工程化的白藜芦醇负载纤维支架通过硫氧还蛋白-1 介导的 VEGF 通路促进功能性心脏修复和再生。
Engineered resveratrol-loaded fibrous scaffolds promotes functional cardiac repair and regeneration through Thioredoxin-1 mediated VEGF pathway.
机构信息
Molecular Cardiology and Angiogenesis Laboratory, University of Connecticut Health, Farmington 06030, CT, USA; Department of Surgery, University of Connecticut Health, Farmington 06030, CT, USA.
Molecular Cardiology and Angiogenesis Laboratory, University of Connecticut Health, Farmington 06030, CT, USA; Department of Surgery, University of Connecticut Health, Farmington 06030, CT, USA; Stanley J. Dudrick, Department of Surgery, Saint Mary's Hospital, Waterbury 06706, CT, USA.
出版信息
Int J Pharm. 2021 Mar 15;597:120236. doi: 10.1016/j.ijpharm.2021.120236. Epub 2021 Feb 1.
Despite recent advancements, mortality due to coronary heart disease (CHD) remains high. Recently, the use of tissue-engineered grafts and scaffolds has emerged as a candidate for supporting the myocardium after an ischemic event. Resveratrol is a naturally occurring plant-based non-flavonoid polyphenolic compound found in many natural foods, including grapes and red wine. We embedded resveratrol in a polycaprolactone (PCL) scaffold and evaluated the cardio-therapeutic effects in a murine model of myocardial infarction (MI), with animals being grouped into Sham (S), Myocardial Infarction (MI), MI + PCL, and MI + PCL-Resveratrol (MI + PCL-R). After 4 and 8 weeks, echocardiography was performed to assess ejection fraction (EF) and fractional shortening (FS), which was followed by immunohistochemistry and immunofluorescence analysis at 8 weeks. The MI + PCL-R group showed a significant improvement in EF and FS compared with the MI + PCL group at 4 and 8-weeks post-surgery. PCL-R scaffolds treated hearts revealed decreased inflammatory cell infiltration, improved collagen extracellular matrix (ECM) secretion and blood vessel network formation following MI. The immunofluorescence analysis revealed resveratrol-loaded scaffolds promote increased expression of cTnT, Cx-43, Trx-1, and VEGF proteins. This study reports resveratrol-mediated rescue of ischemic myocardium when delivered through a biodegradable polymeric scaffold system after MI.
尽管最近取得了进展，但冠心病（CHD）导致的死亡率仍然很高。最近，组织工程化移植物和支架的使用已成为缺血事件后支持心肌的候选方法。白藜芦醇是一种天然存在的植物非黄酮多酚化合物，存在于许多天然食物中，包括葡萄和红酒。我们将白藜芦醇嵌入聚己内酯（PCL）支架中，并在心肌梗死（MI）的小鼠模型中评估了其心脏治疗效果，将动物分为假手术组（Sham，S）、心肌梗死组（MI）、心肌梗死+PCL 组（MI+PCL）和心肌梗死+PCL-白藜芦醇组（MI+PCL-R）。在 4 周和 8 周后，进行超声心动图评估射血分数（EF）和缩短分数（FS），然后在 8 周时进行免疫组织化学和免疫荧光分析。与 MI+PCL 组相比，MI+PCL-R 组在手术后 4 周和 8 周时 EF 和 FS 均有显著改善。经 MI 治疗后，PCL-R 支架处理的心脏显示炎症细胞浸润减少，胶原细胞外基质（ECM）分泌和血管网络形成改善。免疫荧光分析显示，负载白藜芦醇的支架可促进 cTnT、Cx-43、Trx-1 和 VEGF 蛋白的表达增加。这项研究报告了在 MI 后通过生物可降解聚合物支架系统输送时，白藜芦醇介导的缺血性心肌挽救。
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