Table 1.
Biochemical Characteristics of Cardiac PDEs
|
Km(μM) |
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|---|---|---|---|---|---|---|
| Family | Gene | Substrate | cAMP | cGMP | Regulators | Species-dependent expression in the heart |
| PDE1 | 1A | cAMP,cGMP | 115 | 5 | +Ca2+/CaM | • equally expressed in human, rat and mouse hearts, and both CMs an CFs • upregulated in mouse, rat and human failing hearts • upregulated in rat CMs by hypertrophic stimuli • upregulated in rat CFs by fibrotic stimuli |
| 1B | cAMP,cGMP | 24 | 2.4 | • not detected in normal human, rat and mouse hearts | ||
| 1C | cAMP,cGMP | 1 | 1 | • expressed highest in human, modest in mouse, very low in rat hearts, and in mouse CMs • increased in failing human and mouse hearts, primarily restricted in CMs |
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| PDE2 | 2A | cAMP,cGMP | 30 | 20 | +CGMP | • detected in human, rat and mouse hearts, and both CMs and CFs, with higher expression in CFs than CMs • upregulated in human and mouse failing hearts |
| PDE3 | 3A | cAMP,cGMP | 0.15 | 0.15 | −cGMP | • expressed in human, rat, dog and mouse hearts and CMs• increase or decrease in diseased hearts, varied by studies |
| 3B | • expressed in mouse hearts and CMs | |||||
| PDE4 | 4A | cAMP | 5 | N/A | +PKA, −ERK | • expressed in human, rat and mouse hearts and CMs • decreased expression in human failing hearts and rat hypertrophic CMs |
| 4B | • expressed in human, rat and mouse hearts and CMs • decreased expression in human failing hearts and rat hypertrophic CMs |
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| 4C | • not detected in normal rat heart | |||||
| 4D | • expressed in human, rat and mouse hearts and CMs • decreased expression in human and rat failing hearts and rat hypertrophic CMs |
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| PDE5 | 5A | cGMP | N/A | 5 | +PKG | • expressed in human, rat and mouse hearts, and both CMs and CFs • upregulated in human, rat and mouse failing hearts, and diseased CMs |
| PDE8 | 8A | cAMP | 0.05 | N/A | • expressed in human and mouse hearts, and mouse CMs | |
| 8B | • expressed in human and mouse hearts, and mouse CMs | |||||
| PDE9 | 9A | cGMP | 0.1 | • expressed in human and mouse hearts, and CMs • upregulated in human and mouse failing hearts |
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| PDE10 | 10A | cAMP,cGMP | 0.3 | 13 | +CAMP | • expressed in human and mouse hearts, and both CMs and CFs • upregulated in human and mouse failing hearts • upregulated in mouse CMs by hypertrophic stimuli • upregulated in mouse CFs by fibrotic stimuli |