Mechanisms of remodelling: a question of life (stem cell production) and death (myocyte apoptosis).
Remodeling myocytes show a typical switch between the embryonic and classical features of apoptosis and/or hypertrophy representing a signal of death (ie, apoptosis) and a signal of life (ie, hypertrophy). The adult myocyte, however, is a terminal cell; usually it is unable to reproduce and death is not genetically programmed (apoptosis), but occurs by necrosis. The reinstatement of apoptosis and development of hypertrophy during remodeling could be part of the switch forward to the embryonic phenotype with reinstatement of the early embryonic genetic program. Hypertrophy and apoptosis are "sons" of the same "mother": the local, tissue neuroendocrine-neurohumoral response to a mechanical stretch of the myocytes consequent to the geometric changes imposed on the viable myocytes by the necrotic ones. As expected, the life and death cycle is very closely regulated by several autocrine systems, one of which is linked to the interleukin-6 family via a regulatory protein named GP-130. Activation of the GP-130 slows down the death signals, thus favoring hypertrophy and reducing fibrosis.
Ferrari
Roberto
R
University Hospital of Ferrara, Cotignola, Ravenna, Italy. fri@unife.it
Ceconi
Claudio
C
Campo
Gianluca
G
Cangiano
Elisa
E
Cavazza
Caterina
C
Secchiero
Paola
P
Tavazzi
Luigi
L
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D053687:Adult Stem Cells / Q000473:pathology*; D000375:Aging; D000818:Animals; D017209:Apoptosis; D006332:Cardiomegaly / Q000473:pathology; D002395:Catecholamines / Q000502:physiology; D006333:Heart Failure / Q000473:pathology; D006439:Hemodynamics; D006801:Humans; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D009336:Necrosis; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D018487:Ventricular Dysfunction, Left / Q000473:pathology; D020257:Ventricular Remodeling / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D002395:Catecholamines