Immunization with plasmids encoding M2 acetylcholine muscarinic receptor epitopes impairs cardiac function in mice and induces autophagy in the myocardium

References

• Krejčí A, Michal P, Jakubik J, et al. Regulation of signal transduction at M 2 muscarinic receptor. Physiol Res. 2004;53:S131–S140.
   PubMed Web of Science ®Google Scholar
• Matsui S, Fu ML, Shimizu M, et al. Dilated cardiomyopathy defines serum autoantibodies against G-protein-coupled cardiovascular receptors. Autoimmunity. 1995;21:85–88.
   PubMed Web of Science ®Google Scholar
• Fu L-x, Magnusson Y, Bergh C-H, et al. Localization of a functional autoimmune epitope on the muscarinic acetylcholine receptor-2 in patients with idiopathic dilated cardiomyopathy. J Clin Invest. 1993;91:1964–1968.
   PubMed Web of Science ®Google Scholar
• Costa P, Fortes F, Machado A, et al. Sera from chronic chagasic patients depress cardiac electrogenesis and conduction. Braz J Med Biol Res. 2000;33:439–446.
   PubMed Web of Science ®Google Scholar
• Wallukat G, Saravia SGM, Haberland A, et al. Distinct patterns of autoantibodies against g-protein–coupled receptors in chagas' cardiomyopathy and megacolon: their potential impact for early risk assessment in asymptomatic Chagas' patients. J Am Coll Cardiol. 2010;55:463–468.
   PubMed Web of Science ®Google Scholar
• Omerovic E, Bollano E, Andersson B, et al. Induction of cardiomyopathy in severe combined immunodeficiency mice by transfer of lymphocytes from patients with idiopathic dilated cardiomyopathy. Autoimmunity. 2000;32:271–280.
   PubMed Web of Science ®Google Scholar
• Fu ML, Schulze W, Wallukat G, et al. A synthetic peptide corresponding to the second extracellular loop of the human M2 acetylcholine receptor induces pharmacological and morphological changes in cardiomyocytes by active immunization after 6 months in rabbits. Clin Immunol Immunopathol. 1996;78:203–207.
   PubMedGoogle Scholar
• Matsui S, Fu ML, Katsuda S, et al. Peptides derived from cardiovascular G-protein-coupled receptors induce morphological cardiomyopathic changes in immunized rabbits. J Mol Cell Cardiol. 1997;29:641–655.
   PubMed Web of Science ®Google Scholar
• Elies R, Fu L, Eftekhari P, et al. Immunochemical and functional characterization of an agonist‐like monoclonal antibody against the M2 acetylcholine receptor. Eur J Biochem. 1998;251:659–666.
   PubMedGoogle Scholar
• Hernández CCQ, Barcellos LC, Giménez LED, et al. Human chagasic IgGs bind to cardiac muscarinic receptors and impair L-type Ca2+ currents. Cardiovasc Res. 2003;58:55–65.
   PubMed Web of Science ®Google Scholar
• Hernández CC, Nascimento JH, Chaves EA, et al. Autoantibodies enhance agonist action and binding to cardiac muscarinic receptors in chronic Chagas' disease. J Recept Signal Transduct. 2008;28:375–401.
   PubMed Web of Science ®Google Scholar
• Retondaro F, Dos Santos Costa P, Pedrosa R, et al. Presence of antibodies against the third intracellular loop of the m2 muscarinic receptor in the sera of chronic chagasic patients. Faseb J. 1999;13:2015–2020.
   PubMed Web of Science ®Google Scholar
• Giménez LE, Hernández CC, Mattos EC, et al. DNA immunizations with M2 muscarinic and beta1 adrenergic receptor coding plasmids impair cardiac function in mice. J Mol Cell Cardiol. 2005;38:703–714.
   PubMed Web of Science ®Google Scholar
• Jahns R, Boivin V, Schwarzbach V, et al. Pathological autoantibodies in cardiomyopathy. Autoimmunity. 2008;41:454–461.
   PubMed Web of Science ®Google Scholar
• Martinez CG, Zamith-Miranda D, Da Silva MG, et al. P2X7 purinergic signaling in dilated cardiomyopathy induced by auto-immunity against muscarinic M 2 receptors: autoantibody levels, heart functionality and cytokine expression. Sci Rep. 2015;5:16940.
