Increasing heart vascularisation after myocardial infarction using brain natriuretic peptide stimulation of endothelial and WT1+ epicardial cells

Elife. 2020 Nov 27:9:e61050. doi: 10.7554/eLife.61050.

Abstract

Brain natriuretic peptide (BNP) treatment increases heart function and decreases heart dilation after myocardial infarction (MI). Here, we investigated whether part of the cardioprotective effect of BNP in infarcted hearts related to improved neovascularisation. Infarcted mice were treated with saline or BNP for 10 days. BNP treatment increased vascularisation and the number of endothelial cells in all areas of infarcted hearts. Endothelial cell lineage tracing showed that BNP directly stimulated the proliferation of resident endothelial cells via NPR-A binding and p38 MAP kinase activation. BNP also stimulated the proliferation of WT1+ epicardium-derived cells but only in the hypoxic area of infarcted hearts. Our results demonstrated that these immature cells have a natural capacity to differentiate into endothelial cells in infarcted hearts. BNP treatment increased their proliferation but not their differentiation capacity. We identified new roles for BNP that hold potential for new therapeutic strategies to improve recovery and clinical outcome after MI.

Keywords: angiogenesis; brain natriuretic peptide; cell biology; endothelial cells; heart; mouse; precursors; regenerative medicine; stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cells, Cultured
  • Endothelial Cells / drug effects*
  • Gene Expression Regulation / drug effects
  • Male
  • Mice
  • Mice, Knockout
  • Natriuretic Peptide, Brain / pharmacology*
  • Pericardium / cytology*
  • Receptors, Atrial Natriuretic Factor / genetics
  • Receptors, Atrial Natriuretic Factor / metabolism
  • WT1 Proteins / genetics
  • WT1 Proteins / metabolism*

Substances

  • WT1 Proteins
  • WT1 protein, mouse
  • Natriuretic Peptide, Brain
  • Receptors, Atrial Natriuretic Factor
  • atrial natriuretic factor receptor A
  • atrial natriuretic factor receptor B