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Development of a PCSK9-targeted nanoparticle vaccine to effectively decrease the hypercholesterolemia.
Fang, Qiannan; Lu, Xinyu; Zhu, Yuanqiang; Lv, Xi; Yu, Fei; Ma, Xiancai; Liu, Bingfeng; Zhang, Hui.
Afiliação
  • Fang Q; Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China; Medical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, G
  • Lu X; Medical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510080, China.
  • Zhu Y; Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University·Zhaoqing Hospital, Zhaoqing, Guangdong 510630, China.
  • Lv X; Medical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510080, China.
  • Yu F; Medical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510080, China.
  • Ma X; Guangzhou National Laboratory, Guangzhou International Bio-Island, Guangzhou, Guangdong 510005, China.
  • Liu B; Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
  • Zhang H; Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China. Electronic address: zhangh92@ma
Cell Rep Med ; 5(6): 101614, 2024 Jun 18.
Article em En | MEDLINE | ID: mdl-38897173
ABSTRACT
Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low-density lipoprotein receptor (LDLR) and mediates its internalization and degradation, resulting in an increase in LDL cholesterol levels. Recently, PCSK9 emerged as a therapeutic target for hypercholesterolemia and atherosclerosis. In this study, we develop a PCSK9 nanoparticle (NP) vaccine by covalently conjugating the catalytic domain (aa 153-aa 454, D374Y) of PCSK9 to self-assembled 24-mer ferritin NPs. We demonstrate that the PCSK9 NP vaccine effectively induces interfering antibodies against PCSK9 and reduces serum lipids levels in both a high-fat diet-induced hypercholesterolemia model and an adeno-associated virus-hPCSK9D374Y-induced hypercholesterolemia model. Additionally, the vaccine significantly reduces plaque lesion areas in the aorta and macrophages infiltration in an atherosclerosis mouse model. Furthermore, we discover that the vaccine's efficacy relied on T follicular help cells and LDLR. Overall, these findings suggest that the PCSK9 NP vaccine holds promise as an effective treatment for hypercholesterolemia and atherosclerosis.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Receptores de LDL / Vacinas / Modelos Animais de Doenças / Aterosclerose / Nanopartículas / Pró-Proteína Convertase 9 / Hipercolesterolemia Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Receptores de LDL / Vacinas / Modelos Animais de Doenças / Aterosclerose / Nanopartículas / Pró-Proteína Convertase 9 / Hipercolesterolemia Idioma: En Ano de publicação: 2024 Tipo de documento: Article