Research progress in regulation of heart failure by β-adrenergic-receptor-PKA-AKAP signaling pathway

doi:10.12092/j.issn.1009-2501.2018.05.018

Abstract

Abstract:

Heart failure is the final stage of the development of various cardiovascular diseases. Because of its high mortality rate and poor prognosis, it has become a major disease that endangers human life and health. In heart failure, the sympathetic system is activated and the catecholamines stimulate β-adrenergic receptor (β-AR) to increase cardiac output via Gs-AC-cAMP-PKA signaling pathway, which is beneficial in the acute phase, but chronic β-ARs stimulation eventually leads to a diminished contractile performance of the heart. A-kinase anchoring protein (AKAP) plays an important role in this pathological process, which regulates signaling pathways by anchoring PKA in specific subcellular locations. β-blockers are widely used in the treatment of heart failure, but also have a range of side effects.Therefore, novel and more targeted therapeutic treatments are needed to improve treatment of HF in the future.

Key words: kinase anchoring protein, heart failure, protein kinase A, β-adrenergic receptor

CLC Number:

R541.6

HUANG Ting, WANG Hegui. Research progress in regulation of heart failure by β-adrenergic-receptor-PKA-AKAP signaling pathway[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(5): 592-596.

References

［1］Bers DM. Cardiac excitation-contraction coupling［J］. Nature, 2002,415(6868):198-205.
［2］Baker AJ. Adrenergic signaling in heart failure: a balance of toxic and protective effects［J］. Pflugers Arch, 2014,466(6):1139-1150.
［3］Vassilatis DK, Hohmann JG, Zeng H, et al. The G protein-coupled receptor repertoires of human and mouse［J］. Proc Natl Acad Sci U S A, 2003,100(8):4903-4908.
［4］Cannavo A, Liccardo D, Koch WJ. Targeting cardiac beta-adrenergic signaling via GRK2 inhibition for heart failure therapy［J］. Front Physiol, 2013,4:264.
［5］Moniotte S, Kobzik L, Feron O, et al. Upregulation of beta(3)-adrenoceptors and altered contractile response to inotropic amines in human failing myocardium［J］. Circulation, 2001,103(12):1649-1655.
［6］Xiang Y, Kobilka BK. Myocyte adrenoceptor signaling pathways.［J］. Science (New York, N.Y.), 2003,300(5625):1530-1532.
［7］Kuster DW, Bawazeer AC, Zaremba R, et al. Cardiac myosin binding protein C phosphorylation in cardiac disease［J］. J Muscle Res Cell Motil, 2012,33(1):43-52.
［8］Stelzer JE, Patel JR, Walker JW, et al. Differential roles of cardiac myosin-binding protein C and cardiac troponin I in the myofibrillar force responses to protein kinase A phosphorylation［J］. Circ Res, 2007,101(5):503-511.
［9］Yamasaki R, Wu Y, McNabb M, et al. Protein kinase A phosphorylates titin's cardiac-specific N2B domain and reduces passive tension in rat cardiac myocytes［J］. Circ Res, 2002,90(11):1181-1188.
［10］Ginsburg KS, Bers DM. Modulation of excitation-contraction coupling by isoproterenol in cardiomyocytes with controlled SR Ca2+ load and Ca2+ current trigger［J］. J Physiol, 2004,556(Pt 2):463-480.
［11］van der Heyden MA,Wijnhoven TJ,Opthof T.Molecular aspects of adrenergic modulation of cardiac L-type Ca2+ channels［J］.Cardiovasc Res,2005,65(1):28-39.
［12］Ruehr ML, Russell MA, Bond M. A-kinase anchoring protein targeting of protein kinase A in the heart［J］. J Mol Cell Cardiol, 2004,37(3):653-665.
［13］Diviani D, Maric D, Perez LI, et al. A-kinase anchoring proteins: molecular regulators of the cardiac stress response［J］. Biochim Biophys Acta, 2013,1833(4):901-908.
［14］Skroblin P, Grossmann S, Schafer G, et al. Mechanisms of protein kinase A anchoring［J］. Int Rev Cell Mol Biol, 2010,283:235-330.
［15］Di Benedetto G, Zoccarato A, Lissandron V, et al. Protein kinase A type I and type II define distinct intracellular signaling compartments［J］. Circ Res, 2008,103(8):836-844.
［16］Barradeau S, Imaizumi-Scherrer T, Weiss MC, et al. Intracellular targeting of the type-I alpha regulatory subunit of cAMP-dependent protein kinase［J］. Trends Cardiovasc Med, 2002,12(6):235-241.
