Targeting cardiac β-adrenergic signaling via GRK2 inhibition for heart failure therapy

Frontiers in Physiology

Volumn 4 SEP, Issue , 2013, Pages

  Cannavo, Alessandro ^a   Liccardo, Daniela ^b   Koch, Walter J ^a  

^a TEMPLE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF NAPLES FEDERICO II   (Italy)

Author keywords

adrenergic system; blockers; G protein coupled receptors; G protein coupled receptor kinase 2; Heart failure

Indexed keywords

BETA ADRENERGIC RECEPTOR; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; BETA ADRENERGIC RECEPTOR KINASE; CARDIOVASCULAR AGENT; G PROTEIN COUPLED RECEPTOR; G PROTEIN COUPLED RECEPTOR KINASE 2; G PROTEIN COUPLED RECEPTOR KINASE 2 INHIBITOR; PAROXETINE; PHOSPHOTRANSFERASE INHIBITOR; PROTEIN KINASE B; UNCLASSIFIED DRUG;

ADRENERGIC NERVE; ADRENERGIC RECEPTOR BLOCKING; ADRENERGIC STIMULATION; ADRENERGIC SYSTEM; BRADYCARDIA; CARDIOVASCULAR DISEASE; DEPRESSION; DISEASE COURSE; DIZZINESS; DRUG MECHANISM; DRUG TARGETING; ENZYME ACTIVE SITE; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; ENZYME REGULATION; HEART FAILURE; HEART HYPERTROPHY; HEART INJURY; HEART INNERVATION; HEART MUSCLE CELL; HEART MUSCLE ISCHEMIA; HEART STRESS; HUMAN; HYPOTENSION; NONHUMAN; PATHOPHYSIOLOGY; PROTEIN DEFECT; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN TARGETING; RECEPTOR DOWN REGULATION; REVIEW; SIGNAL TRANSDUCTION; SURVIVAL RATE; UPREGULATION; WEAKNESS;

EID: 84885362278     PISSN: None     EISSN: 1664042X     Source Type: Journal    
DOI: 10.3389/fphys.2013.00264     Document Type: Review

References (69)

