Down-regulation of VCAM-1 in bone mesenchymal stem cells reduces inflammatory responses and apoptosis to improve cardiac function in rat with myocardial infarction

Int Immunopharmacol. 2021 Dec;101(Pt A):108180. doi: 10.1016/j.intimp.2021.108180. Epub 2021 Oct 1.

Abstract

Background: Bone mesenchymal stem cells (BMSCs) has been well known to exert therapeutic potential for patients with myocardial infarction (MI). VCAM-1 can promote the migration of lymphocytes to the inflammatory zone. In the present study, we tried to explore whether VCAM-1 silenced-BMSCs have better therapeutic effects on MI.

Methods: BMSCs were isolated and cultured followed by treatment of a lentivirus silencing VCAM-1 and NF-κB activator (PMA). Besides, MI rat models were also established and injected with treated BMSCs to detect the effect of VCAM-1 silenced-BMSCs in MI, as evidenced by detection of cardiac function, survival of rats within 72 h, infarct size and myocardial cell apoptosis. Moreover, the expression of NF-κB-regulated gene products was also determined.

Results: The implantation of sh-VCAM-1 BMSCs into MI rats resulted in more reductions in myocardial infarct size as well as myocardial cell apoptosis, improved cardiac function, the number of survived rats within 72 h, and survival time within 72 h compared with the individual treatments of either BMSCs or control. In addition, transplanted BMSCs down-regulated the expression of NF-κB-p65, MMP-9, TNF-α, and Bax, and up-regulated VEGF and Bcl-2 in myocardial tissue, which could be further enhanced by sh-VCAM-1 and rescued by PMA.

Conclusion: Our study demonstrated that silencing VCAM-1 in BMSCs could inhibit inflammation and apoptosis, thus improving cardiac function in MI.

Keywords: Bone mesenchymal stem cells; Cardiac function; Myocardial infarction; NF-κB pathway; PMA; VCAM-1.

MeSH terms

  • Animals
  • Apoptosis / immunology
  • Bone and Bones / cytology
  • Cells, Cultured
  • Disease Models, Animal
  • Down-Regulation
  • Humans
  • Male
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / immunology*
  • Mesenchymal Stem Cells / metabolism
  • Myocardial Infarction / immunology
  • Myocardial Infarction / pathology
  • Myocardial Infarction / therapy*
  • Myocardium / immunology
  • Myocardium / pathology
  • Myocytes, Cardiac
  • NF-kappa B / metabolism
  • Primary Cell Culture
  • Rats
  • Signal Transduction / immunology
  • Vascular Cell Adhesion Molecule-1 / genetics
  • Vascular Cell Adhesion Molecule-1 / metabolism*

Substances

  • NF-kappa B
  • Vascular Cell Adhesion Molecule-1