Reduced myocardial sarcoplasmic reticulum Ca(2+)-ATPase mRNA expression and biphasic force-frequency relations in patients with hypertrophic cardiomyopathy
| Autor: | Kohzo Nagata, Mitsuhiro Yokota, Fuji Somura, Akiko Noda, Yasushi Takeichi, Mitsunori Iwase, Takao Nishizawa, Yoshiji Yamada, Hideo Izawa, Ryoji Ishiki |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Adult
medicine.medical_specialty Heart Ventricles Cardiomyopathy Calcium-Transporting ATPases Calsequestrin Gene Expression Regulation Enzymologic Muscle hypertrophy Sarcoplasmic Reticulum Calcium-Transporting ATPases Contractility Ventricular Dysfunction Left Heart Rate Physiology (medical) Internal medicine Tachycardia medicine Humans RNA Messenger Ejection fraction Ryanodine receptor business.industry Reverse Transcriptase Polymerase Chain Reaction Myocardium Hypertrophic cardiomyopathy Cardiac Pacing Artificial Hemodynamics Cardiomyopathy Hypertrophic Middle Aged medicine.disease Phospholamban Endocrinology Calcium Cardiology and Cardiovascular Medicine business |
| Zdroj: | Circulation. 104(6) |
| ISSN: | 1524-4539 |
| Popis: | Background — The relationship between left ventricular (LV) contractile functional reserve and gene expression of Ca 2+ -handling proteins in patients with hypertrophic cardiomyopathy (HCM) remains to be clarified. Methods and Results — We calculated the maximum first derivative of LV pressure (LV dP/dt max ) and the LV pressure half-time (T 1/2 ) during pacing in 14 patients with nonobstructive HCM (LV ejection fraction >55%) and 7 control subjects. Endomyocardial tissue was obtained, and mRNA levels of sarcoplasmic reticulum Ca 2+ -ATPase (SERCA2), ryanodine receptor-2, phospholamban, calsequestrin, and Na + /Ca 2+ exchanger were quantified by use of a real-time quantitative reverse transcription—polymerase chain reaction method. Group A consisted of 7 HCM patients who showed a progressive rise in the LV dP/dt max with increased heart rate. Group B consisted of 7 HCM patients in whom the heart rate—LV dP/dt max relation was biphasic at physiological pacing rates. Both the mean maximal wall thickness and the LV hypertrophy score in group B were greater than in group A (20±5 versus 15±3 mm and 7±1 versus 5±2 points, respectively). SERCA2 mRNA levels were significantly lower in group B (SERCA2/GAPDH ratio 0.34±0.15) compared with group A (0.72±0.27) and control subjects (0.85±0.47), whereas the mRNA expression of ryanodine receptor-2, phospholamban, calsequestrin, and Na + /Ca 2+ exchanger were similar in all groups. Conclusions — These results suggest that downregulation of SERCA2 mRNA, resulting in altered Ca 2+ handling, may contribute to impaired LV contractile reserve in HCM patients with severe hypertrophy, even in the absence of detectable baseline systolic dysfunction. |
| Databáze: | OpenAIRE |
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