   PubMed Web of Science ®Google Scholar
• Rose NR, Bona C. Defining criteria for autoimmune diseases (Witebsky's postulates revisited). Immunol Today. 1993;14:426–430.
   PubMedGoogle Scholar
• Zhang S, He Z, Wang J, et al. Mitochondrial ultrastructural alterations and declined M2 receptor density were involved in cardiac dysfunction in rats after long term treatment with autoantibodies against M2 muscarinic receptor. PLoS One. 2015;10:e0129563.
   PubMed Web of Science ®Google Scholar
• Wilson DJ, North N, Wilson RA. Comparison of left ventricular ejection fraction calculation methods. Echocardiography. 1998;15:709–712.
   PubMedGoogle Scholar
• Lappé JM, Pelfrey CM, Tang WW. Recent insights into the role of autoimmunity in idiopathic dilated cardiomyopathy. J Card Fail. 2008;14:521–530.
   PubMed Web of Science ®Google Scholar
• Fairweather D, Rose NR. Inflammatory heart disease: a role for cytokines. Lupus. 2005;14:646–651.
   PubMed Web of Science ®Google Scholar
• Jahns R, Boivin V, Hein L, et al. Direct evidence for a beta 1-adrenergic receptor-directed autoimmune attack as a cause of idiopathic dilated cardiomyopathy. J Clin Invest. 2004;113:1419–1429.
   PubMed Web of Science ®Google Scholar
• Zuo L, Bao H, Tian J, et al. Long-term active immunization with a synthetic peptide corresponding to the second extracellular loop of β1-adrenoceptor induces both morphological and functional cardiomyopathic changes in rats. Int J Cardiol. 2011;149:89–94.
   PubMed Web of Science ®Google Scholar
• Yoshizawa A, Nagai S, Baba Y, et al. Autoimmunity against M2 muscarinic acetylcholine receptor induces myocarditis and leads to a dilated cardiomyopathy like phenotype. Eur J Immunol. 2012;42:1152–1163.
   PubMed Web of Science ®Google Scholar
• Okazaki T, Tanaka Y, Nishio R, et al. Autoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice. Nat Med. 2003;9:1477–1483.
   PubMed Web of Science ®Google Scholar
• Kurtenbach E, Martinez CG. IFN-γ versus IL-17: a battle during cardiac autoimmunity evolution. In: Mourad A, editor. Immunopathogenesis and immune-based therapy for selected autoimmune disorders. London: IntechOpen; 2017. Available from: https://www.intechopen.com/books/immunopathogenesis-and-immune-based-therapy-for-selected-autoimmune-disorders/ifn-versus-il-17-a-battle-during-cardiac-autoimmunity-evolution
   Google Scholar
• Nussinovitch U, Shoenfeld Y. The diagnostic and clinical significance of anti-muscarinic receptor autoantibodies. Clin. Clinic Rev Allerg Immunol. 2012;42:298–308.
   PubMed Web of Science ®Google Scholar
• Levin MJ, Hoebeke J. Cross-talk between anti-beta1-adrenoceptor antibodies in dilated cardiomyopathy and Chagas' heart disease. Autoimmunity. 2008;41:429–433.
   PubMed Web of Science ®Google Scholar
• Munoz-Saravia SG, Haberland A, Wallukat G, et al. Chronic Chagas’ heart disease: a disease on its way to becoming a worldwide health problem: epidemiology, etiopathology, treatment, pathogenesis and laboratory medicine. Heart Fail Rev. 2012;17:45–64.
   PubMed Web of Science ®Google Scholar
• del Corsso C, de Carvalho ACC, Martino HF, et al. Sera from patients with idiopathic dilated cardiomyopathy decrease I Ca in cardiomyocytes isolated from rabbits. Am J Physiol Heart Circ Physiol. 2004;287:H1928–H1936.
   PubMed Web of Science ®Google Scholar
• Jiang H, Cheng D, Liu W, et al. Protein kinase C inhibits autophagy and phosphorylates LC3. Bioch Biophys Res Commun. 2010;395:471–476.
