Changes Related to Age and Cerebrovascular Symptoms in the Extracellular Matrix of Human Carotid Plaques

Abstract

Background and Purpose-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 (1.58Ϯ0.46 versus 1.24Ϯ0.40 mg/g wet wt; Pϭ0.03) and decreased levels of hydroxyapatite (45.1Ϯ46.3 versus 131.4Ϯ111.7 mg/g wet wt; Pϭ0.02) 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.

Soluble Elastin Decreases in the Progress of Atheroma Formation in Human Aorta

“…However, the soluble elastin that we investigated in the present study of aortic specimens showed a decreasing pattern, which is different from the other elastin-associated proteins previously described. 14,[24][25][26][27][28] In the present study, we found that in the non-atherosclerotic aorta soluble elastin was (1) distributed both within the intima and around the mature elastin within the media, (2) different from mature elastic fiber (Figure 1), (3) had the lowest mRNA expression among the 4 histological groups (Figure 3d), (4) present in a low ratio to tropoelastin, which is conjectured to be a marker of elastin synthesis, compared with ruptured plaque (Figure 5), and (5) associated with the activity of MMP-9 among the 4 groups (Figure 3b). These results indicate that in the non-atherosclerotic aorta from subjects approximately 53-84 years of age, soluble elastin is densely distributed and neither endogenous elastogenesis or elastolysis is activated excessively, so soluble elastin may be deposited gradually and preserved within the intima and around the mature elastic fibers within the media over a number of years because the intima is not diseased.…”

Increased aldehyde-modification of collagen type IV in symptomatic plaques – A possible cause of endothelial dysfunction

“…10 Informed consent was given by each patient. The study was approved by the local ethical committee.…”

Low Carotid Calcium Score Is Associated With Higher Levels of Glycosaminoglycans, Tumor Necrosis Factor-Alpha, and Parathyroid Hormone in Human Carotid Plaques

“…Plaques were weighed, homogenized, and elastin, collagen, and sulfated glycosaminoglycans (GAG) were determined as described previously. 3 …”