Reduced Myocardial Sarcoplasmic Reticulum Ca2+-ATPase Protein Expression in Compensated Primary and Secondary Human Cardiac Hypertrophy

Schotten, Ulrich; Koenigs, Bernd; Rueppel, Marc; Schoendube, Friedrich A.; Boknı́k, Peter; Schmitz, Wilhelm; Hanrath, Peter

doi:10.1006/jmcc.1999.0981

Cited by 22 publications

(12 citation statements)

References 53 publications

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“…Also, isotransient is due to a dysfunction of the sarcoplasmic prenaline-activated, and maximal catalytic capacity of the reticulum probably caused by changes in the expression of AC was unaltered in AF patients. These data provide direct 21 Ca handling proteins [18,23,24]. Also, an upregulation evidence that the b-adrenergic signal transduction pathway…”

Section: Discussionmentioning

confidence: 94%

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Atrial fibrillation-induced atrial contractile dysfunction: a tachycardiomyopathy of a different sort

Schotten

2002

Cardiovascular Research

150

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Objective: Although AF-induced atrial contractile dysfunction has significant clinical implications the underlying intracellular mechanisms are poorly understood. Methods: From the right atrial appendages of 59 consecutive patients undergoing mitral valve surgery (31 in SR, 28 in chronic AF) thin muscle preparations (diameter,0.7 mm) were isolated. Isometric force of contraction was measured in 21 the presence of different concentrations of Ca and isoprenaline. To assess the function of the sarcoplasmic reticulum, the force-frequency relationship and the post-rest potentiation were studied. The myocardial density of the ryanodine-sensitive calcium SR patients contractile force was 10.961.8 mN / mm compared to 3.360.9 mN / mm (n548, P,0.01) in AF patients. The positive inotropic effect of isoprenaline was diminished but the stimulatory effect on relaxation and the adenylyl cyclase were not altered in AF patients. The force-frequency relation and the post-rest potentiation were enhanced in atrial myocardium of AF patients. The protein 1 21 levels of CRC, SERCA, Plb, and Cals were not different between the two groups. In contrast, the Na / Ca -exchanger was upregulated by 67% in atria of AF patients. Conclusions: AF-induced atrial contractile dysfunction is not due to b-adrenergic desensitization or dysfunction of the sarcoplasmic reticulum and thus is based on different cellular mechanisms than a ventricular tachycardia-induced 21 21 cardiomyopathy. Instead, downregulation or altered function of the L-type Ca -channel and an increased Ca extrusion via the 1 21Na / Ca -exchanger seem to be responsible for the depressed contractility in remodeled atria.

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Section: Discussionmentioning

confidence: 94%

“…Results homogenate aliquots was carried out using polyacrylamide 21 gels [18]. After tank blotting the nitrocellulose (0.45 mm) 3.1.…”

Section: Adenylyl Cyclase Activity 21 Patientsmentioning

confidence: 99%

Atrial fibrillation-induced atrial contractile dysfunction: a tachycardiomyopathy of a different sort

Schotten

2002

Cardiovascular Research

150

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“…21,22 In addition, several studies of myocardial samples from HCM patients after myectomy have suggested that functional abnormalities in Ca 2ϩ -handling proteins, including SERCA2, might be involved in abnormal intracellular Ca 2ϩ handling and thus, in impaired contractile performance in HCM patients. [23][24][25] SERCA2 is clearly recognized as a major determinant of myocardial contractility. 26 In a recent study in genetically engineered mice models, Kadambi et al 22 implicated the ratio of SERCA2 to phospholamban as a contributing factor in determining the frequency response of cardiac muscle.…”

Section: Discussionmentioning

confidence: 99%

Reduced Myocardial Sarcoplasmic Reticulum Ca ²⁺ -ATPase mRNA Expression and Biphasic Force-Frequency Relations in Patients With Hypertrophic Cardiomyopathy

et al. 2001

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Background-The relationship between left ventricular (LV) contractile functional reserve and gene expression ofCa 2ϩ -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 Ͼ55%) and 7 control subjects. Endomyocardial tissue was obtained, and mRNA levels of sarcoplasmic reticulum Ca 2ϩ -ATPase (SERCA2), ryanodine receptor-2, phospholamban, calsequestrin, and Na ϩ /Ca 2ϩ 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 (20Ϯ5 versus 15Ϯ3 mm and 7Ϯ1 versus 5Ϯ2 points, respectively). SERCA2 mRNA levels were significantly lower in group B (SERCA2/GAPDH ratio 0.34Ϯ0.15) compared with group A (0.72Ϯ0.27) and control subjects (0.85Ϯ0.47), whereas the mRNA expression of ryanodine receptor-2, phospholamban, calsequestrin, and Na ϩ /Ca 2ϩ exchanger were similar in all groups. Conclusions-These results suggest that downregulation of SERCA2 mRNA, resulting in altered Ca 2ϩ handling, may contribute to impaired LV contractile reserve in HCM patients with severe hypertrophy, even in the absence of detectable baseline systolic dysfunction. (Circulation. 2001;104:658-663.)

