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Atorvastatin-induced tolerogenic dendritic cells improve cardiac remodeling by suppressing TLR-4/NF-κB activation after myocardial infarction.
Wang, Qian; Chen, Zhaoyang; Guo, Junjie; Peng, Xiaoping; Zheng, Zeqi; Chen, Hang; Liu, Haibo; Ma, Yuanji; Zhu, Jianbing.
Afiliação
  • Wang Q; Department of Blood Transfusion, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, People's Republic of China.
  • Chen Z; Heart Center of Fujian Province, Union Hospital, Fujian Medical University, 29 Xin-Quan Road, Fuzhou, 350001, People's Republic of China.
  • Guo J; Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People's Republic of China.
  • Peng X; Qingdao Municipal Key Laboratory of Hypertension, Qingdao, Shandong, People's Republic of China.
  • Zheng Z; Department of Cardiology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, People's Republic of China.
  • Chen H; Jiangxi Hypertension Research Institute, Nanchang, People's Republic of China.
  • Liu H; Department of Cardiology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, People's Republic of China.
  • Ma Y; Jiangxi Hypertension Research Institute, Nanchang, People's Republic of China.
  • Zhu J; Heart Center of Fujian Province, Union Hospital, Fujian Medical University, 29 Xin-Quan Road, Fuzhou, 350001, People's Republic of China.
Inflamm Res ; 72(1): 13-25, 2023 Jan.
Article em En | MEDLINE | ID: mdl-36315279
ABSTRACT

OBJECTIVE:

Myocardial infarction (MI) caused by ischemic cardiomyocyte necrosis induces inflammatory responses that strongly affect ventricular remodeling. Tolerogenic dendritic cells (tDCs) can suppress this effect on inflammatory responses. However, the precise role of atorvastatin-induced tDCs in ventricular remodeling after MI remains unclear.

METHODS:

To explore the effect of necrotic cardiomyocytes (SNC) and/or atorvastatin on DC function, the expression of CD40, CD80, CD86, and MHC-II was determined using flow cytometry. The protein levels of TLR-4/NF-κB-related molecules were evaluated using western blotting. The infarct area after MI was determined via 2,3,5-triphenyltetrazolium chloride staining. The TUNEL assay was employed to evaluate the apoptosis of cardiomyocytes in heart sections. Masson's trichrome method was used to determine the extent of fibrosis.

RESULTS:

Compared to the DCs co-cultured with PBS (control), cells co-cultured with Supernatant-IM or Supernatant-NH produced higher levels of inflammatory cytokines, including TNF-α, IL-1, IL-6, IL-12P40, and IL-8. This cytokine production was impaired by atorvastatin treatment. SNC treatment induced DC maturation and enhanced inflammatory cytokine secretion and oxidative stress through TLR-4/NF-κB pathway activation. Compared to that in the PBS-treated group, the left ventricular ejection fraction was significantly improved after tDC treatment. Additionally, compared to that in the PBS-treated group, tDC treatment reduced the left ventricular end-diastolic and end-systolic diameters in mice. Furthermore, treatment with tDCs improved the left ventricular systolic function, attenuated inflammatory cell infiltration, and reduced cardiomyocyte apoptosis, myocardial fibrosis, and infarct size compared to those in the control group.

CONCLUSIONS:

Adoptive transfer of atorvastatin-induced tDCs alleviated post-infarction cardiomyocyte apoptosis and myocardial fibrosis in association with decreased inflammatory cell infiltration and inhibited oxidative stress, likely by suppressing TLR-4/NF-κB activation after myocardial infarction.
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: NF-kappa B / Infarto do Miocárdio Limite: Animals Idioma: En Revista: Inflamm Res Assunto da revista: ALERGIA E IMUNOLOGIA / PATOLOGIA Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: NF-kappa B / Infarto do Miocárdio Limite: Animals Idioma: En Revista: Inflamm Res Assunto da revista: ALERGIA E IMUNOLOGIA / PATOLOGIA Ano de publicação: 2023 Tipo de documento: Article