   PubMed Web of Science ®Google Scholar
• Jane-wit D, Altuntas CZ, Johnson JM, et al. Beta 1-adrenergic receptor autoantibodies mediate dilated cardiomyopathy by agonistically inducing cardiomyocyte apoptosis. Circulation. 2007;116:399–410.
   PubMed Web of Science ®Google Scholar
• Hoppel CL, Tandler B, Fujioka H, et al. Dynamic organization of mitochondria in human heart and in myocardial disease. International J Biochem Cell Biol. 2009;41:1949–1956.
   PubMed Web of Science ®Google Scholar
• Dutta D, Calvani R, Bernabei R, et al. Contribution of impaired mitochondrial autophagy to cardiac aging: mechanisms and therapeutic opportunities. Circ Res. 2012;110:1125–1138.
   PubMed Web of Science ®Google Scholar
• Lee Y, Lee H-Y, Gustafsson ÅB. Regulation of autophagy by metabolic and stress signaling pathways in the heart. J Cardiovasc Pharmacol. 2012;60:118–124.
   PubMed Web of Science ®Google Scholar
• Baek K-H, Park J, Shin I. Autophagy-regulating small molecules and their therapeutic applications. Chem Soc Rev. 2012;41:3245–3263.
   PubMed Web of Science ®Google Scholar
• Shoji-Kawata S, Sumpter R, Leveno M, et al. Identification of a candidate therapeutic autophagy-inducing peptide. Nature. 2013;494:201–206.
   PubMed Web of Science ®Google Scholar
• Zhao M, Sun L, Yu X-J, et al. Acetylcholine mediates AMPK-dependent autophagic cytoprotection in H9c2 cells during hypoxia/reoxygenation injury. Cell Physiol Biochem. 2013;32:601–613.
   PubMed Web of Science ®Google Scholar
• Bhuiyan MS, Pattison JS, Osinska H, et al. Enhanced autophagy ameliorates cardiac proteinopathy. J Clin Invest. 2013;123:5284–5297.
   PubMed Web of Science ®Google Scholar
• Nair S, Ren J. Autophagy and cardiovascular aging: lesson learned from rapamycin. Cell Cycle. 2012;11:2092–2099.
   PubMed Web of Science ®Google Scholar
• Saito T, Asai K, Sato S, et al. Autophagic vacuoles in cardiomyocytes of dilated cardiomyopathy with initially decompensated heart failure predict improved prognosis. Autophagy 2016;12:579–587.
   PubMed Web of Science ®Google Scholar
• Riehle C, Wende AR, Sena S, et al. Insulin receptor substrate signaling suppresses neonatal autophagy in the heart. J Clin Invest. 2013;123:5319–5333.
   PubMed Web of Science ®Google Scholar
• Mizushima N, Levine B, Cuervo AM, et al. Autophagy fights disease through cellular self-digestion. Nature. 2008;451:1069–1075.
   PubMed Web of Science ®Google Scholar
• Matsui S, Fu M, Hayase M, et al. Transfer of immune components from rabbit autoimmune cardiomyopathy into severe combined immunodeficiency (SCID) mice induces cardiomyopathic changes. Autoimmunity. 2006;39:121–128.
   PubMed Web of Science ®Google Scholar
• Pyle WG, Solaro RJ. At the crossroads of myocardial signaling: the role of Z-discs in intracellular signaling and cardiac function. Circ Res. 2004;94:296–305.
   PubMed Web of Science ®Google Scholar
• Knöll R, Buyandelger B. Z-disc Transcriptional coupling, sarcomeroptosis and mechanopoptosis. Cell Biochem Biophys. 2013;66:65–71.
   PubMed Web of Science ®Google Scholar
• Hoshijima M. Mechanical stress-strain sensors embedded in cardiac cytoskeleton: Z disk, titin, and associated structures. Am J Physiol Heart and Circ Physiol. 2006;290:H1313–H1325.
   PubMed Web of Science ®Google Scholar
• Kant S, Krull P, Eisner S, et al. Histological and ultrastructural abnormalities in murine desmoglein 2-mutant hearts. Cell Tissue Res. 2012;348:249–259.
   PubMed Web of Science ®Google Scholar
• Kostin S, Pool L, Elsässer A, et al. Myocytes die by multiple mechanisms in failing human hearts. Circ Res. 2003;92:715–724.
   PubMed Web of Science ®Google Scholar