The aim of this study was to explore the role and mechanisms of electroacupuncture (EA) in the regulation of chemokines in endogenous stem cell mobilization and myocardial regeneration after myocardial infarction (MI).
Methods:
An MI model was constructed in adult male Sprague-Dawley rats by ligating the left anterior descending coronary artery. After 4 weeks of treatment, echocardiography was used to detect changes in cardiac function, and Masson’s trichrome staining was used to detect collagen deposition. In addition, immunofluorescence staining was applied to examine von Willebrand factor (vWF)-positive vessels, the expression of cardiac troponin T (cTnT) and proliferation marker Ki67, and the number of c-kit-positive, C-X-C chemokine receptor type 4 (CXCR4)-positive, and Sca-1-positive endogenous stem cells in the infarcted area. In addition, the expression of stromal cell-derived factor (SDF)-1 and stem cell factor (SCF) was detected.
Results:
EA increased the ejection fraction after MI, reduced collagen deposition and cellular apoptosis, and increased the number of blood vessels compared with an untreated model group. EA significantly promoted cellular proliferation, except for myocardial cells, and significantly increased the number of c-kit-, CXCR4- and Sca-1-positive stem cells. Moreover, the expression of SDF-1 and SCF in myocardial tissue in the EA group was significantly higher than that in the (untreated) MI group.
Conclusions:
EA appears to promote angiogenesis and reduce collagen deposition, thus improving the cardiac function of rats with MI. The underlying mechanism of action may involve endogenous stem cell mobilization mediated by SDF-1/CXCR4 and SCF/c-kit.
LuSFWangJMYuanJ, et al. Electroacupuncture improves cardiac function and reduces infarct size by modulating cardiac autonomic remodeling in a mouse model of myocardial ischemia. Acupunct Med2021; 39(6): 681–690.
2.
LiZWangCMakAF, et al. Effects of acupuncture on heart rate variability in normal subjects under fatigue and non-fatigue state. Eur J Appl Physiol2005; 94(5–6): 633–640.
3.
SarkarASahaSPaulA, et al. Understanding stem cells and its pivotal role in regenerative medicine. Life Sci2021; 273: 119270.
4.
LunaGPaezJCardierJE. Expression of the hematopoietic stem cell antigen Sca-1 (LY-6A/E) in liver sinusoidal endothelial cells: possible function of Sca-1 in endothelial cells. Stem Cells Dev2004; 13(5): 528–535.
5.
ArjmandBAbediMArabiM, et al. Regenerative medicine for the treatment of ischemic heart disease; status and future perspectives. Front Cell Dev Biol2021; 9: 704903.
6.
VagnozziRJMailletMSargentMA, et al. An acute immune response underlies the benefit of cardiac stem cell therapy. Nature2020; 577(7790): 405–409.
7.
XingSTianJZYangSH, et al. Setd4 controlled quiescent c-Kit+ cells contribute to cardiac neovascularization of capillaries beyond activation. Sci Rep2021; 11: 11603.
8.
LiJLiSHWuJ, et al. Young bone marrow Sca-1 cells rejuvenate the aged heart by promoting epithelial-to-mesenchymal transition. Theranostics2018; 8: 1766–1781.
9.
AleASiebenhaarFKosankeK, et al. Cardioprotective C—kit⁺ bone marrow cells attenuate apoptosis after acute myocardial infarction in mice—in-vivo assessment with fluorescence molecular imaging. Theranostics2013; 3(11): 903–913.
BhaktaSHongPKocO. The surface adhesion molecule CXCR4 stimulates mesenchymal stem cell migration to stromal cell-derived factor-1 in vitro but does not decrease apoptosis under serum deprivation. Cardiovasc Revasc Med2006; 7: 19–24.
12.
VeschiVVeronaFThieleCJ. Cancer stem cells and neuroblastoma: characteristics and therapeutic targeting options. Front Endocrinol2019; 10: 782.
13.
IshikawaKFishKAgueroJ, et al. Stem cell factor gene transfer improves cardiac function after myocardial infarction in swine. Circ Heart Fail2015; 8(1): 167–174.
14.
FazelSCiminiMChenL, et al. Cardioprotective c-kit+ cells are from the bone marrow and regulate the myocardial balance of angiogenic cytokines. J Clin Invest2006; 116(7): 1865–1877.
15.
ParkSJKimRYParkBW, et al. Dual stem cell therapy synergistically improves cardiac function and vascular regeneration following myocardial infarction. Nat Commun2019; 10: 3123.
16.
ZhuJChenZMengZ, et al. Electroacupuncture alleviates surgical trauma-induced hypothalamus pituitary adrenal axis hyperactivity via microRNA-142. Front Mol Neurosci2017; 10: 308.
17.
ChenZXLiYZhangXG, et al. Sham electroacupuncture methods in randomized controlled trials. Sci Rep2017; 7: 40837.
18.
GaoFWuSBCaoJ, et al. Effects of electroacupuncture along heart channel and pericardium channel on amplitudes of J point and T wave of electrocardiogram and on myocardial infarction area in rats with acute myocardial ischemia. J Anhui Univ Chin Med2011; 30: 53–56 (in Chinese).
19.
ChenLWuQFDengSF, et al. Review on mechanism about acupuncture improving myocardial ischemia based on different molecular levels. Liaoning J Trad Chin Med2016; 43: 199–202 (in Chinese).
20.
LiPTjen-A-LooiSC. Mechanism of the inhibitory effect of electroacupuncture on experimental arrhythmias. J Acupunct Meridian Stud2013; 6(2): 69–81.
21.
TsouMTHuangCHChiuJH. Electroacupuncture on PC6 (Neiguan) attenuates ischemia/reperfusion injury in rat hearts. Am J Chin Med2004; 32(6): 951–965.
