Targeting proprotein convertase subtilisin/kexin type 7 in macrophages as a therapeutic strategy to mitigate myocardial infarction-induced inflammation
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Myocardial infarction (MI), a major form of coronary arterydisease (CAD), triggers a severe inflammatory response in theheart, resulting in increased cell death and adverse ventricularremodeling. Despite treatment advancements, MI remains asignificant risk factor for heart failure, underscoring the necessityfor a more in-depth exploration of immune cell mechanisms. Proprotein convertase subtilisin/kexin type 7 (PCSK7),expressed in various tissues and immune cells, has been implicatedin cardiovascular disease, yet its specific role incardiac immune cells remains poorly understood. This studyaimed to elucidate the role of PCSK7 in MI-related inflammation. Our findings indicate that PCSK7 deficiency reducescirculating cholesterol levels, potentially mitigating infarctinjury and improving cardiac function by modulating immunecells. Additionally, PCSK7 promotes macrophage activationand lipid uptake at the ischemic site, intensifying the pathology. We also observed that PCSK7 activates the TNF-/JNKsignaling pathway in macrophages intracellularly, amplifyingthe inflammatory response. Therefore, targeting PCSK7 in macrophagescould help mitigate post-MI inflammation, alleviatedisease severity, and offer novel therapeutic strategies forpatients with CAD.
Abstract
Myocardial infarction (MI), a major form of coronary arterydisease (CAD), triggers a severe inflammatory response in theheart, resulting in increased cell death and adverse ventricularremodeling. Despite treatment advancements, MI remains asignificant risk factor for heart failure, underscoring the necessityfor a more in-depth exploration of immune cell mechanisms. Proprotein convertase subtilisin/kexin type 7 (PCSK7),expressed in various tissues and immune cells, has been implicatedin cardiovascular disease, yet its specific role incardiac immune cells remains poorly understood. This studyaimed to elucidate the role of PCSK7 in MI-related inflammation. Our findings indicate that PCSK7 deficiency reducescirculating cholesterol levels, potentially mitigating infarctinjury and improving cardiac function by modulating immunecells. Additionally, PCSK7 promotes macrophage activationand lipid uptake at the ischemic site, intensifying the pathology. We also observed that PCSK7 activates the TNF-/JNKsignaling pathway in macrophages intracellularly, amplifyingthe inflammatory response. Therefore, targeting PCSK7 in macrophagescould help mitigate post-MI inflammation, alleviatedisease severity, and offer novel therapeutic strategies forpatients with CAD.
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