Regulation of cardiomyocyte mechanotransduction by the cardiac cycle

Article

关键词: ACTIVATED PROTEIN-KINASE;    SMOOTH-MUSCLE CELLS;    MECHANICAL-STRESS;    GENE-EXPRESSION;    IN-VITRO;    MYOCYTES;    HYPERTROPHY;    RAT;    STIMULATION;    RELEASE;   

DOI  :  10.1161/01.CIR.103.10.1459

来源: SCIE

【 摘 要 】

Background-Overloading the left ventricle in systole (pressure overload) is associated with a distinct morphological response compared with overload in diastole (volume overload). Methods and Results-We designed a novel computer-controlled experimental system that interfaces biaxially uniform strain with electrical pacing, so that cellular deformation can be imposed during a specified phase of the cardiac cycle. Cardiomyocytes were exposed to strain (4%) during either the first third (systolic phase) or last third (diastolic phase) of the cardiac cycle. Strain imposed during the systolic phase selectively activated p44/42 mitogen-activated protein kinase (MAPK) and MAPK/extracellular signal-regulated protein kinase kinase (MEK1/2, an activator of p44/42 MAPK) compared with strain imposed during the diastolic phase. In contrast, there was no difference in activation of p38 and c-Jun NH2-terminal kinases induced by strain imposed during the systolic phase (5.5- and 3.1-fold versus control, n=4) compared with the diastolic phase (5.5- and 3.1-fold). Induction of both brain natriuretic peptide (5.8-fold versus control, P<0.05, n=3) and tenascin-C (7.0-fold, P<0.02) mRNA expression by strain imposed during the systolic phase was greater than during the diastolic phase (3.9- and 3.6-fold, respectively). [H-3]leucine incorporation induced by strain imposed during the systolic phase (4.0-fold versus control) was greater than during the diastolic phase (2.7-fold, P<0.02, n=4); a selective inhibitor of MEK1/2 inhibited this difference. Conclusions-Mechanical activation of p44/42 MAPK and MEK1/2, gene expression, and protein synthesis is regulated by the cardiac cycle, suggesting that mechanotransduction at the cellular level may underlie differences between pressure and volume overload of the heart.

【 授权许可】

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