Effect of Sympathetic Remodeling on Post-myocardial Infarction Arrhythmias by Regulating the Expression of Sema3a and NGF
WANG Haixiong
LI Jun
LIN Yaru
LI Na
ZHANG Anxin
SUN Yuehui
GUO Liping
YU Xingyan
XIANG Jie
Abstract：Objective:To explore the post-infarction sympathetic nerve regeneration and remodeling in mice,and to artificially regulate the related factors in order to reduce the fatal arrhythmias and sudden cardiac death(SCD) triggered by post-infarction sympathetic nerve pathological remodeling.Methods:Three mouse strain models were established using techniques such as CRISPR/Cas9 and knock-in to compare with wild-type C57BL/6J infarction mice,based on these models coronary arteries were ligated to cause infarction,and the dynamic and balanced expression of nerve growth factor ( NGF) and Semaphorin 3a ( Sema3a) was artificially regulated in myocardial cells after myocardial infarction. Results:Compared with wild type sham operation group,systolic blood pressure(SBP),diastolic blood pressure(DBP),mean arterial pressure(MBP) in wild type myocardial infarction group were decreased(P<0.05),and left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),heart/body weight ratio(HW/BW) were increased(P<0.05).SBP,DBP,MBP in NGF-Sema3a infarction group were decreased and LVESD was increased compared with those in NGF-Sema3a sham operation group (P<0.05). Compared with wild-type mice,LVEDD and LVESD of NGF-Sema3a myocardial infarction group were decreased (P<0.001),left ventricular fraction shortening ( FS) and ejection fraction ( EF) were increased(P<0.05).Compared with wild-type myocardial infarction group,the HW/BW in NGF-Sema3a myocardial infarction group was decreased(P<0.05),the infarct area was smaller,the inflammatory reaction was lighter,and the cell profile was clearer. Conclusion:By regulating the dynamic and balanced expression of NGF and Sema3a in myocardial cell can reduce infarct size,attenuate myocardial inflammation and fibrosis,decrease mortality,and improve cardiac function.
Keywords：sudden cardiac deathmyocardial infarctionarrhythmiaSemaphorin 3anerve growth factorexperimental study
Publication Date：2024-12-16
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：9( 4468-4476 )