［17］Xiang YK. Compartmentalization of beta-adrenergic signals in cardiomyocytes［J］. Circ Res, 2011,109(2):231-244.
［18］Stangherlin A, Gesellchen F, Zoccarato A, et al. cGMP signals modulate cAMP levels in a compartment-specific manner to regulate catecholamine-dependent signaling in cardiac myocytes［J］. Circ Res, 2011,108(8):929-939.
［19］Bers DM, Ziolo MT. When is cAMP not cAMP? Effects of compartmentalization［J］. Circ Res, 2001,89(5):373-375.
［20］Lygren B, Carlson CR, Santamaria K, et al. AKAP complex regulates Ca2+ re-uptake into heart sarcoplasmic reticulum［J］. EMBO Rep, 2007,8(11):1061-1067.
［21］Sumandea CA, GarciaCazarin ML, Bozio CH, et al. Cardiac troponin T, a sarcomeric AKAP, tethers protein kinase A at the myofilaments［J］. J Biol Chem, 2011,286(1):530-541.
［22］Uys GM, Ramburan A, Loos B, et al. Myomegalin is a novel A-kinase anchoring protein involved in the phosphorylation of cardiac myosin binding protein C［J］. BMC Cell Biol, 2011,12:18.
［23］Hundsrucker C, Klussmann E. Direct AKAP-mediated protein-protein interactions as potential drug targets［J］. Handb Exp Pharmacol, 2008(186):483-503.
［24］Ryall JG, Schertzer JD, Murphy KT, et al. Chronic beta2-adrenoceptor stimulation impairs cardiac relaxation via reduced SR Ca2+-ATPase protein and activity［J］. Am J Physiol Heart Circ Physiol, 2008,294(6):H2587-H2595.
［25］Dessauer CW. Adenylyl cyclase-A-kinase anchoring protein complexes: the next dimension in cAMP signaling［J］. Mol Pharmacol, 2009,76(5):935-941.
［26］McMurray JJ, Adamopoulos S, Anker S D, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The task force for the diagnosis and treatment of acute and chronic heart failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC［J］. Eur Heart J, 2012,33(14):1787-1847.
［27］Brophy JM, Joseph L, Rouleau JL. Beta-blockers in congestive heart failure. A Bayesian meta-analysis［J］. Ann Intern Med, 2001,134(7):550-560.
［28］Teerlink JR, Massie BM. The role of beta-blockers in preventing sudden death in heart failure［J］. J Card Fail, 2000,6(2 Suppl 1):25-33.
［29］Khan N, McAlister FA. Re-examining the efficacy of beta-blockers for the treatment of hypertension: a meta-analysis［J］. CMAJ, 2006,174(12):1737-1742.
［30］Messerli FH, Beevers DG, Franklin SS, et al. beta-Blockers in hypertension-the emperor has no clothes: an open letter to present and prospective drafters of new guidelines for the treatment of hypertension［J］. Am J Hypertens, 2003,16(10):870-873.
［31］Liang M, Puri A, Devlin G. Heart rate and cardiovascular disease: an alternative to Beta blockers［J］. Cardiol Res Pract, 2009,2009:179350.
［32］Malik FI, Hartman JJ, Elias KA, et al. Cardiac myosin activation: a potential therapeutic approach for systolic heart failure［J］. Science, 2011,331(6023):1439-1443.
［33］Orstavik O, Ata SH, Riise J, et al. Inhibition of phosphodiesterase-3 by levosimendan is sufficient to account for its inotropic effect in failing human heart［J］. Br J Pharmacol, 2014,171(23):5169-5181.
［34］Mebazaa A, Barraud D, Welschbillig S. Randomized clinical trials with levosimendan［J］. Am J Cardiol, 2005,96(6A):74G-79G.
［35］Passino C, Severino S, Poletti R, et al. Aerobic training decreases B-type natriuretic peptide expression and adrenergic activation in patients with heart failure［J］. J Am Coll Cardiol, 2006,47(9):1835-1839.
［36］Lavie CJ, Arena R, Swift DL, et al. Exercise and the cardiovascular system: clinical science and cardiovascular outcomes［J］. Circ Res, 2015,117(2):207-219.
［37］Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines［J］. J Am Coll Cardiol, 2013,62(16):e147-e239.
［38］McConnell BK, Popovic Z, Mal N, et al. Disruption of protein kinase A interaction with A-kinase-anchoring proteins in the heart in vivo: effects on cardiac contractility, protein kinase A phosphorylation, and troponin I proteolysis［J］. J Biol Chem, 2009,284(3):1583-1592.

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