The heart is a singular organ. Its operation as an engine for the
circulatory system has its pillars in a tissue structure specially adapted to
meet the demands of activity during times of rest and exercise. However, none of the processes that occur during cardiac contraction can be fully understood without taking into account the role the extracellular space. This three-dimensional structure serves as a framework for all the cells contained in the myocardium (Image: Decellularised heart tissue), but far from to have the sole scaffolding function, it is involved in a wide range of processes at different levels. First, it can be divided into the solid and the fluid components. By acting as a liaison between the cellular components of the myocardium the extracellular matrix integrates in each excitation the contribution of each individual cell and allows the coordinated contraction of the whole tissue at the macroscopic level. The fluid component allows the distribution of a wide variety of soluble proteins and other molecules related to many cardiac processes and, in addition, various components of the extracellular matrix serve as specific sites for the attachment of many soluble molecules, affecting its availability and distribution. Other components, extremely hydrophilic, play a fundamental role accumulating water, which provides excellent resistance to compression. The organization, composition and density of the extracellular space are dynamic not only in pathological conditions, but also under normal conditions. These three properties are in a constant change in response to different demands, and they all have an impact on the function of the myocardium (Baudino, 2006).
The cardiac extracellular space is composed of a mixture of components of different nature. Proteins, sugars and lipids are normal components of the different extracellular structures. Proteins are particularly prone to associate with other components in order to build hybrid elements such as glycoproteins, proteoglycans or lipoproteins, and they all definitively contribute to the operation and maintenance of the extracellular space as a whole. For this reason, it is difficult to establish an appropriate classification of the protein components of the extracellular space, both at cardiac and general levels. Functional classifications yield heterogeneous groups in phylogenic terms, while organizations based solely on phylogeny are complicated to explain functionally. Additionally, although sequence homologies are large in many cases, post-translational modifications result in significant differences and there are also variations in tissue distribution.
Although there is no appropriate classification for all approaches, we will try to be as fair as possible in order to classify the extracellular components in a comprehensive fashion. Thus, four groups of extracellular proteins will be considered hereinafter:
(4) Non-glycosylated proteins closely related to extracellular matrix.
(5) Soluble components of the extracellular space: proteases, growth factors, cytokines, lipoproteins and hormones.
(6) Cell-matrix interaction components: being not constituent parts of the extracellular space, they are key for the establishment of physical interactions cell-matrix and therefore, central for the homeostasis and normal and pathological remodeling of the extracellular matrix.
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Submitted by: Barallobre-Barreiro J, Spain