A new RXR agonist, HX630, suppresses intimal hyperplasia in a mouse blood flow cessation model
A new RXR agonist, HX630, suppresses intimal hyperplasia in a mouse blood flow cessation model
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DOI：
10.1016/j.yjmcc.2006.07.022
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发表时间：
2006-11-01
影响因子：
5
通讯作者：
Isobe, Mitsuaki
中科院分区：
文献类型：
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作者：
Haraguchi, Go;Suzuki, Jun-ichi;Isobe, Mitsuaki
核受体类视黄醇X受体（RXR）与其他核受体形成异源二聚体并发挥抗炎作用。RXR与动脉硬化的进展有关；然而，选择性激活RXR对平滑肌细胞（SMC）增殖的影响尚不清楚。我们合成了一种新的RXR激动剂HX630，并研究了其对血管SMC （VSMC）增殖的影响。雄性C57BL/6小鼠（n = 15）结扎左颈动脉后，连续4周给予HX630 5或10 mg/kg/d。饲喂hx630的小鼠与对照组相比，内膜增生的进展明显受到抑制（内膜比为0.286 +/- 0.093∶1.022 +/- 0.134,P < 0.05）。颈动脉免疫组化结果显示，HX630对内膜增厚病变的细胞因子和粘附分子染色有抑制作用。HX630可抑制IL -1 β诱导的VSMC增殖，抑制VSMC中IL-6 mRNA和蛋白的表达。RXR激动剂HX630对VSMCs具有体内外抗增殖作用。因此，RXR可作为血管损伤和内膜增厚的治疗靶点。(c) 2006爱思唯尔公司版权所有。
The nuclear receptor retinoid X receptor (RXR) forms heterodimers with other nuclear receptors and exerts anti-inflamminatory effects. RXR is implicated in the progression of arteriosclerosis; however, the effects of selective RXR activation on smooth muscle cell (SMC) proliferation are unknown. We synthesized a novel RXR agonist, HX630, and examined its effect on vascular SMC (VSMC) proliferation. Male C57BL/6 mice (n = 15) were subjected to ligation of the left carotid artery and fed 5 or 10 mg/kg/day HX630 for 4 weeks. HX630-fed mice showed significantly suppressed intimal hyperplasia progression compared to that in control mice (0.286 +/- 0.093 vs. 1.022 +/- 0.134 intimahnedia ratio, P < 0.05). Immunohistochemistry of the carotid artery showed that HX630 suppressed cytokine and adhesion molecule staining in lesions undergoing intimal thickening. Interleukin (IL)-1 beta-induced VSMC proliferation was inhibited by HX630 and the expression of IL-6 mRNA and protein in VSMCs was suppressed. The RXR agonist HX630 exerts antiproliferative effects in VSMCs in vivo and in vitro. Thus, the RXR may serve as a therapeutic target for vascular injury and intimal thickening. (c) 2006 Elsevier Inc. All rights reserved.