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Phosphorylation of G Protein–Coupled Receptors: GPCR Kinases in Heart Disease
Table 1.
Animal Models of Cardiac Dysfunction and Therapeutic Modulation of GRK Activity
| Cause of dysfunction | Symptoms | Therapeutic agent | Therapeutic consequence | Reference |
|---|---|---|---|---|
| a ↓ indicates qualitative or quantitative loss of given characteristic; ↑ indicates qualitative or quantitative increase. | ||||
| b Mutational ablation of muscle LIM protein. | ||||
| c Dilated cardiomyopathy. | ||||
| d Calsequestrin. | ||||
| e Myosin heavy chain. | ||||
| f Hypertrophic cardiomyopathy. | ||||
| g Left ventricular. | ||||
| h Sympathetic nervous system. | ||||
| i Right ventricular. | ||||
| Mouse models | ||||
| β ARK1 overexpression | ↓aβ AR inotropic response; ↑β ARK1 | β ARKct | ↑β AR sensitivity; ↓β ARK1 | (49) |
| bmlp | DCMc ; β AR desensitization | β ARKct | Prevention of DCM; ↑β AR sensitivity | (7) |
| CSQd overexpression | Cardiomyopathy | β ARKct ±β -Blocker | ↓ Cardiomyopathy; ↑ survival | (51) |
| Mutation in MHCe | HCMf | β ARKct | ↓ Cardiomyopathy; ↑ exercise tolerance; ↓ hypertrophic gene expression | (50) |
| CREBA133 expression | DCM; ↓ β AR reserve; ↑β ARK1 | β ARKct | ↑β AR signaling; ↓β ARK1 | (52) |
| Transverse aortic constriction | LVg hypertrophy; β AR desensitization; ↑β ARK1 | CARP–β ARKct | ↑β AR responsiveness | (55) |
| Isoproterenol (β AR-agonist) | Myocardial hypertrophy; ↓β ARK1; ↑β AR signaling | Carvedilol (β -Blocker) | ↑β ARK1; ↓β AR signaling | (45) |
| Ischemia/reperfusion | Ischemic myocardial injury | β ARKct | ↑ Baseline function; ↓ injury | (54) |
| Non-mouse models | ||||
| Sodium deprivation (rat) | Chronic SNSh activation; ↑β ARK1; ↓β AR signaling (without hypertrophy) | β -blocker | ↓β ARK1; ↑β AR signaling | (47) |
| Induced pacing (rabbit) | Failing myocytes; ↓β AR density and signaling; ↑β ARK1 | β ARKct | ↓β ARK1; ↑β AR signaling | (56) |
| Spontaneous hypertensive heart failure (rat) | Failing myocytes; ↓β AR signaling; ↓ contractility | β ARKct | ↑β AR signaling; ↑ contractility | (57) |
| Myocardial infarction (rabbit) | ↓β AR signaling; ↑β ARK1 | β ARKct | ↑β AR signaling; ↓β ARK1; ↑ contractility | (58) |
| Myocardial infarction (rabbit) | ↓β AR signaling; ↓ LV systole | β ARKct | ↑β AR signaling; ↑ systole | (59) |
| Pulmonary artery banding (rabbit) | RVi hypertrophy; death | β ARKct | ↑ Survival | (60) |
| Cardioplegic arrest (rabbit) | ↓ LV function; ↓β AR signaling | β ARKct | ↑β AR signaling; ↑ cardiac function | (61) |
| Heterotropic heart transplant (rabbit) | ↓ Cardiac function | β ARKct | ↑ Cardiac function | (62) |
