Relationship between Na+-Ca2+-exchanger protein levels and diastolic function of failing human myocardium | |
Article | |
关键词: FORCE-FREQUENCY RELATION; CARDIAC SARCOPLASMIC-RETICULUM; HUMAN DILATED CARDIOMYOPATHY; HUMAN HEART-FAILURE; NA-CA EXCHANGE; NA+-CA2+ EXCHANGER; NONFAILING HEARTS; GENE-EXPRESSION; RAT-HEART; MUSCLE; | |
DOI : 10.1161/01.CIR.99.5.641 | |
来源: SCIE |
【 摘 要 】
Background-In the failing human heart, sarcoplasmic reticulum (SR) calcium handling is impaired, and therefore, calcium elimination and diastolic function may depend on the expression of sarcolemmal Na+-Ca2+ exchanger. Methods and Results-Force-frequency relations were studied in ventricular muscle strip preparations from failing human hearts (n=29). Protein levels of Na+-Ca2+ exchanger and SR Ca2+-ATPase were measured in the same hearts. Hearts were divided into 3 groups by discriminant analysis according to the behavior of diastolic function when stimulation rate of muscle strips was increased from 30 to 180 min(-1). At 180 compared with 30 min(-1), diastolic force was increased by 160%, maximum rate of force decline was decreased by 46%, and relaxation time was unchanged in group III. In contrast, in group I, diastolic force and maximum rate of force decline did not change, and relaxation time decreased by 20%. Na+-Ca2+ exchanger was 66% higher in group I than in group III. Na+-Ca2+ exchanger was inversely correlated with the frequency-dependent rise of diastolic force when stimulation rate was increased (r=-0.74; P<0.001). Compared with nonfailing human hearts (n=6), SR Ca2+-ATPase was decreased and Na+-Ca2+ exchanger unchanged in group III, whereas Na+-Ca2+ exchanger was increased and SR Ca2+-ATPase unchanged in group I. Results with group II hearts were between those of group I and group LU hearts. Conclusions-By discriminating failing human hearts according to their diastolic function, we identified different phenotypes. Disturbed diastolic function occurs in hearts with decreased SR Ca2+-ATPase and unchanged Na+-Ca2+ exchanger, whereas increased expression of the Na+-Ca2+ exchanger is associated with preserved diastolic function.
【 授权许可】
Free