Partial IGF-1 deficiency is sufficient to reduce heart contractibility, angiotensin II sensibility, and alter gene expression of structural and functional cardiac proteins

PLoS One. 2017 Aug 14;12(8):e0181760. doi: 10.1371/journal.pone.0181760. eCollection 2017.

Abstract

Circulating levels of IGF-1 may decrease under several circumstances like ageing, metabolic syndrome, and advanced cirrhosis. This reduction is associated with insulin resistance, dyslipidemia, progression to type 2 diabetes, and increased risk for cardiovascular diseases. However, underlying mechanisms between IGF-1 deficiency and cardiovascular disease remain elusive. The specific aim of the present work was to study whether the partial IGF-1 deficiency influences heart and/or coronary circulation, comparing vasoactive factors before and after of ischemia-reperfusion (I/R). In addition, histology of the heart was performed together with cardiac gene expression for proteins involved in structure and function (extracellular matrix, contractile proteins, active peptides); carried out using microarrays, followed by RT-qPCR confirmation of the three experimental groups. IGF-1 partial deficiency is associated to a reduction in contractility and angiotensin II sensitivity, interstitial fibrosis as well as altered expression pattern of genes involved in extracellular matrix proteins, calcium dynamics, and cardiac structure and function. Although this work is descriptive, it provides a clear insight of the impact that partial IGF-1 deficiency on the heart and establishes this experimental model as suitable for studying cardiac disease mechanisms and exploring therapeutic options for patients under IGF-1 deficiency conditions.

MeSH terms

  • Angiotensin II / pharmacology*
  • Animals
  • Body Weight / drug effects
  • Bradykinin / pharmacology
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism
  • Gene Expression Regulation / drug effects*
  • Hemodynamics / drug effects
  • Insulin-Like Growth Factor I / deficiency*
  • Insulin-Like Growth Factor I / metabolism
  • Mice, Transgenic
  • Myocardial Contraction / drug effects*
  • Myocardial Contraction / genetics
  • Myocardium / metabolism
  • Myocardium / pathology
  • Organ Size / drug effects
  • Perfusion
  • Real-Time Polymerase Chain Reaction
  • Vasoconstriction / drug effects
  • Vasodilation / drug effects

Substances

  • Angiotensin II
  • Insulin-Like Growth Factor I
  • Bradykinin

Grants and funding

This work was supported by Fundación de Investigación Hospitales de Madrid and Tecnológico de Monterrey. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.