**1. Introduction**

Heart valves are thin, complex, layered connective tissues that direct blood flow in one di‐ rection through the heart. There are four valves in the heart, located at the entrance to and exit from the ventricular chambers. The normal function of the heart valves is essential to cardiovascular and cardiopulmonary physiology. The opening and closing of valve leaflets at precise times during the cardiac cycles contributes to the generation of sufficiently high pressure to eject blood from the ventricles, and also prevents blood from flowing backwards into the heart instead of forward towards the systemic circulation and the lungs.

The ability of heart valves to open and close repeatedly, as well as the maintenance of the phenotypes of valvular cells, is made possible by their tissue microstructure, specifically the composition and orientation of extracellular matrix (ECM). The ECM within heart valves is primarily comprised of collagen, elastic fibers, and proteoglycans and glycosaminoglycans, although other ECM components are present as well. Taken together, the ECM performs several roles in heart valves. First, the ECM plays a biomechanical role: it is responsible for the unique mechanical behavior of the valve tissue and thus the overall valve function. Sec‐ ond, the valvular cells are bound to and surrounded by the ECM that is located within the immediate vicinity of the cell; this ECM is specifically known as the pericellular matrix (PCM). The PCM influences cell function by serving as a source of ligands for cell surface receptors, which transfers mechanical strains (experienced by the leaflet tissues) to the cells and initiates intracellular signaling pathways. Third, the various types of ECM have differ‐ ent innate mechanical behaviors, for example with collagen being stiffer than elastic fibers,

© 2013 Wiltz et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

and a growing body of research has demonstrated that the phenotype and function of cells, including valve cells, are influenced by the stiffness of the substrate to which they are ad‐ hered [1]. These two latter functions of the ECM are considered to be mechanobiological as opposed to merely biomechanical since they affect cell behavior. Fourth, ECM has binding sites for growth factors and other soluble molecules found in the extracellular space, and thus the ECM serves as a reservoir for numerous bioactive factors than can affect cell behav‐ ior if they are released (such as when the ECM is degraded) or if a cell migrates close to this ECM reservoir.

Overall, the heart valve field is beginning to appreciate that there are numerous interactions between the ECM, valve cells, and valve mechanics. Given the complicated relationships that are being demonstrated, it is not surprising that alterations to the normal arrangement or composition of ECM, which frequently occur in valve disease, significantly and detrimen‐ tally impact valve function in a rather vicious cycle. For this reason, there has been an in‐ creasing effort to characterize the ECM within normal heart valves not only to elucidate valve biomechanics and mechanobiology, but also to obtain a solid basis for comparison with diseased valves.

**Figure 1.** Schematic drawing of stress-strain relationships for collagen and elastin fibers during valve motion, repro‐

The ventricularis layer, close to the inflow surface, is rich in elastin with a moderate amount of collagen, which extends in diastole and recoils during systole [6]. The recoil of elastin re‐ stores the crimp of collagen fibrils and decreases the surface area of the stretched tissue from the closing phase [5]. The thickness of the three layers varies from the base to the free edge

It is worth noting that elastic fibers were found to span the whole leaflet, and connect or an‐ chor three discrete layers together [6,8]. In addition, elastin provides intrafibrillar connec‐ tions between collagen bundles in the fibrosa layer, whereas it forms a three-dimensional interconnected network in the spongiosa layer [8]. During unloading, the intrafiber elastin, which has high extensibility, helps the collagen fibers return to their wavy and crimped state [6]. These interconnected structures of elastic fibers anchor the discrete layers together, and prevent delamination, which therefore improves the continuity of material behavior of the whole leaflet. Table 1 summarizes the key ECM components in the layers and their ma‐

delamination Ventricularis Elastin Restoration of the wavy and crimped state of collagen fibers

The structures of the leaflets described above provide the following critical functions [6,9– 11]: 1) anisotropic mechanical behavior withstanding circumferential stress and extending radially; 2) bilinear biological stress-strain behavior allowing the leaflet to extend before bearing load in the closed phase; 3) elastic recoil to fully open the valve and restore the layer

**Table 1.** The key ECM components in each layer of the leaflet and their major functions

Conferring flexibility, dampening vibrations from closing, and resisting

Extracellular Matrix Organization, Structure, and Function

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of the cusp [7].

jor functions.

**Location Main Component(s) Major Function(s)** Fibrosa Collagen Stress bearing

Spongiosa Glycosaminoglycans and proteoglycans

This chapter will provide an overview of the ECM within heart valves, focusing on the aort‐ ic valve. After detailing the layered structure of the valve leaflets, each type of ECM compo‐ nent will be described and discussed in relation to its role in valve function and, in some instances, valve dysfunction.
