Artikel
Phospholipase D signal transduction in endomyocardial biopsies from patients with dilated cardiomyopathy
Phospholipase D Signaltransduktion in Endomyokardbiopsien von Patienten mit dilatativer Kardiomyopathie
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Autoren
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C. Burgdorf
- UKSH Campus Lübeck (Lübeck, D)
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A. Prey
- UKSH Campus Lübeck (Lübeck, D)
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H. Schunkert
- UKSH Campus Lübeck (Lübeck, D)
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T. Kurz
- UKSH Campus Lübeck (Lübeck, D)
| Veröffentlicht: | 10. August 2005 |
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Gliederung
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Objective: Phospholipase D (PLD) plays a central role in receptor-regulated signaling pathways associated with the development of cardiomyopathy. PLD catalyses the hydrolysis of phosphatidylcholine (PC) to generate phosphatidic acid (PA), an important regulator of cardiac function. PA is dephosphorylated by PA phosphohydrolase (PAP) to diacylglycerol(DAG)which is responsible for sustained protein kinase C activation in the cell. Although PLD is emerging as a central agent in signal transduction, alterations of PLD in the diseased human heart have not been characterized yet.
Methods: The present study investigated myocardial PLD signal transduction in right ventricular endomyocardial biopsies from 14 patients with decreased left ventricular function due to dilated cardiomyopathy (DCM) and in 9 patients with suspected myocarditis who turned out to have normal left ventricular function at cardiac catheterization, without signs of inflammatory disease in the biopsy (control). Coronary artery disease was excluded by coronary angiography in all cases.
Results: DCM and control were not different regarding age (DCM 46±4, control 44±4 years), body mass index (DCM 29.3±1.9, control 28.4±1.8), and aortic pressure (DCM 95±4, control 101±7 mmHg), but differed significantly in LVEF (DCM 44±5, control 64±5%), pulmonary arterial pressure (DCM 26±3, control 15±2 mmHg), and wedge pressure (DCM 17±2, control 10±2 mmHg). The activity of PC-specific PLD in the biopsies was determined by a HPLC-fluorescence detection method. PLD activity in the DCM group was significantly decreased compared to control (p=0.013; Figure).
Conclusion: The results demonstrate for the first time alterations of PLD signal transduction in the diseased human heart.Whether this decreased PLD activity is accompanied by changes in PAP-catalyzed DAG formation is under current investigation.
Figure 1 [Fig. 1]