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“…The present study mainly concerned p16-PLB, since it is considered to be the major regulator of PLB activity during ␤-adrenergic stimulation (10). Under pathological conditions, several studies have reported decreased expression of SERCA 2a, the predominant isoform in the heart (43), in failing human myocardium (2,34) and in animal models of pressure overload-induced hypertrophy, especially in SHR (3). This abnormality of SERCA 2a would lead to abnormalities in Ca 2ϩ handling, especially significant alteration of [Ca 2ϩ ] i (4,5), which appears to be involved in hypertrophic cell growth (28).…”

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The onset of left ventricular diastolic dysfunction in SHR rats is not related to hypertrophy or hypertension

Dupont

Maizel

Mentaverri

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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Dupont S, Maizel J, Mentaverri R, Chillon JM, Six I, Giummelly P, Brazier M, Choukroun G, Tribouilloy C, Massy ZA, Slama M. The onset of left ventricular diastolic dysfunction in SHR rats is not related to hypertrophy or hypertension. Am J Physiol Heart Circ Physiol 302: H1524 -H1532, 2012. First published January 27, 2012; doi:10.1152/ajpheart.00955.2010.-Left ventricular (LV) diastolic dysfunction, particularly relaxation abnormalities, are known to be associated with the development of LV hypertrophy (LVH). Preliminary human and animal studies suggested that early LV diastolic dysfunction may be revealed independently of LVH. However, whether LV diastolic dysfunction is compromised before the onset of hypertension and LVH remains unknown. We therefore evaluated LV diastolic function in spontaneously hypertensive rats (SHR) at different ages and tested whether LV diastolic dysfunction is associated with abnormal intracellular calcium homeostasis. LV systolic and diastolic functions were evaluated by invasive and echocardiographic methods in 3-week-old (without hypertension) and 5-week-old (with hypertension) SHR and Wistar-Kyoto control rats. Basal intracytoplasmic calcium and sarcoplasmic reticulum (SR) Ca 2ϩ contents were measured in cardiomyocytes using fura-2 AM. Sarco(endo)plasmic Ca 2ϩ -ATPase isoform 2a (SERCA 2a) and phospholamban (PLB) expressions were quantified by Western blot and quantitative RT-PCR techniques. LV relaxation dysfunction was observed in 3-week-old SHR rats before onset of hypertension and LVH. An increase in basal intracytoplasmic Ca 2ϩ and a decrease in SR Ca 2ϩ release were demonstrated in SHR. Decreased expression of SERCA 2a and Ser16 PLB (p16-PLB) protein levels was also observed in SHR rats, whereas mRNA expression was not decreased. For the first time, we have shown that LV myocardial dysfunction precedes hypertension in 3-week-old SHR rats. This LV myocardial dysfunction was associated with high diastolic [Ca 2ϩ ]i possibly due to decreased SERCA 2a and p16-PLB protein levels. Diastolic dysfunction may be a potential predictive marker of arterial hypertension in genetic hypertension syndromes.diastole; ultrasonic; calcium; spontaneously hypertensive rats LEFT VENTRICULAR (LV) DIASTOLIC dysfunction is responsible for more than one half of all hospitalizations for congestive heart failure or acute pulmonary oedema, which has been shown to be the consequence of multiple clinical factors, mostly hypertension (15). LV diastolic dysfunction, particularly relaxation abnormalities, is usually recognized to be closely associated with the development of left ventricular hypertrophy (LVH) in hypertensive humans and spontaneously hypertensive rats (SHR), a model of human genetic hypertension (35). Nevertheless, in a previous study, we demonstrated LV relaxation impairment in young SHR without LVH (37), subsequently confirmed by Aeschbacher et al (1). Di Bello et al. (13) have also demonstrated early LV diastolic dysfunction before the onset of hypertension and LVH. In view of these da...

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Reduced Myocardial Sarcoplasmic Reticulum Ca2+-ATPase Protein Expression in Compensated Primary and Secondary Human Cardiac Hypertrophy

Cited by 22 publications

References 53 publications

Atrial fibrillation-induced atrial contractile dysfunction: a tachycardiomyopathy of a different sort

Atrial fibrillation-induced atrial contractile dysfunction: a tachycardiomyopathy of a different sort

Reduced Myocardial Sarcoplasmic Reticulum Ca ²⁺ -ATPase mRNA Expression and Biphasic Force-Frequency Relations in Patients With Hypertrophic Cardiomyopathy

The onset of left ventricular diastolic dysfunction in SHR rats is not related to hypertrophy or hypertension

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Reduced Myocardial Sarcoplasmic Reticulum Ca2+-ATPase Protein Expression in Compensated Primary and Secondary Human Cardiac Hypertrophy

Cited by 22 publications

References 53 publications

Atrial fibrillation-induced atrial contractile dysfunction: a tachycardiomyopathy of a different sort

Atrial fibrillation-induced atrial contractile dysfunction: a tachycardiomyopathy of a different sort

Reduced Myocardial Sarcoplasmic Reticulum Ca 2+ -ATPase mRNA Expression and Biphasic Force-Frequency Relations in Patients With Hypertrophic Cardiomyopathy

The onset of left ventricular diastolic dysfunction in SHR rats is not related to hypertrophy or hypertension

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Reduced Myocardial Sarcoplasmic Reticulum Ca ²⁺ -ATPase mRNA Expression and Biphasic Force-Frequency Relations in Patients With Hypertrophic Cardiomyopathy