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BMC Cardiovascular Disorders
Published in: BMC Cardiovascular Disorders 1/2016

Open Access 01-12-2016 | Research article

Semaphorin 3A attenuates cardiac autonomic disorders and reduces inducible ventricular arrhythmias in rats with experimental myocardial infarction

Authors: Hesheng Hu, Yongli Xuan, Mei Xue, Wenjuan Cheng, Ye Wang, Xinran Li, Jie Yin, Xiaolu Li, Na Yang, Yugen Shi, Suhua Yan

Published in: BMC Cardiovascular Disorders | Issue 1/2016

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Abstract

Background

To investigate the effects of semaphorin 3A (sema 3A) on cardiac autonomic regulation and subsequent ventricular arrhythmias (VAs) in post-infarcted hearts.

Method and results

In order to explore the functions of sema 3A in post-infarcted hearts, lentivirus-Sema 3A-shRNA and negative control vectors were delivered to the peri-infarcted myocardium rats respectively. Meanwhile, recombinant sema 3A and control (0.9 % NaCl solution) were injected intravenously into infarcted rats to test the therapeutic potential of sema 3A. Results indicated that levels of sema 3A were higher in post-infarcted hearts compared with sham rats. However, sema 3A silencing leaded to sympathetic hyperinnervation, increased myocardial norepinephrine (NE) content and inducible VAs. Conversely, the intravenous administration of sema 3A to infarcted rats reduced sympathetic nerve sprouting, improved cardiac autonomic regulation, and decreased the incidence of inducible VAs. However, both infarct size and cardiac function were similar among infarcted hearts.

