Fischer, Thomas H. and Herting, Jonas and Eiringhaus, Joerg and Pabel, Steffen and Hartmann, Nico H. and Ellenberger, David and Friedrich, Martin and Renner, Andre and Gummert, Jan and Maier, Lars S. and Zabel, Markus and Hasenfuss, Gerd and Sossalla, Samuel (2016) Sex-dependent alterations of Ca2+ cycling in human cardiac hypertrophy and heart failure. EUROPACE, 18 (9). pp. 1440-1448. ISSN 1099-5129, 1532-2092
Full text not available from this repository. (Request a copy)Abstract
Aims Clinical studies have shown differences in the propensity for malignant ventricular arrhythmias between women and men suffering from cardiomyopathies and heart failure (HF). This is clinically relevant as it impacts therapies like prophylactic implantable cardioverter-defibrillator implantation but the pathomechanisms are unknown. As an increased sarcoplasmic reticulum (SR) Ca2+ leak is arrhythmogenic, it could represent a cellular basis for this paradox. Methods/Results We evaluated the SR Ca2+ leak with respect to sex differences in (i) afterload-induced cardiac hypertrophy (Hy) with preserved left ventricular (LV) function and (ii) end-stage HF. Cardiac function did not differ between sexes in both cardiac pathologies. Human cardiomyocytes isolated from female patients with Hy showed a significantly lower Ca2+ spark frequency (CaSpF, confocal microscopy, Fluo3-AM) compared with men (P < 0.05). As Ca2+ spark width and duration were similar in women and men, this difference in CaSpF did not yet translate into a significant difference of the calculated SR Ca2+ leak between both sexes at this stage of disease (P < 0.14). Epifluorescence measurements (Fura2-AM) revealed comparable Ca2+ cycling properties (diastolic Ca2+ levels, amplitude of systolic Ca2+ transients, SR Ca2+ load) in patients of both sexes suffering from Hy. Additionally, the increased diastolic CaSpF in male patients with Hy did not yet translate into an elevated ratio of cells showing arrhythmic events (Ca2+ waves, spontaneous Ca2+ transients) (P < 0.77). In the transition to HF, both sexes showed an increase of the CaSpF (P, 0.05) and the sex dependence was even more pronounced. Female patients had a 69 +/- 10% lower SR Ca2+ leak (P < 0.05), which now even translated into a lower ratio of arrhythmic cells in female HF patients compared with men (P < 0.001). Conclusion These data show that the SR Ca2+ leak is lower in women than in men with comparable cardiac impairment. Since the SR Ca2+ leak triggers delayed afterdepolarizations, our findings may explain why women are less prone to ventricular arrhythmias and confirm the rationale of therapeutic measures reducing the SR Ca2+ leak.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; PROTEIN-KINASE-II; VENTRICULAR MYOCYTES; RYANODINE RECEPTOR; GENDER-DIFFERENCES; RAT; MECHANISMS; DEATH; WOMEN; MICE; Heart failure; Sex/gender; Calcium cycling; SR calcium leak; Arrhythmias |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 03 Apr 2019 13:04 |
| Last Modified: | 03 Apr 2019 13:04 |
| URI: | https://pred.uni-regensburg.de/id/eprint/3348 |
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