Unravelling the mysteries of collagen and cicatrix after myocardial infarction.

In fictional murder mysteries the person responsible for the crime is often the one least likely to be involved. In contrast, in real life, the culprit is usually the most obvious candidate right from the start. In this particular case, the myocardial collagen matrix is the suspect (and as I shall illustrate, a likely culprit) responsible for at least some of the complications that occur after myocardial infarction. Collagen is at the same time the most obvious suspect and yet one that has been frequently overlooked. There are two reasons for this oversight: first, muscle is the major component of the heart and collagen makes up a small percentage of heart mass. Second, relatively specialised techniques are required to reveal the presence and organisation of the myocardial collagen matrix. For example, the most frequently used histological stain, haematoxylin and eosin, is poor in terms of differentiating collagen and therefore gives the false impression that there is hardly any collagen in the heart. Furthermore, a stain commonly used to detect collagen, trichrome, is in fact not specific for collagen and its use can lead to a substantial underestimation of collagen content [ 11. Only with preparations such as scanning electron microscopy, examination of silver impregnated sections using light microscopy, and the examination of picrosirius red stained sections with polarised light can the presence and organisation of the collagen matrix be appreciated. Why is collagen the obvious suspect? One reason becomes evident when the collagen matrix is visualised. Its organisation, for example connecting neighbouring myocytes, is consistent with a role in maintaining structural integrity. In addition, the strength and stiffness of type I collagen are comparable to steel and are several orders of magnitude greater than muscle. Thus the amount, organisation, and type of collagen are important factors in determining the mechanical properties of the heart. While recent reviews have dealt with the general role that collagen plays in myocardial structure and function [2,3], my objective is to focus on the fate of collagen during and after myocardial ischaemia and in cicatrix formation after infarction, with an emphasis on recently published work.