Normal and abnormal consequences of apoptosis in the human heart. From postnatal morphogenesis to paroxysmal arrhythmias.

Abstract

Apoptosis and necrosis are two distinctly different forms of cell death, and both occur in the human heart. In contrast to necrosis, apoptosis is not associated with inflammation for two reasons. First, the apoptotic cell does not swell or rupture before it is engulfed by either a macrophage or even a neighboring like cell. Second, the phagocytosis occurs with unusual rapidity. Apoptosis, also thought of as cell suicide, is a tidy way of removing cells no longer useful, in essence a form of selective deletion. These features make apoptosis a valuable component of morphogenesis, mediation of hormonal and immunologic responses, and the homeostatic balance between hypertrophy and atrophy or involution. In the human heart apoptosis has been found in the sinus node of patients with the long QT syndrome. It most likely participates in the important postnatal morphogenesis of the sinus node, AV node, and His bundle. Apoptosis may also participate in the genesis and pathophysiology of cardiomyopathy, paroxysmal arrhythmias, or conduction disturbances (some of which may be responsible for sudden death), focal fibromuscular dysplasia of small coronary arteries, hereditary medial degeneration of the tunica media of coronary arteries, and arrhythmogenic right ventricular dysplasia. The possible role apoptosis in numerous other changes in the human heart, among them the pathogenesis of atherosclerosis and mechanisms of aging in the myocardium, merits future investigation.

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

“…This study brings to James' original observations concerning postnatal morphological changes that has been described as present in infants dying in crib death age range who had no morphological abnormalities. 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].…”

“…This term indicates a tidying-up process in which loose strands of surplus conducting tissue are gradually reabsorbed to change AV node and His bundle into their more smooth adult configuration [10,17,41,66]. The resorptive degeneration areas have been described as clusters of young fibroblasts depositing collagen caught in the central fibrous body, sometimes isolated from the ''overdeveloped'' specialized structures, sometimes adjacent to them, without association of inflammation nor massive necrosis or hemorrhage [1,17].…”

“…Similarly, Matturri et al [67] found that the presence of resorptive degeneration resulted not statistically different in age-related subgroups ( P > 0.05). James, in his original work [17], emphasized that the process is ubiquitous at the infancy period, being a normal phenomenon rather than a pathological one, but that ubiquity could not be read as synonymous with safety or stability [10,68]. In fact, it seems that this orderly normal process, if exaggerated, could provoke blocking disruption of the pathway itself, and if defective could leave in place some accessory communications between the AV pathway and the adjacent ordinary myocardium [4,16,23,67].…”

“…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].…”

Beyond early development: Xenopus as an emerging model for the study of regenerative mechanisms

“…Programmed cell death is required to control cell number during morphogenesis and to shape developing organs like the heart and limb as well as craniofacial patterning (James, 1994;Guha et al, 2002;Pajni-Underwood et al, 2007). Recently, Tseng et al (2007) found that apoptosis also plays a crucial role in the early phase of tail regeneration.…”