Conclusions

The upregulation and administration of sema 3A exerted beneficial effects on infarction-induced cardiac autonomic disorders by increasing cardiac electrical stability and reducing VAs. Sema 3A might be a potential therapeutic agent for cardiac autonomic abnormalities induced arrhythmias.
Literature
1.
Exner DV. Noninvasive risk stratification after myocardial infarction: rationale, current evidence and the need for definitive trials. Can J Cardiol. 2009;25:21A–7.PubMedPubMedCentralCrossRef
2.
Kuriachan V, Exner DV. Role of risk stratification after myocardial infarction. Curr Treat Options Cardiovasc Med. 2009;11(1):10–21.PubMedCrossRef
3.
4.
Yan SH, Hu HS, Wang XL, Xing QC, Wang Q, Shi CW, et al. Effects of prolonged metoprolol treatment on neural remodeling and inducible ventricular arrhythmias after myocardial infarction in rabbits. Int J Cardiol. 2007;117(3):317–22.PubMedCrossRef
5.
Wang Y, Liu J, Suo F, Hu HS, Xue M, Cheng WJ, et al. Metoprolol–mediated amelioration of sympathetic nerve sprouting after myocardial infarction. Cardiology. 2013;126(1):50–8.PubMedCrossRef
6.
Chen PS, Chen LS, Cao JM, Sharifi B, Karagueuzian HS, Fishbein MC. Sympathetic nerve sprouting, electrical remodeling and the mechanisms of sudden cardiac death. Cardiovasc Res. 2001;50(2):409–16.PubMedCrossRef
7.
Liu YB, Wu CC, Lu LS, Su MJ, Lin CW, Lin SF, et al. Sympathetic nerve sprouting, electrical remodeling, and increased vulnerability to ventricular fibrillation in hypercholesterolemic rabbits. Circ Res. 2003;92(10):1145–52.PubMedCrossRef
8.
9.
Pruvot E, Thonet G, Vesin JM, van Melle G, Seidl K, Schmidinger H, et al. Heart rate dynamics at the onset of ventricular tachyarrhythmias as retrieved from implantable cardioverter–defibrillators in patients with coronary artery disease. Circulation. 2000;101(20):2398–404.PubMedCrossRef
10.
Malfatto G, Facchini M, Sala L, Branzi G, Bragato R, Leonetti G. Relationship between baseline sympatho-vagal balance and the autonomic response to cardiac rehabilitation after a first uncomplicated myocardial infarction. Ital Heart J. 2000;1(3):226–32.PubMed
11.
Nguyen BL, Li H, Fishbein MC, Lin SF, Gaudio C, Chen PS, et al. Acute myocardial infarction induces bilateral stellate ganglia neural remodeling in rabbits. Cardiovasc Pathol. 2012;21(3):143–8.PubMedPubMedCentralCrossRef
12.
Cao JM, Chen LS, KenKnight BH, Ohara T, Lee MH, Tsai J, et al. Nerve sprouting and sudden cardiac death. Circ Res. 2000;86(7):816–21.PubMedCrossRef
13.
Govoni S, Pascale A, Amadio M, Calvillo L, D’Elia E, Cereda C, et al. NGF and heart: Is there a role in heart disease? Pharmacol Res. 2011;63(4):266–77.PubMedCrossRef
14.
Hu H, Xuan Y, Wang Y, Xue M, Suo F, Li X, et al. Targeted NGF siRNA delivery attenuates sympathetic nerve sprouting and deteriorates cardiac dysfunction in rats with myocardial infarction. PLoS One. 2014;9(4), e95106.PubMedPubMedCentralCrossRef
15.
Goshima Y, Sasaki Y, Yamashita N, Nakamura F. Class 3 semaphorins as a therapeutic target. Expert Opin Ther Targets. 2012;16(9):933–44.PubMedCrossRef
16.
Ieda M, Kanazawa H, Kimura K, Hattori F, Ieda Y, Taniguchi M, et al. Sema3a maintains normal heart rhythm through sympathetic innervation patterning. Nat Med. 2007;13(5):604–12.PubMedCrossRef
17.
Hashimoto M, Ino H, Koda M, Murakami M, Yoshinaga K, Yamazaki M, et al. Regulation of semaphorin 3A expression in neurons of the rat spinal cord and cerebral cortex after transection injury. Acta Neuropathol. 2004;107(3):250–6.PubMedCrossRef
18.
Jiang SX, Whitehead S, Aylsworth A, Slinn J, Zurakowski B, Chan K, et al. Neuropilin 1 directly interacts with Fer kinase to mediate semaphorin 3A-induced death of cortical neurons. J Biol Chem. 2010;285(13):9908–18.PubMedPubMedCentralCrossRef
19.
Chen RH, Li YG, Jiao KL, Zhang PP, Sun Y, Zhang LP, et al. Overexpression of sema3a in myocardial infarction border zone decreases vulnerability of ventricular tachycardia post‐myocardial infarction in rats. J Cell Mol Med. 2013;17(5):608–16.PubMedPubMedCentralCrossRef
20.
Nakano Y, Chayama K, Ochi H, Toshishige M, Hayashida Y, Miki D, et al. A nonsynonymous polymorphism in Semaphorin 3A as a risk factor for human unexplained cardiac arrest with documented ventricular fibrillation. PLoS Genet. 2013;9(4), e1003364.PubMedPubMedCentralCrossRef
21.
Ichim CV, Wells RA. Generation of high-titer viral preparations by concentration using successive rounds of ultracentrifugation. J Transl Med. 2011;9(1):1–8.CrossRef
