Elsevier

Atherosclerosis

Volume 166, Issue 1, January 2003, Pages 1-11
Atherosclerosis

Review
Vascular collagens: spotlight on the role of type VIII collagen in atherogenesis

https://doi.org/10.1016/S0021-9150(01)00766-3Get rights and content

Abstract

Collagens play a central role in maintaining the integrity and stability of the undiseased as well as of the atherosclerotic vessel wall. An imbalanced metabolism may lead to uncontrolled collagen accumulation reducing vessel wall velocity, frequently resulting in arterial occlusion or thrombosis. A reduced production of collagen and its uncontrolled degradation may affect the stability of the vessel wall and especially of the atherosclerotic plaques by making them prone to rupture and aneurysm. This review presents an overview on the four groups of vascular collagens and on their role in atherogenesis. The major focus was to highlight the extraordinary role and importance of the short chain network forming type VIII collagen in the extracellular matrix of undiseased arteries and of atherosclerotic plaques. The molecular structure of type VIII collagen, its cellular origin, its implication in atherogenesis, its temporal and spatial expression patterns in human and experimental models of atherogenesis, the factors modulating its expression, and—not at least—its potential function is discussed.

Introduction

Collagen is the major component of the extracellular matrix of the vessel wall and has a critical impact in atherogenesis. Collagen is crucial for the maintenance of vessel wall integrity and elasticity. Tensile strength and elastic resilience of the vessel wall, or tissues in general, depend on the composition of the collagen fibers and their size or diameter [1]. Collagen is involved in the processes of cell differentiation, adhesion, migration, proliferation and apoptosis [2], [3], [4]. In atherogenesis accumulation of collagen which might finally lead to vessel wall occlusion is also essential for the maintenance of plaque stability [5], [6], [7], [8], [9]. It has been reported that the bulk of vascular collagen is produced by smooth muscle cells. However, collagens can also be produced by endothelial cells, adventitial fibroblasts and macrophages [10], [11], [12].

At least 19 different collagens encoded by 33 genes have been described [13], [14]. To form a collagen molecule three procollagen chains assemble to a triple-helical structure which is typical for all collagen molecules. Collagen biosynthesis includes a variety of transcriptional and posttranslational, intracellular and extracellular events. Intracellular processes include regulation of transcription and mRNA stability, formation of the α procollagen chains, hydroxylation, glycosylation, assembly of the procollagen chains, and secretion. Extracellular processes include processing of the procollagen molecules, assembly of the collagen fibrils and cross-linking [13], [15].

Section snippets

Vascular collagens

Among the 19 collagens described 13 collagens are found in the vessel wall or are expressed by cells of the vessel wall in vitro (for summary Table 1, Table 2). However, none of these collagens is restricted to the vessel wall. According to the macromolecular structure which is constituted by the various collagen molecules, the vascular collagens are subdivided into three morphologically distinct groups: fibrilar collagens, non-fibrilar collagens (fibril associated collagens; microfibrilar

Fibrilar collagens

Among the vessel wall collagens, fibrilar collagen dominates. In the atherosclerotic plaque it comprises up to 60% of total protein [16]. The collagen fibers being responsible for tensile strength and elastic resilience are mainly composed of type I and type III collagen [17], [18], [19]. To a minor degree collagen fibrils also contain type V collagen [20], [21], [22]. In contrast to the large, parallelly running, densely packed collagen fibrils of tendon or bone, vascular collagen fibrils are

Non-fibrilar collagens

In comparison with fibrilar collagens, the members of the other collagen groups (for summary see Table 1) are less abundant in the vessel wall. Nevertheless, their lower abundance must not necessarily be related with lower functional impact.

Fibril associated collagens, so-called FACIT collagens [47], like type XIV and type XVI collagen, consist of a shorter and a longer triple-helical domain connected by a short non-helical region. The longer one of the two triple-helices binds specifically to

Network forming type VIII collagen

During the last years network forming type VIII collagen became an increasing focus of interest, particularly in the context of atherogenesis.

Expression of type VIII collagen by cells of the vessel wall in vitro and occurrence in normal and atherosclerotic arteries

In the vessel wall, type VIII collagen is widely distributed. Its expression by endothelial cells, smooth muscle cells and monocytes/macrophages (cellular functions are summarized in Table 3), points to a fundamental role in vessel physiology.

Concluding remarks

While the particular function of type VIII collagen in the vasculature is elusive yet, the data summarized in this review suggest a role of type VIII collagen in the maintenance of vessel wall integrity and structure. The interactions of type VIII collagen with other components of the vascular extracellular matrix is summarized in Fig. 1. Analogous to its role in the Descemet's membrane of the cornea, type VIII collagen might constitute a 3-D meshwork stabilizing the vascular wall. It might

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