Key result
Myeloid SHP2 knockout improves cardiac function and reduces infarct size in post-MI mice.
Why the study?
To evaluate the effects of myeloid-specific knockout of SHP2 on early myocardial infarction and elucidate its underlying molecular mechanism.
Myeloid-specific knockout of SHP2 protects against early myocardial infarction injury by modulating macrophage phagocytosis and inflammation via the PI3K/PLCγ pathway.
Myeloid SHP2 knockout may attenuate early murine MI injury; hypothesis-generating for macrophage-targeted therapies, should not yet change practice.
OBJECTIVES: To study the effects of myeloid-specific knockout of SHP2 on early myocardial infarction and explore its molecular mechanism. METHODS: The model of myocardial infarction was established by using SHP2 in myeloid-specific knockout mice, and the effect of SHP2MAC-KO on myocardial function was detected by echocardiography. The effects of SHP2 on myocardial infarct size in myeloid-specific knockout mice was examined by TTC assay and Masson staining. Then, the detection of apoptosis was performed using TUNEL staining and inflammatory cell infiltration was observed using immunohistochemical staining. Moreover, macrophages in mouse hearts were selected by Flow Cytometry and treated with PI3K inhibitors respectively. Western blotting was then used to detect protein expression of p-SHP2 and PI3K/PLCγ signaling pathway. The phagocytic ability of cells was detected by endocytosis test, and the expression of inflammatory cytokines was detected by ELISA. RESULTS: Specific knockout of SHP2 in mice with myocardial infarction can improve the cardiac function, decrease infarct size, and reduce apoptosis as well as inflammatory cell infiltration. It also can mediate the PI3K/PLCγ signaling pathway in macrophages, which in turn enhances the endocytosis of macrophages and reduces the expression of inflammatory cytokines in macrophages. CONCLUSIONS: Myeloid-specific knockout of SHP2 regulates PI3K/PLCγ signaling pathway to protect against early myocardial infarction injury.
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Sha et al. (2023) studied Early myocardial infarction injury. Myeloid-specific knockout of SHP2 vs. Wild-type mice was evaluated on Cardiac function (EF, FS, LVID, LVAW) and myocardial infarct size (p=<0.01). Myeloid-specific knockout of SHP2 significantly improved cardiac function, decreased infarct size, and reduced apoptosis and inflammatory cell infiltration in mice with myocardial infarction.
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