Exacerbation of atherosclerosis by STX17 knockdown: Unravelling the role of autophagy and inflammation.

Cui, Xinyue; Wang, Bo; Han, Dongjian; Cheng, Mengdie; Yuan, Peiyu; Du, Pengchong; Hou, Yachen; Su, Chang; Tang, Junnan; Zhang, Jinying

Cui, Xinyue; Wang, Bo; Han, Dongjian; Cheng, Mengdie; Yuan, Peiyu; Du, Pengchong; Hou, Yachen; Su, Chang; Tang, Junnan; Zhang, Jinying.

Afiliación

Cui X; Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Wang B; Key Laboratory of Cardiac Injury and Repair of Henan Province, Zhengzhou, Henan, China.
Han D; Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Cheng M; Key Laboratory of Cardiac Injury and Repair of Henan Province, Zhengzhou, Henan, China.
Yuan P; Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Du P; Key Laboratory of Cardiac Injury and Repair of Henan Province, Zhengzhou, Henan, China.
Hou Y; Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Su C; Key Laboratory of Cardiac Injury and Repair of Henan Province, Zhengzhou, Henan, China.
Tang J; Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Zhang J; Key Laboratory of Cardiac Injury and Repair of Henan Province, Zhengzhou, Henan, China.

J Cell Mol Med ; 28(10): e18402, 2024 May.

Article en En | MEDLINE | ID: mdl-39008328

ABSTRACT

ABSTRACT

Syntaxin 17 (STX17) has been identified as a crucial factor in mediating the fusion of autophagosomes and lysosomes. However, its specific involvement in the context of atherosclerosis (AS) remains unclear. This study sought to elucidate the role and mechanistic contributions of STX17 in the initiation and progression of AS. Utilizing both in vivo and in vitro AS model systems, we employed ApoE knockout (KO) mice subjected to a high-fat diet and human umbilical vein endothelial cells (HUVECs) treated with oxidized low-density lipoprotein (ox-LDL) to assess STX17 expression. To investigate underlying mechanisms, we employed shRNA-STX17 lentivirus to knock down STX17 expression, followed by evaluating autophagy and inflammation in HUVECs. In both in vivo and in vitro AS models, STX17 expression was significantly upregulated. Knockdown of STX17 exacerbated HUVEC damage, both with and without ox-LDL treatment. Additionally, we observed that STX17 knockdown impaired autophagosome degradation, impeded autophagy flux and also resulted in the accumulation of dysfunctional lysosomes in HUVECs. Moreover, STX17 knockdown intensified the inflammatory response following ox-LDL treatment in HUVECs. Further mechanistic exploration revealed an association between STX17 and STING; reducing STX17 expression increased STING levels. Further knockdown of STING enhanced autophagy flux. In summary, our findings suggest that STX17 knockdown worsens AS by impeding autophagy flux and amplifying the inflammatory response. Additionally, the interaction between STX17 and STING may play a crucial role in STX17-mediated autophagy.

Asunto(s)

Aterosclerosis; Autofagia; Células Endoteliales de la Vena Umbilical Humana; Inflamación; Lipoproteínas LDL; Proteínas Qa-SNARE; Autofagia/genética; Animales; Humanos; Aterosclerosis/metabolismo; Aterosclerosis/genética; Aterosclerosis/patología; Células Endoteliales de la Vena Umbilical Humana/metabolismo; Inflamación/metabolismo; Inflamación/patología; Inflamación/genética; Proteínas Qa-SNARE/metabolismo; Proteínas Qa-SNARE/genética; Ratones; Lipoproteínas LDL/metabolismo; Técnicas de Silenciamiento del Gen; Lisosomas/metabolismo; Ratones Noqueados; Masculino; Ratones Endogámicos C57BL; Modelos Animales de Enfermedad; Dieta Alta en Grasa/efectos adversos; Apolipoproteínas E/genética; Apolipoproteínas E/metabolismo; Apolipoproteínas E/deficiencia

Palabras clave

STING; atherosclerosis; autophagy; inflammation; syntaxin 17

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autofagia / Aterosclerosis / Proteínas Qa-SNARE / Células Endoteliales de la Vena Umbilical Humana / Inflamación / Lipoproteínas LDL Límite: Animals / Humans / Male Idioma: En Revista: J Cell Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido

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