Department of Bioscience and Laboratory Medicine, Hirosaki University Graduate School of Health Sciences, Hirosaki 036-8564, Japan.
Faculty of Agriculture and Life Science, Hirosaki University, Hirosaki 036-8561, Japan.
Nutrients. 2021 Feb 8;13(2):560. doi: 10.3390/nu13020560.
Estrogen exerts cardioprotective effects in menopausal women. Phytoestrogens are plant-derived substances exhibiting estrogenic activity that could beneficially affect vascular health. We previously demonstrated that blackcurrant ( L.) extract (BCE) treatment exerted beneficial effects on vascular health via phytoestrogenic activity in ovariectomized (OVX) rats, which are widely used as menopausal animal models. Here, we examined whether BCE treatment reduced elastin degradation and prevented pathological vascular remodeling in OVX rats fed a regular diet (OVX Control) or a 3% BCE-supplemented diet (OVX BCE), compared with sham surgery rats fed a regular diet (Sham) for 3 months. The results indicated a lower staining intensity of elastic fibers, greater elastin fragmentation, and higher α-smooth muscle actin protein expression in OVX Control rats than in OVX BCE and Sham rats. Pathological vascular remodeling was only observed in OVX Control rats. Additionally, we investigated matrix metalloproteinase (MMP)-12 mRNA expression levels to elucidate the mechanism underlying elastin degradation, revealing significantly upregulated MMP-12 mRNA expression in OVX Control rats compared with that in Sham and OVX BCE rats. Together, we identify BCE as exerting a vascular protective effect through reduced MMP-12 expression and vascular smooth muscle cell proliferation. To our knowledge, this is the first report indicating that BCE might protect against elastin degradation and pathological vascular remodeling during menopause.
雌激素对绝经后妇女具有心脏保护作用。植物雌激素是具有雌激素活性的植物来源物质,可能对血管健康有益。我们之前的研究表明,黑加仑(L.)提取物(BCE)通过植物雌激素活性对去卵巢(OVX)大鼠的血管健康产生有益影响,OVX 大鼠被广泛用作绝经动物模型。在这里,我们研究了 3 个月的普通饮食(OVX 对照组)或 3% BCE 补充饮食(OVX BCE 组)喂养的 BCE 治疗是否会减少弹性蛋白降解并预防 OVX 大鼠的病理性血管重塑,与接受假手术的普通饮食喂养的 Sham 大鼠(Sham)相比。结果表明,与 OVX BCE 和 Sham 大鼠相比,OVX 对照组大鼠的弹性纤维染色强度较低,弹性蛋白片段化程度较高,α-平滑肌肌动蛋白蛋白表达水平较高。仅在 OVX 对照组大鼠中观察到病理性血管重塑。此外,我们研究了基质金属蛋白酶(MMP)-12 mRNA 表达水平,以阐明弹性蛋白降解的机制,结果表明 OVX 对照组大鼠的 MMP-12 mRNA 表达水平明显高于 Sham 和 OVX BCE 大鼠。综上所述,我们发现 BCE 通过降低 MMP-12 表达和血管平滑肌细胞增殖来发挥血管保护作用。据我们所知,这是第一项表明 BCE 可能预防绝经期间弹性蛋白降解和病理性血管重塑的报告。