1. Aragón, J. P., Condit, M. E., Bhushan, S., Predmore, B. L., Patel, S. S., Grinsfelder, D. B., et al. (2011). Beta 3-adrenoreceptor stimulation ameliorates myocardial ischemia-reperfusion injury via endothelial nitric oxide synthase and neuronal nitric oxide synthase activation. J. Am. Coll. Cardiol. 58, 2683-2691. doi:10.1016/j.jacc.2011.09.033.
2. Barki-Harrington, L., Luttrell, L. M., and Rockman, H. A. (2003). Dual inhibition of beta-adrenergic and angiotensin II receptors by a single antagonist:a functional role for receptor-receptor interaction in vivo. Circulation 108, 1611-1618. doi:10.1161/01.CIR.0000092166.30360.78.
3. Bonacci, T. M., Mathews, J. L., Yuan, C., Lehmann, D. M., Malik, S., Wu, D., et al. (2006). Differential targeting of Gβγ-subunit signaling with small molecules. Science 312, 443-446. doi:10.1126/science.1120378.
4. Braunwald, E. (2001). The Denolin lecture. Congestive heart failure:a half century perspective. Eur. Heart J. 22, 825-836. doi:10.1053/euhj.2001.2614.
5. Brinks, H., Boucher, M., Gao, E., Chuprun, J. K., Pesant, S., Raake, P. W., et al. (2010). Level of G protein-coupled receptor kinase-2 determines myocardial ischemia/reperfusion injury via pro- and anti-apoptotic mechanisms. Circ. Res. 107, 1140-1149. doi:10.1161/CIRCRESAHA.110.221010.
6. Bristow, M. R. (1997). Mechanism of action of beta-blocking agents in heart failure. Am. J. Cardiol. 80, 26L-40L. doi:10.1016/S0002-9149(97)00846-1.
7. Bristow, M. R. (2000). beta-adrenergic receptor blockade in chronic heart failure. Circulation 101, 558-569. doi:10.1161/01.CRI.101.5.558.
8. Bristow, M. R. (2011). Treatment of chronic heart failure with β-adrenergic receptor antagonists:a convergence of receptor pharmacology and clinical cardiology. Circ. Res. 109, 1176-1194. doi:10.1161/CIRCRESAHA.111.245092.
9. Bristow, M. R., Ginsburg, R., Minobe, W., Cubicciotti, R. S., Sageman, W. S., Lurie, K., et al. (1982). Decreased catecholamine sensitivity and β-adrenergic-receptor density in failing human hearts. N. Engl. J. Med. 307, 205-211. doi:10.1056/NEJM198207223070401.
10. Bristow, M. R., Hershberger, R. E., Port, J. D., Gilbert, E. M., Sandoval, A., Rasmussen, R., et al. (1990). Beta-adrenergic pathways in nonfailing and failing human ventricular myocardium. Circulation 82(Suppl. 2), I12-I25.
11. Bristow, M. R., Larrabee, P., Minobe, W., Roden, R., Skerl, L., Klein, J., et al. (1992). Receptor pharmacology of carvedilol in the human heart. J. Cardiovasc. Pharmacol. 19(Suppl. 1), S68-S80. doi:10.1097/00005344-199219001-00014.
12. Casey, L. M., Pistner, A. R., Belmonte, S. L., Migdalovich, D., Stolpnik, O., Nwakanma, F. E., et al. (2010). Small molecule disruption of G beta gamma signaling inhibits the progression of heart failure. Circ. Res. 107, 532-539. doi:10.1161/CIRCRESAHA.110.217075.
13. Chen, M., Sato, P. Y., Chuprun, J. K., Peroutka, R. J., Otis, N. J., Ibetti, J., et al. (2013). Prodeath signaling of G protein-coupled receptor kinase 2 in cardiac myocytes after ischemic stress occurs via extracellular signal-regulated kinase-dependent heat shock protein 90-mediated mitochondrial targeting. Circ. Res. 112, 1121-1134. doi:10.1161/CIRCRESAHA.112.300754.
14. Chidiac, P., Hebert, T. E., Valiquette, M., Dennis, M., and Bouvier, M. (1994). Inverse agonist activity of β-adrenergic antagonists. Mol. Pharmacol. 45, 490-499.
15. Ciccarelli, M., Chuprun, J. K., Rengo, G., Gao, E., Wei, Z., Peroutka, R. J., et al. (2011). G protein-coupled receptor kinase 2 activity impairs cardiac glucose uptake and promotes insulin resistance after myocardial ischemia. Circulation 123, 1953-1962. doi:10.1161/CIRCULATIONAHA.110.988642.
