Leptin and endothelin-1 mediated increased extracellular matrix protein production and cardiomyocyte hypertrophy in diabetic heart disease

Diabetes Metab Res Rev. 2009 Jul;25(5):452-63. doi: 10.1002/dmrr.964.


Background: We investigated the role of leptin and its interaction with endothelin 1 (ET-1) in fibronectin (FN) synthesis and cardiomyocyte hypertrophy, two characteristic features of diabetic cardiomyopathy.

Methods: Endothelial cells [human umbilical vein endothelial cells (HUVECs)] were examined for FN production and neonatal rat cardiomyocytes for hypertrophy, following incubation with glucose, ET-1, leptin and specific blockers. FN, ET-1, leptin and leptin receptors mRNA expression and FN protein were measured. Myocytes were also morphometrically examined. Furthermore, hearts from streptozotocin-diabetic rats were analysed.

Results: Glucose caused increased FN mRNA and protein expression in HUVECs and cardiomyocytes hypertrophy along with upregulation of ET-1 mRNA, leptin mRNA and protein. Glucosemimetic effects were seen with leptin and ET-1. Leptin receptor antagonist (leptin quadruple mutant) and dual endothelin A endothelin B (ETA/ETB) receptor blocker bosentan normalized such abnormalities. Hearts from the diabetic animals showed hypertrophy and similar mRNA changes.

Conclusion: These data indicate that in diabetes increased FN production and cardiomyocyte hypertrophy may be mediated through leptin with its interaction with ET-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Cells, Cultured
  • Diabetic Angiopathies / metabolism
  • Endothelial Cells / metabolism*
  • Endothelin-1 / genetics
  • Endothelin-1 / physiology*
  • Extracellular Matrix Proteins / metabolism
  • Fibronectins / genetics
  • Fibronectins / metabolism*
  • Humans
  • Hypertrophy
  • Leptin / genetics
  • Leptin / physiology*
  • Male
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / pathology
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Leptin / genetics
  • Receptors, Leptin / metabolism
  • Statistics, Nonparametric
  • Umbilical Veins / cytology
  • Umbilical Veins / metabolism


  • Endothelin-1
  • Extracellular Matrix Proteins
  • Fibronectins
  • Leptin
  • RNA, Messenger
  • Receptors, Leptin