Vasoactive effect of fibronectin-derived epiviosamine-1 and related peptides in quiescent and stress models

Microcirculation. 2017 Aug;24(6):10.1111/micc.12369. doi: 10.1111/micc.12369.

Abstract

Objective: Following thermal burn injury, plasma fibronectin degrades within the interstitium; one possible product is EVA-1, PSHISKYILRWRPK found within the FNIII1 . EVA-1 ameliorates thermal burn injury progression, and binds to and enhances PDGF-BB in promoting cell metabolism, growth and survival; shorter related peptides lose these abilities. Here we study the effect of EVA-1 and shorter peptides for their vasoactivity under quiescent and stress conditions.

Methods: Using the hamster cheek pouch intravital microscopy model, five EVA-1 related peptides were applied to small arterioles via micropipette (10-16 -10-4 mol L-1 ) in quiescent tissue and after defined stress: nitric oxide or heat.

Results: Peak dilation occurred with nanomolar doses (longer peptides) or below (shorter peptides), blocked by propranolol (beta-adrenergic receptor antagonist). Micromolar doses of the same peptides induced only constriction, not antagonized by phentolamine (alpha-adrenergic receptor antagonist). Scrambled variants of two peptides yielded only constriction, suggesting constriction might be due peptide charge. Each stressor caused a left shift in dilation response, blocked by carazolol.

Conclusions: Thus, this important region of FNIII1 contains sequences that have a gradation of biological functions dependent on the length of the peptide sequence, with increased efficacy for dilation following stressors.

Keywords: bioactive peptides; endothelial dysfunction; fibroblast; fibronectin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cricetinae
  • Fibronectins / metabolism*
  • Fibronectins / pharmacology
  • Hot Temperature
  • Intravital Microscopy
  • Nitric Oxide
  • Peptides / metabolism
  • Peptides / pharmacology*
  • Stress, Physiological
  • Vasoconstriction / drug effects*
  • Vasodilation / drug effects*

Substances

  • Fibronectins
  • Peptides
  • Nitric Oxide