Adiponectin Prevents Restenosis Through Inhibiting Cell Proliferation in a Rat Vein Graft Model

Zhou, Yang; Dai, Chun; Zhang, Bing; Ge, Jianjun

doi:10.36660/abc.20200761

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Original Article • Arq. Bras. Cardiol. 117 (6) • Dec 2021 • https://doi.org/10.36660/abc.20200761 linkcopy

Adiponectin Prevents Restenosis Through Inhibiting Cell Proliferation in a Rat Vein Graft Model

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Background: Coronary artery bypass grafting (CABG) continues to be an effective therapy for coronary artery disease patients, but the vein graft is prone to restenosis or occlude. Adiponectin (ADP) is a plasma hormone protein with the function of regulating cell proliferation.

Objective: This study used two different doses of ADP protein in a rat vein graft model to stimulate vein graft change. The aim of our study was to investigate the effect of ADP on vein graft restenosis.

Methods: Autologous jugular veins were implanted as carotid interposition grafts through the anastomotic cuff technique in Sprague Dawley rats. Adiponectin (2.5 μg and 7.5 μg) was delivered to the vein bypass grafts in a perivascular fashion, suspended in a 30% Pluronic-F127 gel. No treatment (bypass only) and vehicle loaded Pluronic gel served as controls. Comparisons were made with one-way analysis of variance and a post-hoc test, with p < 0.05 considered significant.

Results: Cell proliferation (PCNA index) was significantly low in adiponectin-treated versus control and vehicle-gel-treated grafts, both in intima and adventitia, as of day 3 (p < 0.01). VCAM-1 and ICAM-1 evaluated by immunohistochemistry significantly down-regulated in the adiponectin-treated vein grafts in the fourth week (p <0.01). Treatment of vein grafts with adiponectin-loaded gels reduced intimal, media, and adventitia thickness when compared with the control and vehicle-gel-treated vein grafts at day 28 (p < 0.01).

Conclusions: Our studies provide further support for the potential therapeutic role of adiponectin in modulating vascular injury and repair.

Keywords: Adiponectin; Cell Proliferation; Hyperplasia

Groups	Time(day)	Control N=6	Vehicle gel N=6	L-ADP N=6	H-ADP N=6	Analysis
Intima thickness (μm)	3	25.47±1.02	25.10±1.53	26.55±1.05	26.46±0.71	ANOVA
	14	111.69±5.31	106.62±5.57	75.12±4.94^ p < 0.01 versus control group. ^# # p < 0.05 versus vehicle gel group, #	75.46±3.59^ p < 0.01 versus control group. ^## ## p < 0.01 versus vehicle gel group.	ANOVA
	28	196.09±6.78	190.44±7.68	128.30±6.01^ p < 0.01 versus control group. ^## ## p < 0.01 versus vehicle gel group.	96.96±5.45^ p < 0.01 versus control group. ^## ## p < 0.01 versus vehicle gel group.	ANOVA
Media thickness (μm)	3	94.00±4.19	95.47±3.38	76.93±5.30^ p < 0.01 versus control group. ^# # p < 0.05 versus vehicle gel group, #	69.03±5.94^ p < 0.01 versus control group. ^# # p < 0.05 versus vehicle gel group, #	ANOVA
	14	107.19±3.66	107.41±5.48	93.86±3.17^ p < 0.01 versus control group. ^## ## p < 0.01 versus vehicle gel group.	82.83±4.13^ p < 0.01 versus control group. ^## ## p < 0.01 versus vehicle gel group.	ANOVA
	28	158.83±8.39	157.75±8.75	109.67±7.16^ p < 0.01 versus control group. ^# # p < 0.05 versus vehicle gel group, #	104.02±7.12^ p < 0.01 versus control group. ^# # p < 0.05 versus vehicle gel group, #	ANOVA
Adventitia thickness (μm)	3	56.09±3.42	53.03±4.59	54.51±3.95	59.21±4.28	ANOVA
	14	112.03±7.08	111.87±6.35	85.04±6.35^ p < 0.01 versus control group. ^## ## p < 0.01 versus vehicle gel group.	86.52±5.20^ p < 0.01 versus control group. ^## ## p < 0.01 versus vehicle gel group.	ANOVA
	28	152.31±3.55	154.49±6.55	95.70±6.05^ p < 0.01 versus control group. ^## ## p < 0.01 versus vehicle gel group.	90.15±4.87^ p < 0.01 versus control group. ^## ## p < 0.01 versus vehicle gel group.	ANOVA

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Sociedade Brasileira de Cardiologia - SBC Avenida Marechal Câmara, 160, sala: 330, Centro, CEP: 20020-907, (21) 3478-2700 - Rio de Janeiro - RJ - Brazil, Fax: +55 21 3478-2770 - São Paulo - SP - Brazil
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[TFN6] The values of thickness are presented as mean ± SD (N=6).

[TFN7] ^*
p < 0.05 versus control group,

[TFN8] ^**
p < 0.01 versus control group.

[TFN9] ^#
p < 0.05 versus vehicle gel group,

[TFN10] ^##
p < 0.01 versus vehicle gel group.