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Higher matrix stiffness promotes VSMC senescence by affecting mitochondria-ER contact sites and mitochondria/ER dysfunction.
He, Haipeng; Zeng, Baozhu; Wu, Xinxiang; Hou, Jianfeng; Wang, Yannan; Wang, Yanheng; Lin, Yuqing; Wu, Peng; Zheng, Changyu; Yin, Henghui; Wang, Nan.
Afiliación
  • He H; Department of Vascular Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
  • Zeng B; Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China.
  • Wu X; Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China.
  • Hou J; Department of Joint and Trauma Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
  • Wang Y; School of Medicine, Shenzhen Campus of Sun Yat-sen University, Sun Yat-Sen University, Shenzhen, China.
  • Wang Y; Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
  • Lin Y; School of Medicine, Shenzhen Campus of Sun Yat-sen University, Sun Yat-Sen University, Shenzhen, China.
  • Wu P; School of Medicine, Shenzhen Campus of Sun Yat-sen University, Sun Yat-Sen University, Shenzhen, China.
  • Zheng C; School of Medicine, Shenzhen Campus of Sun Yat-sen University, Sun Yat-Sen University, Shenzhen, China.
  • Yin H; Department of Vascular Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
  • Wang N; Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China.
FASEB J ; 37(12): e23318, 2023 12.
Article en En | MEDLINE | ID: mdl-37997545
Abdominal aortic aneurysm (AAA) is a prevalent condition characterized by the weakening and bulging of the abdominal aorta. This study aimed to investigate the impact of a stiff matrix on vascular smooth muscle cells (VSMCs) in AAA development. Bioinformatics analysis revealed that differentially expressed genes (DEGs) in VSMCs of an AAA mouse model were enriched in cellular senescence and related pathways. To simulate aging-related changes, VSMCs were cultured on stiff matrices, and compared to those on soft matrices, the VSMCs cultured on stiff matrices exhibited cellular senescence. Furthermore, the mutual distance between mitochondria and endoplasmic reticulum (ER) in VSMCs was increased, indicating altered mitochondria-endoplasmic reticulum contacts (MERCs). The observed upregulation of reactive oxygen species (ROS) levels, antioxidant gene expression, and decreased mitochondrial membrane potential suggested the presence of mitochondrial dysfunction in VSMCs cultured on a stiff matrix. Additionally, the induction of ER stress-related genes indicated ER dysfunction. These findings collectively indicated impaired functionality of both mitochondria and ER in VSMCs cultured on a stiff matrix. Moreover, our data revealed that high lipid levels exacerbated the effects of high matrix stiffness on VSMCs senescence, MERC sites, and mitochondria/ER dysfunction. Importantly, treatment with the antilipemic agent CI-981 effectively reversed these detrimental effects. These findings provide insights into the role of matrix stiffness, mitochondrial dysfunction, ER stress, and lipid metabolism in AAA development, suggesting potential therapeutic targets for intervention.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Aneurisma de la Aorta Abdominal / Músculo Liso Vascular Límite: Animals Idioma: En Revista: FASEB J Asunto de la revista: BIOLOGIA / FISIOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Aneurisma de la Aorta Abdominal / Músculo Liso Vascular Límite: Animals Idioma: En Revista: FASEB J Asunto de la revista: BIOLOGIA / FISIOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos