367:Age Factors; D000368:Aged; D000375:Aging / Q000378:metabolism*; D015415:Biomarkers; D002340:Carotid Artery Diseases / Q000150:complications / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D002561:Cerebrovascular Disorders / Q000209:etiology*; D003094:Collagen / Q000032:analysis / Q000378:metabolism; D017886:Durapatite / Q000032:analysis / Q000378:metabolism; D004549:Elastin / Q000032:analysis / Q000378:metabolism*; D016894:Endarterectomy, Carotid; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006025:Glycosaminoglycans / Q000032:analysis / Q000378:metabolism; D006801:Humans; D008297:Male; D012307:Risk Factors
D015415:Biomarkers; D006025:Glycosaminoglycans; C013786:A73025; D003094:Collagen; D004549:Elastin; D017886:Durapatite