title: Reduced myocardial sarcoplasmic reticulum Ca(2+)-ATPase mRNA expression and biphasic force-frequency relations in patients with hypertrophic cardiomyopathy.
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.
  
  
  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.
authors.affiliation: Cardiovascular Division, Department of Clinical Pathophysiology, the First Department of Internal Medicine, Nagoya University, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Somura
authors.forename: H
authors.initials: H
authors.lastname: Izawa
authors.forename: M
authors.initials: M
authors.lastname: Iwase
authors.forename: Y
authors.initials: Y
authors.lastname: Takeichi
authors.forename: R
authors.initials: R
authors.lastname: Ishiki
authors.forename: T
authors.initials: T
authors.lastname: Nishizawa
authors.forename: A
authors.initials: A
authors.lastname: Noda
authors.forename: K
authors.initials: K
authors.lastname: Nagata
authors.forename: Y
authors.initials: Y
authors.lastname: Yamada
authors.forename: M
authors.initials: M
authors.lastname: Yokota
mesh_terms: D000328:Adult; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000235:genetics* / Q000378:metabolism; D002304:Cardiac Pacing, Artificial / Q000009:adverse effects; D002312:Cardiomyopathy, Hypertrophic / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D015971:Gene Expression Regulation, Enzymologic; D006339:Heart Rate / Q000502:physiology; D006352:Heart Ventricles / Q000473:pathology / Q000503:physiopathology; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D008875:Middle Aged; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D013610:Tachycardia / Q000209:etiology / Q000503:physiopathology; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology
chemical_list: D012333:RNA, Messenger; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506946:ATP2A2 protein, human; D000252:Calcium-Transporting ATPases; D002118:Calcium