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Biochem Biophys Res Commun. 2018 Oct 20;505(1):282-289. doi: 10.1016/j.bbrc.2018.09.002. Epub 2018 Sep 20.

Alleviation of A disintegrin and metalloprotease 10 (ADAM10) on thromboangiitis obliterans involves the HMGB1/RAGE/ NF-κB pathway.

Author information

1
Department of Vascular Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, 250021, China; Department of Vascular Surgery, The People's Hospital of Anqiu, Anqiu, Shandong, 262100, China.
2
Department of Vascular Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, 250021, China.
3
Department of Vascular Surgery, The People's Hospital of Anqiu, Anqiu, Shandong, 262100, China.
4
Department of Vascular Surgery, Shanxian Central Hospital of Shandong, Heze, Shandong, 274399, China.
5
Department of Vascular Surgery, Jining First People's Hospital, Jining, Shandong, 272011, China.
6
Department of Vascular Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, 250021, China. Electronic address: jinxingx1986@163.com.
7
Department of Vascular Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, 250021, China. Electronic address: yhdoctor@163.com.

Abstract

Thromboangiitis obliterans (TAO), also known as Buerger's disease, is a nonatherosclerotic inflammatory disease that influences medium- and small-sized blood vessels of extremities. However, mechanisms underlying TAO are still unclear. As a mediator associated with inflammation, A disintegrin and metalloprotease 10 (ADAM10) was hypothesized to play inhibitory roles in the development of TAO. Thus, the objective of this study is to investigate the effects of ADAM10 in a sodium laurate-induced TAO rat model and elucidate underlying mechanisms. Male Wistar rats were randomly divided into four groups (n = 6) for treatment: sham-operated (SHAM), TAO model (TAO), ADAM10 low dose injection (3 mg/kg; ADAM10-LD) and ADAM10 high dose injection (6 mg/kg; ADAM10-HD). After 14-day treatment, color Doppler ultrasound and hematology analysis indicated TAO rats displayed higher whole blood viscosity and blood platelet count compared with those in the SHAM group. Histologic evaluation and transmission electron microscopy revealed that the ultrastructural damages of vascular smooth muscle and endothelial cells were observed in TAO rats, such as fractured endoplasmic reticulum, decreased cell counts, and fibrillation. On the other hand, the typical signs and symptoms of TAO rats were significantly alleviated via ADAM10 treatment with a dose-dependent pattern. Real-time PCR and western blot results revealed that the expression of high-mobility-group box 1 (HMGB1), receptor for advanced glycation end-products (RAGE) and nuclear factor-kappa B (NF-κB) increased in TAO rats whereas decreased by ADAM10 treatment in both mRNA and protein levels. In conclusion, the results suggest ADAM10 alleviates symptoms of sodium laurate-induced TAO in rats via the RAGE/NF-κB signaling pathway and provides insight into the molecular basis and a potential therapeutic strategy for TAO.

KEYWORDS:

ADAM10; HMGB1; NF-κB; RAGE; Thromboangiitis obliterans

PMID:
30245136
DOI:
10.1016/j.bbrc.2018.09.002
[Indexed for MEDLINE]

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