| چکیده انگلیسی مقاله |
Objective
C1q/TNF-related proteins 1 (CTRP1) is a recently identified adiponectin associated with obesity-linked disorders and adverse cardiovascular events. The effect of CTRP1 on cardiac fibrosis has not yet been fully elucidated; thus, we aimed to explore this association.
Materials and Methods
In this experimental study, a mouse model of cardiac fibrosis was established by administering
isoproterenol (ISO) (subcutaneously injecting 10 mg/kg/day for 3 days and then 5 mg/kg/day for 11 days). Mice were also injected with recombinant CTRP1 protein (200 μg/kg) 14 days after the final ISO administration. Adult mouse fibroblasts were isolated and stimulated with transforming growth factor (TGF) β1, followed by treatment with recombinant CTRP1. Primary bone marrow-derived macrophages were isolated from C57BL/6J mice and treated with recombinant CTRP1 as well.
Results
CTRP1 level was increased in mouse plasma and heart tissue 2 weeks after ISO injection. Our findings
indicated that recombinant CTRP1 injection aggravated ISO-induced cardiac fibrosis and dysfunction. However,
recombinant CTRP1 did not alter TGFβ1-induced fibroblast proliferation and activation or collagen transcription.
Recombinant CTRP1 exacerbated ISO-induced macrophage infiltration and inflammatory response. We determined
that macrophages treated with recombinant CTRP1 showed increased pro-inflammatory cytokine release. Fibroblasts
co-cultured with macrophages treated with recombinant CTRP1 showed increased proliferation and collagen
transcription. We also found that CTRP1 upregulated the NADPH oxidase 2 (NOX2)/p38 pathway in macrophages.
When we inhibited p38 signaling, the pro-inflammatory effect of CTRP1 on macrophages was counteracted. Fibroblasts
co-cultured with macrophages treated with a p38 inhibitor also showed limited proliferation and collagen transcription.
Conclusion: Cardiac fibrosis was aggravated with the activation of the NOX2/p38 pathway in macrophages after
CTRP1 treatment. |
| نویسندگان مقاله |
Chenyu Li |
Department of Cardiology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei,
P.R. China
Shaozhen Ying |
Department of Cardiology, Jiangxi provincial People’s Hospital, Affiliated to Nanchang University, Nanchang, Jiangxi, China
Xiaolin Wu |
Department of Cardiology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei,
P.R. China
Tongjian Zhu |
Department of Cardiology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei,
P.R. China
Qing Zhou |
Department of Cardiology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei,
P.R. China
Yue Zhang |
Department of Cardiology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei,
P.R. China
Yongsheng Liu |
Department of Cardiology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei,
P.R. China
Rui Zhu |
Department of Cardiology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei,
P.R. China
Negar Karimi Hajishoreh |
Tissue Engineering and Applied Cell Sciences Division, Department of Anatomical Sciences, Faculty of Medical Sciences, Tarbiat
Modares University, Tehran, Iran
|