Why the study?
To explore whether the protective effect of ACEI on cardiac remodelling and inflammatory immune response after MI is repressed under a hyperlipidemic environment.
Does hyperlipidemia inhibit the cardioprotective effect of lisinopril after myocardial infarction via activation of dendritic cells?
Does hyperlipidemia inhibit the cardioprotective effect of lisinopril after myocardial infarction via activation of dendritic cells?
Hyperlipidemia blunts the cardioprotective effects of ACE inhibitors post-myocardial infarction by promoting dendritic cell-mediated inflammation via the TLR4-MyD88 pathway.
Hyperlipidemia may blunt lisinopril benefits post-MI; hypothesis-generating for TLR4-MyD88 pathways in humans.
To investigate the prevention of cardiac remodelling and inflammatory immune response after myocardial infarction (MI) via ACEI regulating dendritic cells (DCs), we explored whether the protective effect of ACEI was repressed under hyperlipidemic environment. In vivo, the survival rate and left ventricular function of the mice were recorded on day 7 after MI. Tissue samples of the myocardium, spleen, bone marrow and peripheral blood were assessed for Ang II concentration, inflammatory cytokines and DCs expression. In vitro, DCs were treated with ox‐LDL + Ang II, simulating the internal environment of MI in ApoE −/− mice to explore the mechanism involved in the DCs maturation and inflammation. Under hyperlipidemic circumstances, we found that the cardioprotective effect of ACEI was attenuated through regulating DCs maturation and inflammation after MI, affecting survival rate and left ventricular function. Effects of lisinopril on the release of spleen‐derived DCs and myocardial infiltration were also reduced under hyperlipidemic conditions. In vitro, immune maturation and inflammation of DCs were further induced by ox‐LDL on the basis of Ang II treatment, as indicated by the upregulation of CD83, CD86, and the expressions of cytokines and chemokines. Furthermore, ox‐LDL could activate TLR4‐MyD88 signalling pathway, promoting IRAK‐4 and NF‐κB. The present study demonstrated that ACEI reduced the recruitment of DCs to the infarct site, leading to a higher survival rate and improved function. However, this effect was inhibited under hyperlipidemic environment. TLR4‐MyD88 signalling pathway may be responsible for the molecular mechanism involved in the immune maturation and inflammation of DCs induced by ox‐LDL.
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Ma et al. (2020) studied this question.
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