Molecular mechanisms associated with Angiotensin-converting enzyme-inhibitory peptide activity on vascular extracellular matrix remodeling

Cardiology. 2014;127(4):247-55. doi: 10.1159/000356951. Epub 2014 Jan 24.

Abstract

Objective: This paper aimed to investigate the molecular mechanisms associated with angiotensin-converting enzyme (ACE)-inhibitory peptide activity involved in vascular extracellular matrix (ECM) remodeling. Therefore, changes in collagen fibers, elastic fibers and laminin were assessed in the left common carotid artery (LCCA).

Methods: We selected 10-week-old male spontaneously hypertensive rats to study the expression levels of matrix metalloproteinases (MMPs), transforming growth factor, angiotensin (Ang) II and nuclear factor (NF)-p65 in the wall of carotid arteries.

Results: Compared to the control group, laminin expression was significantly increased (p < 0.05) in the vascular endothelium of the LAP (a homemade ACE-inhibitory peptide, named by ourselves) group, whereas the percentage of elastic/collagen fibers in the LCCA vascular area was significantly decreased (p < 0.0001) in the LAP group. Immune blots of MMP-2, MMP-9, NF-p65 and AngII were significantly reduced in the LCCA wall in the LAP group.

Conclusion: Vascular ECM remodeling may be related to the inhibitory action of LAP on ECM deposition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / metabolism
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Blood Pressure / drug effects
  • Blood Vessels / drug effects*
  • Blood Vessels / metabolism
  • Carotid Artery, Common / drug effects
  • Collagen / metabolism
  • Elastic Tissue / metabolism
  • Extracellular Matrix / drug effects*
  • Extracellular Matrix / metabolism
  • Heart Rate / drug effects
  • Inflammation / blood
  • Lactoferrin / pharmacology*
  • Laminin / metabolism
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Peptide Fragments / pharmacology*
  • Random Allocation
  • Rats
  • Rats, Inbred SHR
  • Transcription Factor RelA / metabolism
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Laminin
  • Peptide Fragments
  • Tgfb1 protein, rat
  • Transcription Factor RelA
  • Transforming Growth Factor beta1
  • leucyl-arginyl-prolyl-valyl-alanyl-alanine
  • Angiotensin II
  • Collagen
  • Lactoferrin
  • Matrix Metalloproteinase 2
  • Mmp2 protein, rat
  • Matrix Metalloproteinase 9
  • Mmp9 protein, rat