16. Communal, C., Singh, K., Sawyer, D. B., and Colucci, W. S. (1999). Opposing effects of beta(1)- and beta(2)- adrenergic receptors on cardiac myocyte apoptosis:role of a pertussis toxin-sensitive G protein. Circulation 100, 2210-2212. doi:10.1161/01.CIR.100.22.2210.
17. Dandona, P., Karne, R., Ghanim, H., Hamouda, W., Aljada, A., and Magsino, C. H. Jr. (2000). Carvedilol inhibits reactive oxygen species generation by leukocytes and oxidative damage to amino acids. Circulation 101, 122-124. doi:10.1161/01.CIR.101.2.122.
18. Eckhart, A. D., Duncan, S. J., Penn, R. B., Benovic, J. L., Lefkowitz, R. J., and Koch, W. J. (2000). Hybrid transgenic mice reveal in vivo specificity of G protein-coupled receptor kinases in the heart. Circ. Res. 86, 43-50. doi:10.1161/01.RES.86.1.43.
19. Emorine, L. J., Marullo, S., Briend-Sutren, M. M., Patey, G., Tate, K., Delavier-Klutchko, C., et al. (1989). Molecular characterization of the human beta 3-adrenergic receptor. Science 245, 1118-1121. doi:10.1126/science.2570461.
20. Fan, Q., Chen, M., Zuo, L., Shang, X., Huang, M. Z., Ciccarelli, M., et al. (2013). Myocardial ablation of G protein-coupled receptor kinase 2 (GRK2) decreases ischemia/reperfusion injury through an anti-intrinsic apoptotic pathway. PLoS ONE 8:e66234. doi:10.1371/journal.pone.0066234.
21. Ferguson, S. S. (2001). Evolving concepts in G protein-coupled receptor endocytosis:the role in receptor desensitization and signaling. Pharmacol. Rev. 53, 1-24.
22. Freedman, N. J., Liggett, S. B., Drachman, D. E., Pei, G., Caron, M. G., and Lefkowitz, R. J. (1995). Phosphorylation and desensitization of the human beta 1-adrenergic receptor. Involvement of G protein-coupled receptor kinases and cAMP-dependent protein kinase. J. Biol. Chem. 270, 17953-17961.
23. Freeman, K., Lerman, I., Kranias, E. G., Bohlmeyer, T., Bristow, M. R., Lefkowitz, R. J., et al. (2001). Alterations in cardiac adrenergic signaling and calcium cycling differentially affect the progression of cardiomyopathy. J. Clin. Invest. 107, 967-974. doi:10.1172/JCI12083.
24. Frielle, T., Collins, S., Daniel, K. W., Caron, M. G., Lefkowitz, R. J., and Kobilka, B. K. (1987). Cloning of the cDNA for the human beta 1-adrenergic receptor. Proc. Natl. Acad. Sci. U.S.A. 84, 7920-7924. doi:10.1073/pnas.84.22.7920.
25. Harding, V., Jones, L., Lefkowitz, R. J., Koch, W. J., and Rockman, H. A. (2001). Cardiac βARK1 inhibition prolongs survival and augments β blocker therapy in a mouse model of severe heart failure. Proc. Natl. Acad. Sci. U.S.A. 98, 5809-5814. doi:10.1073/pnas.091102398.
26. Hasbi, A., Allouche, S., Sichel, F., Stanasila, L., Massotte, D., Landemore, G., et al. (2000). Internalization and recycling of d-opioid receptor are dependent on a phosphorylation-dephosphorylation mechanism. J. Pharmacol. Exp. Ther. 293, 237-247.
27. Huang, Z. M., Gold, J. I., and Koch, W. J. (2011). G protein-coupled receptor kinases in normal and failing myocardium. Front. Biosci. 16, 3047-3060. doi:10.2741/3898.
28. Hunt, S. A. American College of Cardiology; American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation Management of Heart Failure). (2005). ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult:a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure). J. Am. Coll. Cardiol. 46, e1-e82. doi:10.1016/j.jacc.2005.08.022.
