Zhang Wei, Zhang Liming, Zhang Xiaosi
Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Metro-Medic Clinic, Montreal, Quebec, Canada.
Ann Transl Med. 2022 Jun;10(12):700. doi: 10.21037/atm-22-2113.
Atherosclerosis (AS) is associated with inflammation and abnormal proliferation and migration of vascular smooth muscle cells (VSMCs). Genistein may curtail the migration of VSMCs. Therefore, explorations are required to determine the molecular mechanism of genistein in AS. In this context, animal and cell models were developed to ascertain mechanisms of genistein in AS by modulating VSMC activities.
Genistein treatment and ectopic expression of lectin-like oxidized LDL receptor-1 () were conducted in high-fat diet-induced AS rats, followed by analyses of atherosclerotic plaque lesion areas and lipid deposition using Oil Red O and hematoxylin and eosin (HE) staining. The isolated VSMCs were stimulated with oxidized low-density lipoprotein (ox-LDL). Following genistein treatment combined with gain- and loss-of-function experiments in ox-LDL-exposed VSMCs, viability, migration, intracellular lipid deposition, intracellular cholesterol content, and L-type calcium (L-Ca) channel currents were assessed using Cell Counting Kit-8 (CCK-8), scratch test, Oil Red O staining, enzymatic colorimetry, and patch-clamp experiments, respectively. Western blot analysis was performed to evaluate the protein expression of proto-oncogene, non-receptor tyrosine kinase (), calcium voltage-gated channel subunit alpha1 C (), and .
Genistein treatment counteracted upregulated phosphorylation, and expression, and L-Ca channel currents in aortic tissues of AS rats and ox-LDL-exposed VSMCs. Genistein deceased L-Ca channel currents by downregulating , and augmented expression by acting on the L-Ca channel subunit . The ox-LDL-induced VSMC proliferation, migration, and foaming of VSMCs were reduced by genistein treatment, silencing , , or , or suppressing L-Ca channels. Genistein treatment diminished atherosclerotic plaque lesion formation and lipid deposition, and these results were annulled by upregulating .
Collectively, genistein might block the // axis to impede ox-LDL-induced VSMC proliferation, migration, and foaming and alleviate AS formation.
动脉粥样硬化（AS）与炎症以及血管平滑肌细胞（VSMC）的异常增殖和迁移有关。染料木黄酮可能会抑制VSMC的迁移。因此，需要进行探索以确定染料木黄酮在AS中的分子机制。在此背景下，建立了动物和细胞模型，以通过调节VSMC活性来确定染料木黄酮在AS中的作用机制。
对高脂饮食诱导的AS大鼠进行染料木黄酮处理并异位表达凝集素样氧化型低密度脂蛋白受体1（），然后使用油红O以及苏木精和伊红（HE）染色分析动脉粥样硬化斑块病变面积和脂质沉积。用氧化型低密度脂蛋白（ox-LDL）刺激分离的VSMC。在ox-LDL处理的VSMC中进行染料木黄酮处理并结合功能获得和功能丧失实验后，分别使用细胞计数试剂盒-8（CCK-8）、划痕试验、油红O染色、酶比色法和膜片钳实验评估细胞活力、迁移、细胞内脂质沉积、细胞内胆固醇含量和L型钙（L-Ca）通道电流。进行蛋白质免疫印迹分析以评估原癌基因、非受体酪氨酸激酶（）、钙电压门控通道亚基α1 C（）和的蛋白表达。
染料木黄酮处理可抵消AS大鼠主动脉组织和ox-LDL处理的VSMC中上调的磷酸化、和表达以及L-Ca通道电流。染料木黄酮通过下调降低L-Ca通道电流，而通过作用于L-Ca通道亚基增加表达。染料木黄酮处理、沉默、或或抑制L-Ca通道可减少ox-LDL诱导的VSMC增殖、迁移和VSMC泡沫化。染料木黄酮处理减少了动脉粥样硬化斑块病变形成和脂质沉积，而上调可消除这些结果。
总体而言，染料木黄酮可能会阻断//轴，以阻止ox-LDL诱导的VSMC增殖、迁移和泡沫化，并减轻AS的形成。
