The protein composition of the normal and diseased cardiac myocyte

We present a classification of the proteins of the cardiomyocyte based on structural and functional properties of the various components of this cell. The following protein families are categorized: 1) the contractile proteins, responsible for the contractile properties; 2) the sarcomeric skeleton, including titin, α-actinin, myomesin, M-protein, and C-protein, that keeps the contractile filaments in register and ensures sarcomeric stability; 3) the cystoskeletal proteins, i.e., desmin and the microtubules, that maintain the structural order within the cell and connect the cytoplasm and all cellular organelles with the sarcolemma; 4) membrane-associated proteins, such as vinculin, talin, dystrophin, and spectrin, that link the structural components of the intracellular milieu with those of the extracellular matrix via the integrins; and 5) proteins of the intercalated disc, including the cadherins, catenins, desmoplakin, connexin 43, and several others, that ensure stability of the longitudinal cardiomyocyte connections and facilitate impulse conduction. This classification not only is useful from a structural point of view but also is reflected in the functional behavior of these proteins in different pathophysiological situations, e.g., acute ischemia or chronic damage such as heart failure. Structural alterations, as shown here in human myocardium with chronic heart failure, demonstrate graded sensitivity to pathophysiologic stimuli in that the contractile proteins are the most sensitive proteins and the cytoskeleton and the membrane-associated proteins show a compensatory increase and are more resistant against noxious stimuli. From these findings, it is concluded that these reactions to degenerative chronic processes reflect the survival priorities of the cells.