Normal and Abnormal Consequences of Apoptosis in the Human Heart

Abstract

Knowledge about apoptosis has become essential for understanding many aspects of cardiac structure and function. In the human heart there are major periods of morphogenesis that begin only after birth, and some of these processes recur intermittently for many years. Although the exact mechanisms by which these events are initiated or terminated remain poorly understood, it is clear that their benefits may be mirrored in destructive effects. In this review, selected examples include normal morphogenesis of the cardiac conduction system and the normal postnatal involution of the right ventricle, both of which are mediated by apoptosis. Destructive counterparts include familial heart block ending in fatal arrhythmias, similar results in the long QT syndrome, and the pathogenesis of both Uhl's anomaly and arrhythmogenic right ventricular dysplasia; in each apoptosis is an important factor.

Crib death: further support for the concept of fatal cardiac electrical instability as the final common pathway

“…This is what James first referred as ''molding and shaping'' of the atrio-ventricular (AV) node and His bundle, a process never claimed as unique to crib death but that, on the contrary, must be considered a normal postnatal morphological change [10,17,18]. This postnatal morphogenesis is mediated by apoptotic death of myocytes in both the sinus node and the AV junctional tissue [39,40]. Since there is no associated inflammation or other indicators of necrosis, some authors have considered such changes as normal or harmless.…”

“…The programmed cell death named apoptosis is of particular interest [98 -102]; its unpredictable occurrence could play a role in the pathogenesis of crib death [10,40,51,98]. Matturri et al [98], in a study on eight crib death and three control hearts, found that the apoptotic indices (AI) in AV node, His bundle, bundle branches, did not to have statistically significant differences ( P>0.05), while in the resorptive degeneration areas the AI resulted higher in control than crib death group.…”

“…While the changes in the AV node and His bundle are principally smoothing of the margins of these two structures and eliminating surplus tissue that can be dangerous if not removed, the changes in the sinus node are quite different, amounting more or less to a total restructuring of the interior of the sinus node itself: the fetus and the infant have sinus nodes composed primarily of P cells whereas the sinus node of the adult human always contains a mixture of transitional cells and P cells. These changes occur either by transformation of some of the P cells to transitional cells or by death of P cells to be replaced by transitional cells, perhaps migrating in from the margins of the sinus node [10,39,40]. Cardiac arrhythmias, such as atrial fibrillation or atrial flutter, as well as distortions in sinus rhythm, including episodes of sinus arrest or tachycardia or ectopic beading, are facilitated by impaired activity of the sinus node during its molding [39,40].…”

“…The most common finding discussed was the postnatal morphogenesis first defined by James as ''resorptive degeneration'' [17], consisting of areas of degeneration, cell death mainly by apoptosis [10,39,40], and replacement fibrosis, beginning about 1 or 2 weeks after birth [10], and being usually completed in the first year of life [17,41]. James' concept has been confirmed by Ferris [20], Marino and Kane [42] and Rossi et al [1,4,22,43], but the validity of his findings has been questioned by other investigators [11,21,33,44].…”

Uhl's anomaly detected in‐utero

“…A possible explanation of Uhl's anomaly is that the right ventricular myocardium undergoes selective apoptosis in utero 9 10 Apoptosis is a type of cell death that is considered a normal phenomenon in postnatal heart maturation 9 . The excessive right ventricular myocardial mass is reduced via apoptosis due to the reduction of the pressure against the right ventricle after birth 11 .…”