Liu Danan, Mo Xiangang, Zhang Hongming, Wu Lirong, Tan Juan, Xiao Jincui, Qin Zheng
Department of Cardiology, The Affiliated Hospital of Guizhou Medical University Guiyang, P. R. China.
Institute of Medical Sciences, Guizhou Medical University Guiyang, P. R. China.
Int J Clin Exp Pathol. 2018 May 1;11(5):2479-2487. eCollection 2018.
Percutaneous coronary intervention (PCI) is used commonly for coronary artery disease (CAD); however, restenosis is a proliferative response and frequent sequela to this treatment. Although the introduction of drug-eluting stents has convincingly reduced the incidence of vascular restenosis, restenosis remains a problem. The present study was designed to investigate the effects of the heme oxygenase-1 (HO-1) on restenosis formation after balloon injury in a rabbit carotid artery model. We found that involvement of the HO-1 in defensive restenosis formation was independent of the levels of blood lipid. Activation of HO-1 induced by chlorhematin treatment alleviated vascular restenosis after balloon injury in a rabbit carotid artery model, whereas inhibition of HO-1 by zinc protoporphyrin treatment exacerbated restenosis formation. Furthermore, overexpression of HO-1 inhibited nuclear factor kappa B subunit 1 (NF-кB) activity and decreased tumor necrosis factor-alpha (TNF-α) and endothelin 1 (ET-1) expression. In conclusion, our study provides preliminary data suggesting that HO-1 alleviates vascular restenosis after balloon injury in a rabbit carotid artery model by inhibiting NF-кB, TNF-α and ET-1 expression, indicating induction of HO-1 activation may be a feasible therapeutic target for treating vessels resistant to restenosis.
经皮冠状动脉介入治疗（PCI）常用于治疗冠状动脉疾病（CAD）；然而，再狭窄是这种治疗常见的增殖性反应和后遗症。尽管药物洗脱支架的引入显著降低了血管再狭窄的发生率，但再狭窄仍然是一个问题。本研究旨在探讨血红素加氧酶-1（HO-1）在兔颈动脉球囊损伤后再狭窄形成中的作用。我们发现，HO-1参与防御性再狭窄形成与血脂水平无关。氯化血红素处理诱导的HO-1激活减轻了兔颈动脉球囊损伤后的血管再狭窄，而锌原卟啉处理抑制HO-1则加剧了再狭窄的形成。此外，HO-1的过表达抑制了核因子κB亚基1（NF-κB）的活性，并降低了肿瘤坏死因子-α（TNF-α）和内皮素1（ET-1）的表达。总之，我们的研究提供了初步数据，表明HO-1通过抑制NF-κB、TNF-α和ET-1的表达减轻兔颈动脉球囊损伤后的血管再狭窄，提示诱导HO-1激活可能是治疗难治性再狭窄血管的一个可行治疗靶点。
