HnRNPA1 Prevents Endothelial-to-mesenchymal Transition-induced VSMC Activation and Neointimal Hyperplasia in Vein Grafts.

Liu, Haoliang; Wang, Chaoqun; Wang, Rui; Zhang, Yi; Jian, Bohao; Zhou, Zhuoming; Wu, Zhongkai; Liang, Mengya

Liu, Haoliang; Wang, Chaoqun; Wang, Rui; Zhang, Yi; Jian, Bohao; Zhou, Zhuoming; Wu, Zhongkai; Liang, Mengya.

Afiliación

Liu H; Department of Cardiac Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, Guangdong, China.
Wang C; Department of Cardiac Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, Guangdong, China.
Wang R; Department of Cardiology, Guangzhou Hospital of Integrated Traditional and West Medicine, Guangzhou, 510080, Guangdong, China.
Zhang Y; Department of Cardiac Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, Guangdong, China.
Jian B; Department of Cardiac Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, Guangdong, China.
Zhou Z; Department of Cardiac Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, Guangdong, China.
Wu Z; Department of Cardiac Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, Guangdong, China. wuzhk@mail.sysu.edu.cn.
Liang M; Department of Cardiac Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, Guangdong, China. liangmya@mail.sysu.edu.cn.

J Cardiovasc Transl Res ; 2024 Jul 24.

Article en En | MEDLINE | ID: mdl-39046653

ABSTRACT

ABSTRACT

Endothelial-to-mesenchymal transition (EndoMT) is associated with neointimal hyperplasia and vein graft failure, and heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) has emerged as a major modulator of EMT. We aimed to investigate the functional consequence of EndoMT in neointimal hyperplasia and the precise role of hnRNPA1 in the regulation of EndoMT and neointimal hyperplasia. We investigated the spatial and temporal distribution characteristics of EndoMT cells in a mouse model of vein graft transplantation. In vitro, we studied the interaction between EndoMT cells and VSMCs, and the underlying mechanism was investigated by cytokine antibody assays. In cultured HUVECs, we studied the effect of hnRNPA1 on EndoMT and the cellular interactions by using siRNA-mediated knockdown and adenovirus-mediated overexpression. We further investigated the role of hnRNPA1 in EndoMT and neointimal hyperplasia in vivo with an AAV-mediated EC-specific hnRNPA1 overexpression murine model. We demonstrated the presence of EndoMT cells during the initial stage of neointimal formation, and that EndoMT cells promoted the proliferation and migration of VSMCs in vitro. Mechanistic studies revealed that EndoMT cells express and secrete a higher level of PDGF-B. Furthermore, we found a regulatory role for hnRNPA1 in EndoMT in vitro and in vivo. Similarly, we found that hnRNPA1 overexpression in ECs reduced the expression and secretion of PDGF-B during EndoMT, effectively inhibiting EndoMT cell-mediated activation of VSMCs in vitro and neointimal formation in vivo. Taken together, these findings indicate that EndoMT cells can activate VSMCs through a paracrine mechanism mediated by hnRNPA1 and lead to neointimal hyperplasia.

Palabras clave

Cellular interaction; Endothelial-to-mesenchymal transition; Neointimal hyperplasia; Vein graft failure; hnRNPs

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Cardiovasc Transl Res Asunto de la revista: ANGIOLOGIA / CARDIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos

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