Arterial Stiffness and Extracellular Matrix

Javier Díez

Division of Cardiovascular Sciences, Centre for Applied Medical Research and University Clinic, School of Medicine, University of Navarra, Pamplona, Spain


The growing prevalence and associated risk of arterial stiffness provide a major challenge to better understand the underlying causes and the resultant physiological impact of this condition. Structural components within the arterial wall, mainly collagen and elastin, are considered to be major determinants of arterial stiffness. Thus, quantitative and qualitative alterations of collagen and elastin fibers are involved in arterial stiffening that is associated with the aging process and disease states such as hypertension, diabetes, atherosclerosis, and chronic renal failure. Elucidation of mechanisms leading to the above alterations will aid in more specifically targeted therapeutic interventions because currently available cardiovascular medications fall short at reducing the stiffness of the large arteries. Reduction of arterial stiffness will likely have a significant impact on morbidity and mortality of older adults, as well as subjects suffering from cardiovascular and renal diseases.

Copyright © 2007 S. Karger AG, Basel


Increased arterial stiffness is a hallmark of the aging process and the consequence of many disease states such as hypertension, diabetes, atherosclerosis, and chronic renal failure. Accordingly, there is a marked increase in the incidence and prevalence of clinical surrogate markers of arterial stiffness, such as pulse pressure and isolated systolic hypertension, with age and these associated conditions [1-5]. Arterial stiffness is also a marker for increased

Table 1. Collagen types present in vascular tissue classified in accordance with their structural properties





Type I Type III Type V

Type IV Type VIII

Type XV Type XVIII Type XIX

Type VI

cardiovascular risk, including myocardial infarction, heart failure, and total mortality, as well as stroke, dementia, and renal disease [6-14].

Although arterial stiffness is a dynamic parameter, which can be modulated by changes in smooth muscle tone [15], endothelial function [16], and the vasa vasorum microcirculation network [17], it is classically recognized that structural components within the arterial wall, mainly extracellular (ECM) macromolecules, together with transmural pressure are the major determinants of arterial stiffness [18], This chapter reviews the contribution of ECM macromolecules to arterial stiffness, including the roles of collagen, elastin, and other ECM proteins. In addition, the potential role of vascular integrins that act as a link between the ECM and the intracellular environment will also be considered.

Vascular Collagen

By definition, a collagen is a structural protein of the ECM that contains at least one domain in the characteristic triple helical conformation [19], The triple helix is formed by three polypeptide chains (a chains). All collagen molecules are characterized by a central collagen domain composed of repeating Gly-Xaa-Yaa triplets, a high concentration of proline, alanine, and lysine residues and non-collagenous domains at their terminal ends [20, 21]. To date, 20 different collagen types have been identified [22], Collagen types I, III, IV, V, VI, VIII, XV, XVIII, and XIX have all been detected in normal adult vascular tissue [23-27]. Based on their structural properties, these collagens can be described as fibrillar and non-fibrillar (table 1). Fibrillar collagen types I and III are the major collagens detectable in vessels, representing 60 and 30% of vascular collagens, respectively [28, 29], These molecules contain triple helical domains of about 1,000 amino acids, highly conserved carboxy-terminal non-collagenous domains of about 250 amino acids, and variable amino-terminal non-collagenous domains of 50-520 amino acids [20] (fig. 1).

Globular Triple Telo-domain helix peptide

Amino-terminal propeptide

3,000 A

3,000 A

Globular Triple Telo-domain helix peptide

Amino-terminal propeptide

Collagen Triple-helical domain t

0 0

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