CAV1 Protein Encapsulated in Mouse BMSC-Derived Extracellular Vesicles Alleviates Myocardial Fibrosis Following Myocardial Infarction by Blocking the TGF-β1/SMAD2/c-JUN Axis

J Cardiovasc Transl Res. 2024 Jun;17(3):523-539. doi: 10.1007/s12265-023-10472-9. Epub 2023 Dec 13.

Abstract

Extracellular vesicles (EVs) derived from mouse bone marrow mesenchymal stem cells (mBMSCs) convey the CAV1 protein, influencing the TGF-β1/SMAD2/c-JUN pathway and thus the molecular mechanisms underlying myocardial fibrosis (MF) post-myocardial infarction (MI). Through various experimental methods, including transmission electron microscopy, Nanosight analysis, Western blot, ELISA, and qRT-PCR, we isolated, purified, and identified EVs originating from mBMSCs. Bioinformatics and experimental findings show a reduced expression of CAV1 in myocardial fibrosis tissue. Furthermore, our findings suggest that mBMSC-EVs can deliver CAV1 to cardiac fibroblasts (CFs) and that silencing CAV1 in mBMSC-EVs promotes CF fibrosis. In vivo studies further corroborated these findings. In conclusion, mBMSC-EVs mitigate myocardial fibrosis in MI mice by delivering the CAV1 protein, inhibiting the TGF-β1/SMAD2/c-JUN pathway.

Keywords: Bone marrow–derived mesenchymal stem cells; CAV1; Extracellular vesicles; Myocardial infarction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caveolin 1* / genetics
  • Caveolin 1* / metabolism
  • Cells, Cultured
  • Disease Models, Animal*
  • Extracellular Vesicles* / metabolism
  • Extracellular Vesicles* / transplantation
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Fibrosis*
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Male
  • Mesenchymal Stem Cells* / metabolism
  • Mice, Inbred C57BL*
  • Myocardial Infarction* / metabolism
  • Myocardial Infarction* / pathology
  • Myocardium* / metabolism
  • Myocardium* / pathology
  • Proto-Oncogene Proteins c-jun* / metabolism
  • Signal Transduction*
  • Smad2 Protein* / metabolism
  • Transforming Growth Factor beta1* / metabolism

Substances

  • Smad2 Protein
  • Transforming Growth Factor beta1
  • Smad2 protein, mouse
  • Tgfb1 protein, mouse
  • Proto-Oncogene Proteins c-jun
  • Cav1 protein, mouse
  • Caveolin 1
  • JNK Mitogen-Activated Protein Kinases