Danlou Tablet Protects Against Myocardial Infarction Through Promoting eNOS-Dependent Endothelial Protection and Angiogenesis

J Cardiovasc Transl Res. 2024 Apr;17(2):403-416. doi: 10.1007/s12265-023-10437-y. Epub 2023 Oct 2.

Abstract

Myocardial infarction (MI) is one of the leading causes of death worldwide. Danlou tablet (Dan) is an effective traditional Chinese medicine for cardiac protection, although the underlying mechanism was not fully understood. In this study, we used a murine MI model and demonstrated that Dan administration effectively attenuated myocardial apoptosis, cardiac remodeling, and heart failure post MI. Dan increased CD31-positive capillaries in MI hearts, and reduced the apoptosis and oxidative stress in human umbilical vein endothelial cells after oxygen-glucose deprivation stress, simultaneously with the activated HIF-1α/VEGFA/eNOS signaling. Moreover, inhibition of eNOS by L-NAME attenuated Dan-induced protection against MI, and abolished its effect in promoting angiogenesis and reducing endothelial apoptosis and oxidative stress. Collectively, Dan is beneficial to promote eNOS-dependent endothelial protection and angiogenesis thus protecting against MI. A deep understanding of Dan-induced protection might help promote clinical usage of Dan in MI treatment.

Keywords: Angiogenesis; Danlou tablet; Endothelial cell; Myocardial infarction; eNOS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis
  • Angiogenesis Inducing Agents / pharmacology
  • Animals
  • Apoptosis* / drug effects
  • Cells, Cultured
  • Disease Models, Animal*
  • Drugs, Chinese Herbal* / pharmacology
  • Human Umbilical Vein Endothelial Cells* / drug effects
  • Human Umbilical Vein Endothelial Cells* / enzymology
  • Human Umbilical Vein Endothelial Cells* / metabolism
  • Human Umbilical Vein Endothelial Cells* / pathology
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Male
  • Mice, Inbred C57BL*
  • Myocardial Infarction* / enzymology
  • Myocardial Infarction* / metabolism
  • Myocardial Infarction* / pathology
  • Myocardial Infarction* / prevention & control
  • Neovascularization, Physiologic* / drug effects
  • Nitric Oxide Synthase Type III* / metabolism
  • Oxidative Stress* / drug effects
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Signal Transduction*
  • Tablets
  • Vascular Endothelial Growth Factor A / metabolism
  • Ventricular Function, Left / drug effects
  • Ventricular Remodeling* / drug effects

Substances

  • Nitric Oxide Synthase Type III
  • Nos3 protein, mouse
  • Drugs, Chinese Herbal
  • NOS3 protein, human
  • Vascular Endothelial Growth Factor A
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Hif1a protein, mouse
  • Angiogenesis Inducing Agents
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Pecam1 protein, mouse
  • Tablets
  • VEGFA protein, human
  • PECAM1 protein, human