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Adipose-Derived Stem Cell Transplantation Inhibits Vascular Inflammatory Responses and Endothelial Dysfunction in Rats with Atherosclerosis

Yonsei Medical Journal 2019년 60권 11호 p.1036 ~ 1044
 ( Fan Mingqiang ) - Pingliang People’s Hospital Department of Dardiovascular

 ( Bai Jing ) - Pingliang People’s Hospital Department of Dardiovascular
 ( Ding Tao ) - Pingliang People’s Hospital Department of Dardiovascular
 ( Yang Xiangxiang ) - Pingliang People’s Hospital Department of Dardiovascular
 ( Si Qiaoke ) - Pingliang People’s Hospital Department of Dardiovascular
 ( Nie Dengmei ) - Second Provincial People’s Hospital Department of Pathology

Abstract


Purpose: This study aimed to investigate the effect of adipose-derived stem cell (ADSC) transplantation on atherosclerosis (AS) and its underlying mechanisms.

Materials and Methods: In our study, rat AS model was established, and ADSCs were isolated and cultured. Atherosclerotic plaque and pathological symptoms of thoracic aorta were measured by Oil Red O staining and Hematoxylin-Eosin staining, respectively. Total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were measured by an automatic biochemical analyzer. Expressions of vascular endothelial growth factor (VEGF), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), aortic endothelin-1 (ET-1), interleukin-6 (IL-6), c-reactive protein (CRP), and tumor necrosis factor α (TNF-α) were measured by enzyme linked immunosorbent assay, VEGF, VCAM-1, ICAM-1, ET-1, respectively, and NF-κB p65 mRNA expressions were detected by quantitative real-time polymerase chain reaction. Protein expressions of VEGF, VCAM-1, ICAM-1, ET-1, NF-κB p65, p-NF-κB p65, and IκBα were measured by western blot. Moreover, NF-κB p65 expression was measured by immunofluorescence staining.

Results: ADSC transplantation alleviated the pathological symptoms of aortic AS. ADSC transplantation decreased the levels of TC, TG, and LDL-C and increased serum HDL-C level. Meanwhile, ADSC transplantation decreased the levels of IL-6, CRP, and TNF-α in AS rats. Moreover, the expressions of VEGF, ET-1, VCAM-1, and ICAM-1 were decreased by ADSC transplantation. ADSC transplantation inhibited phosphorylation of NF-κB p65 and promoted IκBα expression in AS rats.

Conclusion: Our study demonstrated that ADSC transplantation could inhibit vascular inflammatory responses and endothelial dysfunction by suppressing NF-κB pathway in AS rats.

키워드

ADSC; atherosclerosis; endothelial dysfunction; inflammatory responses; NF-κB pathway
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