22.
Saal KA, Koch JC, Tatenhorst L, Szego EM, Ribas VT, Michel U, et al. AAV.shRNA-mediated downregulation of ROCK2 attenuates degeneration of dopaminergic neurons in toxin-induced models of Parkinson’s disease in vitro and in vivo. Neurobiol Dis. 2015;73:150–62.PubMedCrossRef
23.
Nguyen T, El Salibi E, Rouleau JL. Postinfarction survival and inducibility of ventricular arrhythmias in the spontaneously hypertensive rat effects of ramipril and hydralazine. Circulation. 1998;98(19):2074–80.PubMedCrossRef
24.
Lee TM, Chen CC, Hsu YJ. Differential effects of NADPH oxidase and xanthine oxidase inhibition on sympathetic reinnervation in postinfarct rat hearts. Free Radic Biol Med. 2011;50(11):1461–70.PubMedCrossRef
25.
Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative CT method. Nat Protoc. 2008;3(6):1101–8.PubMedCrossRef
26.
Kakinuma Y, Akiyama T, Sato T. Cholinoceptive and cholinergic properties of cardiomyocytes involving an amplification mechanism for vagal efferent effects in sparsely innervated ventricular myocardium. FEBS J. 2009;276(18):5111–25.PubMedCrossRef
27.
Li W, Knowlton D, Van Winkle DM, Habecker BA. Infarction alters both the distribution and noradrenergic properties of cardiac sympathetic neurons. Am J Physiol Heart Circ Physiol. 2004;286(6):H2229–36.PubMedCrossRef
28.
Hayashi M, Nakashima T, Taniguchi M, Kodama T, Kumanogoh A, Takayanagi H. Osteoprotection by semaphorin 3A. Nature. 2012;485(7396):69–74.PubMedCrossRef
29.
30.
Chen LS, Zhou S, Fishbein MC, CHEN PS. New perspectives on the role of autonomic nervous system in the genesis of arrhythmias. J Cardiovasc Electrophysiol. 2007;18(1):123–7.PubMedCrossRef
31.
Lymperopoulos A. Physiology and pharmacology of the cardiovascular adrenergic system. Front Physiol. 2013;4.
32.
Parrish DC, Alston EN, Rohrer H, Hermes SM, Aicher SA, Nkadi P, et al. Absence of gp130 in dopamine β-hydroxylase-expressing neurons leads to autonomic imbalance and increased reperfusion arrhythmias. Am J Physiol Heart Circ Physiol. 2009;297(3):H960–7.PubMedPubMedCentralCrossRef
33.
34.
Kimura K, Ieda M, Fukuda K. Development, maturation, and transdifferentiation of cardiac sympathetic nerves. Circ Res. 2012;110(2):325–36.PubMedCrossRef
35.
Chao MV. Neurotrophins and their receptors: a convergence point for many signalling pathways. Nat Rev Neurosci. 2003;4(4):299–309.PubMedCrossRef
36.
Sun SQ, Wang XT, Qu XF, Li Y, Yu Y, Song Y, et al. Increased expression of myocardial semaphorin 3A in isoproterenol-induced heart failure rats. Chinese Med J-Beijing. 2011;124(14):2173.
37.
Marks AR, Priori S, Memmi M, Kontula K, Laitinen PJ. Involvement of the cardiac ryanodine receptor/calcium release channel in catecholaminergic polymorphic ventricular tachycardia. J Cell Physiol. 2002;190(1):1–6.PubMedCrossRef
38.
Baker KE, Curtis MJ. Left regional cardiac perfusion in vitro with platelet‐activating factor, norepinephrine and K+ reveals that ischaemic arrhythmias are caused by independent effects of endogenous ‘mediators’ facilitated by interactions, and moderated by paradoxical antagonism. Br J Pharmacol. 2004;142(2):352–66.PubMedPubMedCentralCrossRef
39.
Wen HZ, Jiang H, Li L, Xie P, Li JY, Lu ZB, et al. Semaphorin 3A attenuates electrical remodeling at infarct border zones in rats after myocardial infarction. Tohoku J Exp Med. 2011;225(1):51–7.PubMedCrossRef
40.
Naccarella F, Lepera G, Rolli A. Arrhythmic risk stratification of post–myocardial infarction patients. Curr Opin Cardiol. 2000;15(1):1–6.PubMedCrossRef
41.
Tang XQ, Tanelian DL, Smith GM. Semaphorin3A inhibits nerve growth factor-induced sprouting of nociceptive afferents in adult rat spinal cord. J Neurosci. 2004;24(4):819–27.PubMedCrossRef
42.
Reed M, Robertson C, Addison P. Heart rate variability measurements and the prediction of ventricular arrhythmias. QJM. 2005;98(2):87–95.PubMedCrossRef
Metadata
Title
Semaphorin 3A attenuates cardiac autonomic disorders and reduces inducible ventricular arrhythmias in rats with experimental myocardial infarction
Authors
Hesheng Hu
Yongli Xuan
Mei Xue
Wenjuan Cheng
Ye Wang
Xinran Li
Jie Yin
Xiaolu Li
Na Yang
Yugen Shi
Suhua Yan
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Cardiovascular Disorders / Issue 1/2016
Electronic ISSN: 1471-2261
DOI
https://doi.org/10.1186/s12872-016-0192-8

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