22.
DongBLiCZhangX, et al. Electroacupuncture of neiguan (PC 6) inhibits enhanced voltage-gated sodium currents in ischemic ventricular myocytes. J Tradit Chin Med2014; 34(6): 710–715.
23.
ZhangZChenMZhangL, et al. Meta-analysis of acupuncture therapy for the treatment of stable angina pectoris. Int J Clin Exp Med2015; 8: 5112–5120.
24.
WuCYJiaLHLuZJ. Effect of warm acupuncture and moxibustion on attack frequency of angina and resting ECG of coronary heart disease. J Clin Acupunct Moxibust2009; 25: 32–34 (in Chinese).
25.
LuJL. Clinical analgesic effect of acupuncture for chronic stable angina pectoris based on acupoints along meridians with location differentiation. Chengdu, China: Chengdu University, 2015 (in Chinese).
26.
ChoSYLeeDHShinHS, et al. The efficacy and safety of acupuncture for cerebral vasospasm after subarachnoid hemorrhage: study protocol for a randomized controlled trial. Trials2015; 16: 68.
27.
YuZLuoLLiY, et al. Different manual manipulations and electrical parameters exert different therapeutic effects of acupuncture. J Tradit Chin Med2014; 34(6): 754–758.
28.
LiTTangBQZhangWB, et al. In vivo visualization of the pericardium meridian with fluorescent dyes. Evid Based Complement Alternat Med2021; 2021: 5581227.
29.
ZhangJX. System of channels and collaterals constituted by different kinds of stem cell niche in ordinal distribution. Shanghai J Acupunct Moxibust2006; 2006: 40 (in Chinese).
30.
HenningRJ. Current status of stem cells in cardiac repair. Future Cardiol2018; 14: 181–192.
31.
GhanimatiRRajabiHRamezaniF, et al. The effect of preconditioning with high-intensity training on tissue levels of G-CSF, its receptor and C-kit after an acute myocardial infarction in male rats. BMC Cardiovasc Disord2020; 20: 75.
32.
WangXHuQNakamuraY, et al. The role of the sca-1+/CD31- cardiac progenitor cell population in postinfarction left ventricular remodeling. Stem Cells2006; 24(7): 1779–1788.
33.
BaileyBFransioliJGudeNA, et al. Sca-1 knockout impairs myocardial and cardiac progenitor cell function. Circ Res2012; 111: 750–760.
34.
AcevesJLLópezRVTeránPM, et al. Autologous CXCR4+ hematopoietic stem cells injected into the scar tissue of chronic myocardial infarction patients normalizes tissue contractility and perfusion. Arch Med Res2020; 51(2): 135–144.
35.
HuangWWangTZhangD, et al. Mesenchymal stem cells overexpressing CXCR4 attenuate remodeling of postmyocardial infarction by releasing matrix metalloproteinase-9. Stem Cells Dev2012; 21: 778–789.
36.
LiuLYuQHuK, et al. Electro-acupuncture promotes endogenous multipotential mesenchymal stem cell mobilization into the peripheral blood. Cell Physiol Biochem2016; 38(4): 1605–1617.
37.
YamaguchiJKusanoKFMasuoO, et al. Stromal cell-derived factor-1 effects on ex vivo expanded endothelial progenitor cell recruitment for ischemic neovascularization. Circulation2003; 107: 1322–1328.
38.
De FalcoEPorcelliDTorellaAR, et al. SDF-1 involvement in endothelial phenotype and ischemia-induced recruitment of bone marrow progenitor cells. Blood2004; 104: 3472–3482.
39.
WynnRFHartCACorradi-PeriniC, et al. A small proportion of mesenchymal stem cells strongly expresses functionally active CXCR4 receptor capable of promoting migration to bone marrow. Blood2004; 104: 2643–2645.
40.
LiLWuSLiuZ, et al. Ultrasound-targeted microbubble destruction improves the migration and homing of mesenchymal stem cells after myocardial infarction by upregulating SDF-1/CXCR4: a pilot study. Stem Cells Int2015; 2015: 691310.
41.
HatzistergosKESaurDSeidlerB, et al. Stimulatory effects of mesenchymal stem cells on cKit+ cardiac stem cells are mediated by SDF1/CXCR4 and SCF/cKit signaling pathways. Circ Res2016; 119: 921–930.
42.
WangWShuiLLiuY, et al. C-Kit, a double-edged sword in liver regeneration and diseases. Front Genet2021; 12: 598855.
43.
SunJZhaoYLiQ, et al. Controlled release of collagen-binding SDF-1α improves cardiac function after myocardial infarction by recruiting endogenous stem cells. Sci Rep2016; 6: 26683.
44.
BogoslovskyTSpatzMChaudhryA, et al. Stromal-derived factor-1[alpha] correlates with circulating endothelial progenitor cells and with acute lesion volume in stroke patients. Stroke2011; 42(3): 618–625.
45.
KwonSGParkIKwonYW, et al. Role of stem cell mobilization in the treatment of ischemic diseases. Arch Pharm Res2019; 42(3): 224–231.
46.
FuSPHeSYXuB, et al. Acupuncture promotes angiogenesis after myocardial ischemia through H3K9 acetylation regulation at VEGF gene. PLoS ONE2014; 9(4): e94604.
47.
ToosizadehNLeiHSchwenkM, et al. Does integrative medicine enhance balance in aging adults? Proof of concept for the benefit of electroacupuncture therapy in Parkinson’s disease. Gerontology2015; 61(1): 3–14.
48.
LangevinHMSchnyerRMacPhersonH, et al. Manual and electrical needle stimulation in acupuncture research: pitfalls and challenges of heterogeneity. J Altern Complement Med2015; 21(3): 113–128.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
