Collagens in human atherosclerosis. Immunohistochemical analysis using collagen type-specific antibodies.

Abstract

This study represents a systematic analysis of the distribution of collagen types in human atherosclerotic lesions. Formalin-fixed, paraffin-embedded aortic tissues of 40 lesions from 16 different individuals ranging in age from 1 month to 84 years were examined immunohistochemically using antibodies to type I, III, IV, V, and VI collagens. Preembedding immunoelectron microscopy was used to simultaneously localize type V and VI collagens within the lesions. Localization of type HI collagen was very similar to that of type L and type VI collagen appeared together with these two types of collagen in the thickened intlmas of all stages of the lesion. Type V collagen was not detected in either fatty streaks or the mild Intimal thickening of the aortas of children. With advancing age and lesion progression, the immunoreactivity with anti-type V collagen antibody became more intense. Type IV collagen was detected in the basement membrane region of intimal cells. In advanced lesions thick deposits of type IV collagen were found around the elongated smooth muscle cells. Using immunoelectron microscopy, type V collagen was found to be localized to cross-banded collagen fibers, and type VI collagen was found to be localized to beaded filaments present throughout the interstitium of the thickened intima. These findings suggest that collagens preserve the pathophysiological and functional integrity of the vascular wall by providing mechanical support as well as assuring the proper interaction of cells during the formation of atherosclerotic lesions. (Arteriosclerosis and Thrombosis 1992;12:494-502) KEYWORDS • atherosclerosis • collagen • immunohistochemistryA therosclerosis is a disease of large and medium-/ \ sized arteries and is characterized by focal X A . thickening of the inner portion of the artery wall in association with fatty deposits.1 -2 The common underlying events responsible for lesion formation are intimal smooth muscle cell proliferation, formation of new extracellular matrix by these cells, and the possible accumulation of lipid. Collagens are regarded as important in this disease not only because they represent the major extracellular component in the atherosclerotic plaque and thereby contribute to the occlusive nature of the disease but also because they may play an important role in hemostasis and thrombosis through stimulation of blood platelets. 3 In addition, recent studies have indicated that collagens can influence the proliferation and state of differentiation of smooth muscle cells in vitro.4 -6 Thus, it seems likely that collagens could play a vital role in the pathogenesis of this disease.Collagen is now recognized as a family of proteins of at least 13 genetically distinct subtypes, each of which has a unique tissue specificity. -9 Of these 13 collagen types, six (I, III, IV, V, VI, and VIII) are present in blood vessels. 10 All of these collagen types except type VIII collagen are known to be synthesized by smooth From the Department of Pathology, School of Medicine, Kanazawa University, K...

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

“…14,15 In addition, collagen type IV has been shown to be present in the intima of fatty streaks and in advanced lesions. 16 Collagen type IV interaction to endothelial cells is important for maintaining endothelial cell function. 12 Whether collagen type IV directly interacts with LDL and thereby is exposed to reactive aldehydes, or if this exposure is due to an indirect interaction between collagen type IV and other extracellular matrix proteins/proteoglycans binding LDL, remains to be clarified.…”

Non Insulin Dependent Diabetes in Sand Rat (Psammomys obesus) and Production of Collagen in Cultured Aortic Smooth Muscle Cells. Influence of Insulin

“…[12] The newly synthesised collagen that constitutes the major ECM component, [28] marks the aggravation of the cellular alteration due to diabetes and causes fibrosis state. [29,30,31] In fact, the fibrosis of the aortic wall would be due to the presence of collagen, [32] which is dominant in the proliferative intima. [33] Our qualitative and quantitative study on the phenotypic expression of collagen has shown that cultured SMCs of the normal and diabetic Psammomys obesus synthesise more type I than type III collagen, in accord with the results of Layman et al [34] [36] have shown that SMC produced essentially collagen I and III.…”

“…[33] have noted equally an increase of mRNA coding for 01 (I) zl (III) chains after 30 days of experimental angioplasty. Katsuda et al [32] have shown the coexistence of the two phenotypes in the intimal lesions, but type I collagen would stimulate the SMC migration, t38] During the development of the atherosclerotic process, many authors showed that collagen molecules are also subject to qualitative alterations.…”

Complete Processing of Type III Collagen in Atherosclerotic Plaques

“…22 At least 6 collagen types (I, III, IV, V, VI, and VIII) are present in blood vessels, 23 and a predominance of interstitial collagen types I and III has been documented in atherosclerotic lesions, where they appear to be codistributed in different amounts within all 3 layers of the artery wall. 10,24 Notwithstanding the considerable advances made in the area relating to arterial collagens of normal and atherosclerotic tissues, the available information remains incomplete and, above all, inconsistent and controversial. 20,25,26 The initial work on the status of interstitial collagens 3 suggested that there is a shift in favor of type I collagen in fibrous atherosclerotic lesions compared with the normal arterial wall, where type III collagen predominates.…”

“…The organic matrix of a plaque consists mainly of collagen types I and III, but controversy exists over their contents and changes in their proportions between the healthy and atherosclerotic aorta. [3][4][5][6][7][8][9][10] A currently unknown proportion of type III collagen still carries the amino-terminal propeptide domain of its precursor, type III procollagen. 11 Regarding atherosclerotic manifestations, we have previously demonstrated increased serum levels of this propeptide, PIIINP, after both streptokinase and tissue plasminogen activator treatments after acute myocardial infarction 12,13 and detected increased serum levels of PIIINP in patients with expanding abdominal aortic aneurysms.…”