29. Iaccarino, G., Tomhave, E. D., Lefkowitz, R. J., and Koch, W. J. (1998). Reciprocal in vivo regulation of myocardial G protein-coupled receptor kinase expression by beta-adrenergic receptor stimulation and blockade. Circulation 98, 1783-1789. doi:10.1161/01.CIR.98.17.1783.
30. Jaillon, P. (1990). Relevance of intrinsic sympathomimetic activity for beta blockers. Am. J. Cardiol. 66, 21C-23C. doi:10.1016/0002-9149(90)90758-S.
31. Jaski, B. E., Jessup, M. L., Mancini, D. M., Cappola, T. P., Pauly, D. F., Greenberg, B., et al. (2009). Calcium upregulation by percutaneous administration of gene therapy in cardiac disease (CUPID Trial), a first-in-human phase 1/2 clinical trial. Calcium up-regulation by percutaneous administration of gene therapy in cardiac disease (CUPID) trial investigators. J. Card. Fail. 15, 171-181. doi:10.1016/j.cardfail.2009.01.013.
32. Jessup, M., Greenberg, B., Mancini, D., Cappola, T., Pauly, D. F., Jaski, B., et al. (2011). Calcium upregulation by percutaneous administration of gene therapy in cardiac disease (CUPID):a phase 2 trial of intracoronary gene therapy of sarcoplasmic reticulum Ca2+-ATPase in patients with advanced heart failure. Calcium upregulation by percutaneous administration of gene therapy in cardiac disease (CUPID) investigators. Circulation 124, 304-313. doi:10.1161/CIRCULATIONAHA.111.022889.
33. Kassack, M. U., Hogger, P., Gschwend, D. A., Kameyama, K., Haga, T., Graul, R. C., et al. (2000). Molecular modeling of G-protein coupled receptor kinase 2:docking and biochemical evaluation of inhibitors. AAPS Pharmsci. 2, E2. doi:10.1208/ps020102.
34. Keys, J. R., and Koch, W. J. (2004). The adrenergic pathway and heart failure. Recent Prog. Horm. Res. 59, 13-30. doi:10.1210/rp.59.1.13.
35. Kim, C. M., Dion, S. B., Onorato, J. J., and Benovic, J. L. (1993). Expression and characterization of two β-adrenergic receptor kinase isoforms using the baculovirus expression system. Receptor 3, 39-55.
36. Kobilka, B. K., Dixon, R. A., Frielle, T., Dohlman, H. G., Bolanowski, M. A., Sigal, I. S., et al. (1987). cDNA for the human beta 2-adrenergic receptor:a protein with multiple membrane-spanning domains and encoded by a gene whose chromosomal location is shared with that of the receptor for platelet-derived growth factor. Proc. Natl. Acad. Sci. U.S.A. 84, 46-50. doi:10.1073/pnas.84.1.46.
37. Koch, W. J., Inglese, J., Stone, W. C., and Lefkowitz, R. J. (1993). The binding site for the beta gamma subunits of heterotrimeric G proteins on the beta-adrenergic receptor kinase. J. Biol. Chem. 268, 8256-8260.
38. Koch, W. J., Rockman, H. A., Samama, P., Hamilton, R. A., Bond, R. A., Milano, C. A., et al. (1995). Cardiac function in mice overexpressing the beta-adrenergic receptor kinase or a beta ARK inhibitor. Science 268, 1350-1353. doi:10.1126/science.7761854.
39. Leineweber, K., Rohe, P., Beilfuss, A., Wolf, C., Sporkmann, H., Bruck, H., et al. (2005). G-protein coupled receptor kinase activity in human heart failure:effects of beta-adrenoceptor blockade. Cardiovasc. Res. 66, 512-519. doi:10.1016/j.cardiores.2005.01.025.
40. Lohse, M. J., Lefkowitz, R. J., Caron, M. G., and Benovic, J. L. (1989). Inhibition of β-adrenergic receptor kinase prevents rapid homologous desensitization of β 2-adrenergic receptors. Proc. Natl. Acad. Sci. U.S.A. 86, 3011-3015. doi:10.1073/pnas.86.9.3011.
41. Lymperopoulos, A., Rengo, G., and Koch, W. J. (2012). GRK2 inhibition in heart failure:something old, something new. Curr. Pharm. Des. 18, 186-191. doi:10.2174/138161212799040510.
