Reduced myocardial sarcoplasmic reticulum Ca 2+ -ATPase mRNA expression and biphasic force-frequency relations in patients with hypertrophic cardiomyopathy

Fuji Somura, Hideo Izawa, Mitsunori Iwase, Yasushi Takeichi, Ryoji Ishiki, Takao Nishizawa, Akiko Noda, Kohzo Nagata, Yoshiji Yamada, Mitsuhiro Yokota

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)658-663
Number of pages6
JournalCirculation
Volume104
Issue number6
DOIs
Publication statusPublished - 07-08-2001
Externally publishedYes

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Sarcoplasmic Reticulum Calcium-Transporting ATPases
Hypertrophic Cardiomyopathy
Messenger RNA
Calsequestrin
Sodium-Calcium Exchanger
Ryanodine Receptor Calcium Release Channel
Ventricular Pressure
Heart Rate
Left Ventricular Hypertrophy
Stroke Volume
Hypertrophy
Reverse Transcription
Down-Regulation
Gene Expression
Polymerase Chain Reaction
Proteins

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Somura, Fuji ; Izawa, Hideo ; Iwase, Mitsunori ; Takeichi, Yasushi ; Ishiki, Ryoji ; Nishizawa, Takao ; Noda, Akiko ; Nagata, Kohzo ; Yamada, Yoshiji ; Yokota, Mitsuhiro. / Reduced myocardial sarcoplasmic reticulum Ca 2+ -ATPase mRNA expression and biphasic force-frequency relations in patients with hypertrophic cardiomyopathy In: Circulation. 2001 ; Vol. 104, No. 6. pp. 658-663.
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abstract = "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.",
author = "Fuji Somura and Hideo Izawa and Mitsunori Iwase and Yasushi Takeichi and Ryoji Ishiki and Takao Nishizawa and Akiko Noda and Kohzo Nagata and Yoshiji Yamada and Mitsuhiro Yokota",
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Reduced myocardial sarcoplasmic reticulum Ca 2+ -ATPase mRNA expression and biphasic force-frequency relations in patients with hypertrophic cardiomyopathy . / Somura, Fuji; Izawa, Hideo; Iwase, Mitsunori; Takeichi, Yasushi; Ishiki, Ryoji; Nishizawa, Takao; Noda, Akiko; Nagata, Kohzo; Yamada, Yoshiji; Yokota, Mitsuhiro.

In: Circulation, Vol. 104, No. 6, 07.08.2001, p. 658-663.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Reduced myocardial sarcoplasmic reticulum Ca 2+ -ATPase mRNA expression and biphasic force-frequency relations in patients with hypertrophic cardiomyopathy

AU - Somura, Fuji

AU - Izawa, Hideo

AU - Iwase, Mitsunori

AU - Takeichi, Yasushi

AU - Ishiki, Ryoji

AU - Nishizawa, Takao

AU - Noda, Akiko

AU - Nagata, Kohzo

AU - Yamada, Yoshiji

AU - Yokota, Mitsuhiro

PY - 2001/8/7

Y1 - 2001/8/7

N2 - 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.

AB - 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.

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U2 - 10.1161/hc3101.093869

DO - 10.1161/hc3101.093869

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