[Myocardial hypertrophy after myocardial infarct: what is the significance of phenotype changes in cardiocytes?].
Following myocardial infarction, there are structural changes in the surviving restmyocardium, including excentric hypertrophy. These changes are called "remodelling". It includes hypertrophy of the terminally differentiated cardiocytes and proliferation of other myocardial cells (e.g. connective tissue). In the hypertrophied cardiocytes, the pattern of gene expression is changing towards a perinatal-like phenotype. This phenotype change is called "dedifferentiation" and includes (among others) several critical alterations in myocyte Ca+(+)-homeostasis and electromechanical coupling: prolongation of the action potential and thereby augmented Ca+(+)-inflow into the cardiocyte during activation; reduced expression of sarcoplasmic reticulum Ca+(+)-ATPhase with retarded endsystolic Ca+(+)-reaccumulation into the sarcoplasmic reticulum; enhanced expression of the sarcolemmal Na(+)-Ca+(+)-exchanger with enhanced Ca+(+)-export via this rheogenic, asymmetrical exchanger, this export associated with depolarizing netto-inward current. Due to this phenotype constellation, high heart rates can induce cytosolic Ca+(+)-overload, relaxation abnormalities, depressed systolic force-frequency relations, and diastolic Ca+(+)-induced Ca+(+)-release leading to late afterdepolarizations and triggering ventricular tachyarrhythmias. While the poorly differentiated cardiocytes of newborns have a phenotype similar to that in hypertrophied dedifferentiated cardiocytes of overloaded myocardium (at least in some aspects of Ca+(+)-homeostasis), the neonatal heart is protected against arrhythmias by its high intercellular coupling (high density of "gap-junctions") and by its lower size. In contrast, the intercellular coupling in overloaded myocardium is often heterogeneous, the density of gap junctions is globally reduced, and the conductance of gap-junctions is functionally reduced by cytosolic Ca+(+)-overload. This enhances the susceptibility for arrhythmias due to "reentry" as well as due to focal depolarization of multiple origins.(ABSTRACT TRUNCATED AT 250 WORDS)
Holtz
J
J
Institut für Pathophysiologie der Martin-Luther-Universität, Halle/Wittenberg.
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D002312:Cardiomyopathy, Hypertrophic / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004562:Electrocardiography / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology; D010641:Phenotype
D000806:Angiotensin-Converting Enzyme Inhibitors; D015220:Calcium Channels; D002118:Calcium
Myokardhypertrophie nach Myokardinfarkt: Welche Bedeutung haben die Phänotypveränderungen der Kardiozyten?