42. Mann, D. L. (1999). Mechanisms and models in heart failure:a combinatorial approach. Circulation 100, 999-1008. doi:10.1161/01.CIR.100.9.999.
43. Matkovich, S. J., Diwan, A., Klanke, J. L., Hammer, D. J., Marreez, Y., Odley, A. M., et al. (2006). Cardiac-specific ablation of G-protein receptor kinase 2 redefines its roles in heart development and beta-adrenergic signaling. Circ. Res. 99, 996-1003. doi:10.1161/01.RES.0000247932.71270.2c.
44. Mayer, G., Wulffen, B., Huber, C., Brockmann, J., Flicke, B., Neumann, L., et al. (2008). An RNA molecule that specifically inhibits G-protein-coupled receptor kinase 2 in vitro. RNA 14, 524-534. doi:10.1261/rna.821908.
45. Morisco, C., Zebrowski, D. C., Vatner, D. E., Vatner, S. F., and Sadoshima, J. (2001). β-adrenergic cardiac hypertrophy is mediated primarilyby the β1-subtype in the rat heart. J. Mol. Cell. Cardiol. 33, 561-573. doi:10.1006/jmcc.2000.1332.
46. Packer, M. (2001). Current role of β-adrenergic blockers in the management of chronic heart failure. Am. J. Med. 110, 81S-94S. doi:10.1016/S0002-9343(01)00676-3.
47. Penela, P., Murga, C., Ribas, C., Lafarga, V., and Mayor, F. Jr. (2010). The complex G protein-coupled receptor kinase 2 (GRK2) interactome unveils new physiopathological targets. Br. J. Pharmacol. 160, 821-832. doi:10.1111/j.1476-5381.2010.00727.x.
48. Piao, L., Fang, Y. H., Parikh, K. S., Ryan, J. J., D'Souza, K. M., Theccanat, T., et al. (2012). GRK2-mediated inhibition of adrenergic and dopaminergic signaling in right ventricular hypertrophy:therapeutic implications in pulmonary hypertension. Circulation 126, 2859-2869. doi:10.1161/CIRCULATIONAHA.112.109868.
49. Pitcher, J. A., Freedman, N. J., and Lefkowitz, R. J. (1998). G protein-coupled receptor kinases. Annu. Rev. Biochem. 67, 653-692. doi:10.1146/annurev.biochem.67.1.653.
50. Pleger, S. T., Shan, C., Kszienyk, J., Bekeredjian, R., Boekstegers, P., Hinkel, R., et al. (2011). Cardiac AAV9-S100A1 gene therapy rescues post-ischemic heart failure in a preclinical large animal model. Sci. Transl. Med. 3, 92ra64. doi:10.1126/scitranslmed.3002097.
51. Raake, P. W., Schlegel, P., Ksienzyk, J., Reinkober, J., Barthelmes, J., Schinkel, S., et al. (2013). AAV6.βARKct cardiac gene therapy ameliorates cardiac function and normalizes the catecholaminergic axis in a clinically relevant large animal heart failure model. Eur. Heart J. 34, 1437-1447. doi:10.1093/eurheartj/ehr447.
52. Raake, P. W., Vinge, L. E., Gao, E., Boucher, M., Rengo, G., Chen, X., et al. (2008). G protein-coupled receptor kinase 2 ablation in cardiac myocytes before or after myocardial infarction prevents heart failure. Circ. Res. 103, 413-422. doi:10.1161/CIRCRESAHA.107.168336.
53. Rengo, G., Lymperopoulos, A., Zincarelli, C., Donniacuo, M., Soltys, S., Rabinowitz, J. E., et al. (2009). Myocardial adeno-associated virus serotype 6-betaARKct gene therapy improves cardiac function and normalizes the neurohormonal axis in chronic heart failure. Circulation 119, 89-98. doi:10.1161/CIRCULATIONAHA.108.803999.
54. Rockman, H. A., Chien, K. R., Choi, D. J., Iaccarino, G., Hunter, J. J., Ross, J. Jr., et al. (1998a). Expression of a beta-adrenergic receptor kinase 1 inhibitor prevents the development of myocardial failure in gene-targeted mice. Proc. Natl. Acad. Sci. U.S.A. 95, 7000-7005. doi:10.1073/pnas.95.12.7000.
55. Rockman, H. A., Choi, D. J., Akhter, S. A., Jaber, M., Giros, B., Lefkowitz, R. J., et al. (1998b). Control of myocardial contractile function by the level of beta-adrenergic receptor kinase 1 in gene-targeted mice. J. Biol. Chem. 273, 18180-18184. doi:10.1074/jbc.273.29.18180.
