Vessel Wall and Mechanical Properties of Conduit Arteries

The vascular wall is composed of vascular smooth muscle (VSM) cells and extracellular matrix (ECM), which both contribute to the mechanical properties (i.e., arterial stiffness) of large vessels. The elastic behavior depends primarily on the composition and arrangement of the materials that make up the tunica media or middle layer of the vascular wall. In the media of the thoracic aorta and its immediate branches are large attachments of elastic lamellae to VSM cells, constituting the contractile-elastic units, which are arranged in an alternating oblique pattern that exerts maximum forces in a circumferential direction [4]. This arrangement is important for the balance of normal changes in intraluminal pressure and tension that occur during systole and diastole. In a normal young healthy person, the medial fibrous elements of the thoracic aorta contain a predominance of elastin over collagen, but as one proceeds distally along the arterial tree, there is a rapid reversal of the proportion with more collagen than elastin in the peripheral muscular arteries [2-4]. Thus, the thoracic aorta and its immediate branches show greater elasticity, whereas more distal vessels become progressively stiffer.

Close study of the infrastructure of the arterial media has shown that the structure is a composite of subunits, each comprising a group of fascicles of commonly oriented VSM cells surrounded by a similarly oriented array of interconnected elastic fibers [ 4]. The smooth cells of individual fascicles are bound together by a continuous intercellular and pericellular basal lamina (type IV collagen) and by a basketwork of fine collagen fibrils (type III), many of which are embedded in the basal lamina. Separately organized, coarser collagen fibers (type I) appear as bundles between adjacent musculo-elastic fascicles and only occasionally within them. The size, orientation and distribution of the musculo-elastic fascicles in relation to curves and branch regions suggest that they are aligned along lines of tensile force. The fiber bundles are crimped so that configurational rigidity may also contribute resistance to deformation or stretch. VSM cells are attached to the immediately surrounding elastin bars by a series of firm linear junctions. The collagen bundles are not attached to elastic fibers and are only occasionally attached to cells. This composite of stacked musculo-elastic fascicles results in a specific transmural distribution of aortic medial elements, not in layers of elastin-cells-elastin, but in layers of elas-tin-cells-elastin:collagen:elastin-cells-elastin:collagen, and so on [4].

The protein product of the elastin gene is synthesized by VSM cells and secreted as a monomer, tropoelastin [2-4]. After post-translational modification, tropoelastin is cross-linked and organized into elastin polymers that form concentric rings of elastic fenestrated lamellae around the arterial lumen. Elastin-deficient mice die from an occlusive fibrocellular pathology caused by subendothelial proliferation and accumulation of VSM cells in early neonatal life [5]. Thus, elastin is a crucial signaling molecule that directly controls VSM cell biology, and stabilizes arterial structure and resting vessel diameter. On the other hand, vascular collagen is determined at a very early developmental stage and thereafter remains quite stable, due to a very low turnover. Nevertheless, the proportion of collagen types I and III has a differential mechanical impact on stiffness of the vessel wall [6]. Furthermore, neurohumoral factors, particularly those related to angiotensin II and aldosterone, modulate collagen accumulation [1-3, 6, 7]. Finally, under the influence of several enzymes such as metalloproteinases, collagen is also subjected to important chemical modifications, such as breakdown, cross-linking or glycation, resulting in marked changes in stiffness along the vessel wall [3]. Several other molecules, such as connexins or desmins, may contribute to the three-dimensional distribution of mechanical forces within the arterial wall, acting on cell-cell and cell-matrix attachments and favoring resulting changes in arterial stiffness [8, 9]. Finally, ECM is mostly responsible for the passive mechanical properties of the arteries, in particular of the aorta and its main branches [1, 2]. These passive properties, which must to be studied in the absence of VSM tone (after poisoning VSM cells by potassium cyanide), are usually mathematically defined from a cylindrical model of the artery. When the transmural pressure rises, a curvilinear (and not a linear) pressure-diameter curve ensues, as a consequence of recruitment of elastin at low pressure and of collagen fibers at high pressure (fig. 7) [1, 2]. From this framework, various indices have been described to define arterial stiffness and are summarized in table 1.

Independently of ECM, VSM cells do not represent a homogenous population. For the same genomic background, they have different mixtures of phe-notypes, involving not only contractile and secretory but also proliferative and

Table 1. Arterial stiffness indices [1-3, 12-14] (see also pp. 22-24)

Pulse wave velocity1

Speed of travel of the pulse along an arterial

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