Load-dependent induction of apoptosis in multicellular myocardial preparations.

TY - JOUR

T1 - Load-dependent induction of apoptosis in multicellular myocardial preparations.

AU - Janssen, P M L

AU - Hasenfuss, G

AU - Zeitz, Oliver

AU - Lehnart, S E

AU - Prestle, J

AU - Darmer, D

AU - Holtz, J

AU - Schumann, H

PY - 2002

Y1 - 2002

N2 - Increased mechanical load has been proposed as an inductor of apoptosis, but it is unknown whether this can occur in the range of pre- and afterloads that prevail in the beating heart. We investigated apoptosis in cultured rabbit multicellular myocardial preparations over several days. Muscles contracted in absence of pre- and afterload (unloaded isotonic), in absence of preload but in presence of afterload (unloaded isometric), or in presence of both (loaded isometric). After up to 48 h of continuous contractions, apoptosis was assessed by TdT-mediated nick-end labeling (TUNEL) assay and DNA ladder analysis. In muscles that contracted loaded isometric, apoptosis was detected after 6-24 h. After 48 h, apoptosis was most prominent in this group, reflected by a high level of DNA ladder intensity (DLI; 27.8 +/- 11.5), whereas Bcl-xL (on RNA level) was significantly downregulated, and Fas remained unchanged. In unloaded isometric preparations, apoptosis was significantly less (6.9 +/- 5.9 DLI) and very similar to those contracting unloaded isotonic (6.1 +/- 5.1 DLI). We conclude that load-dependent apoptosis can occur at sarcomere lengths achievable in vivo and may mainly result from increased preload.

AB - Increased mechanical load has been proposed as an inductor of apoptosis, but it is unknown whether this can occur in the range of pre- and afterloads that prevail in the beating heart. We investigated apoptosis in cultured rabbit multicellular myocardial preparations over several days. Muscles contracted in absence of pre- and afterload (unloaded isotonic), in absence of preload but in presence of afterload (unloaded isometric), or in presence of both (loaded isometric). After up to 48 h of continuous contractions, apoptosis was assessed by TdT-mediated nick-end labeling (TUNEL) assay and DNA ladder analysis. In muscles that contracted loaded isometric, apoptosis was detected after 6-24 h. After 48 h, apoptosis was most prominent in this group, reflected by a high level of DNA ladder intensity (DLI; 27.8 +/- 11.5), whereas Bcl-xL (on RNA level) was significantly downregulated, and Fas remained unchanged. In unloaded isometric preparations, apoptosis was significantly less (6.9 +/- 5.9 DLI) and very similar to those contracting unloaded isotonic (6.1 +/- 5.1 DLI). We conclude that load-dependent apoptosis can occur at sarcomere lengths achievable in vivo and may mainly result from increased preload.

M3 - SCORING: Zeitschriftenaufsatz

VL - 282

SP - 349

EP - 356

JO - AM J PHYSIOL-HEART C

JF - AM J PHYSIOL-HEART C

SN - 0363-6135

IS - 1

M1 - 1

ER -