56. Rockman, H. A., Koch, W. J., and Lefkowitz, R. J. (2002). Seven-transmembrane-spanning receptors and heart function. Nature 415, 206-212. doi:10.1038/415206a.
57. Schafer, M., Frischkopf, K., Taimor, G., Piper, H. M., and Schluter, K. D. (2000). Hypertrophic effect of selective β1-adrenoceptor stimulation on ventricular cardiomyocytes from adult rat. Am. J. Physiol. Cell Physiol. 279, C495-C503.
58. Shah, A. S., White, D. C., Emani, S., Kypson, A. P., Lilly, R. E., Wilson, K., et al. (2001). In vivo ventricular gene delivery of a β-adrenergic receptor kinase inhibitor to the failing heart reverses cardiac dysfunction. Circulation 103, 1311-1316. doi:10.1161/01.CIR.103.9.1311.
59. Tevaearai, H. T., Eckhart, A. D., Shotwell, K. F., Wilson, K., and Koch, W. J. (2001). Ventricular dysfunction following cardioplegic arrest is improved after myocardial gene transfer of a β-adrenergic receptor kinase inhibitor. Circulation 104, 2069-2074. doi:10.1161/hc4201.097188.
60. Thal, D. M., Homan, K. T., Chen, J., Wu, E. K., Hinkle, P. M., Huang, Z. M., et al. (2012). Paroxetine is a direct inhibitor of g protein-coupled receptor kinase 2 and increases myocardial contractility. ACS Chem. Biol. 7, 1830-1839. doi:10.1021/cb3003013.
61. Tritthart, H., Fleckenstein, A., Fleckenstein, B., Herbst, A., and Krause, H. (1969). Quinidine-like action components of beta-receptor antagonists and related substances. Experiments on isolated guinea pig papillary muscles. Naunyn Schmiedebergs Arch. Pharmakol. 264, 317-318. doi:10.1007/BF02431513.
62. Vinge, L. E., Raake, P. W., and Koch, W. J. (2008). Gene therapy in heart failure. Circ. Res. 102, 1458-1470. doi:10.1161/CIRCRESAHA.108.173195.
63. Völkers, M., Weidenhammer, C., Herzog, N., Qiu, G., Spaich, K., von Wegner, F., et al. (2011). The inotropic peptide βARKct improves βAR responsiveness in normal and failing cardiomyocytes through G(βγ)-mediated L-type calcium current disinhibition. Circ. Res. 108, 27-39. doi:10.1161/CIRCRESAHA.110.225201.
64. White, D. C., Hata, J. A., Shah, A. S., Glower, D. D., Lefkowitz, R. J., and Koch, W. J. (2000). Preservation of myocardial beta-adrenergic receptor signaling delays the development of heart failure after myocardial infarction. Proc. Natl. Acad. Sci. U.S.A. 97, 5428-5433. doi:10.1073/pnas.090091197.
65. Winstel, R., Ihlenfeldt, H. G., Jung, G., Krasel, C., and Lohse, M. J. (2005). Peptide inhibitors of G protein-coupled receptor kinases. Biochem. Pharmacol. 70, 1001-1008. doi:10.1016/j.bcp.2005.06.015.
66. Woo, A. Y., and Xiao, R. P. (2012). β-adrenergic receptor subtype signaling in heart:from bench to bedside. Acta Pharmacol. Sin. 33, 335-341. doi:10.1038/aps.2011.201.
67. Xiao, R. P. (2001). Beta-adrenergic signaling in the heart:dual coupling of the beta2-adrenergic receptor to G(s) and G(i) proteins. Sci. STKE 2001, re15. doi:10.1126/stke.2001.104.re15.
68. Zaugg, M., Xu, W., Lucchinetti, E., Shafiq, S. A., Jamali, N. Z., and Siddiqui, M. A. (2000). β-adrenergic receptor subtypes differentially affect apoptosis in adult rat ventricular myocytes. Circulation 102, 344-350. doi:10.1161/01.CIR.102.3.344.
69. Zhu, W. Z., Zheng, M., Koch, W. J., Lefkowitz, R. J., Kobilka, B. K., and Xiao, R. P. (2001). Dual modulation of cell survival and cell death by β2-adrenergic signaling in adult mouse cardiac myocytes. Proc. Natl. Acad. Sci. U.S.A. 98, 1607-1612. doi:10.1073/pnas.98.4.1607.