Towards a comprehensive endothelial biomarkers profiling and endothelium-guided pharmacotherapy

Pharmacol Rep. 2015 Aug;67(4):771-7. doi: 10.1016/j.pharep.2015.06.008. Epub 2015 Jun 29.

Abstract

Endothelial dysfunction has prognostic, diagnostic and therapeutic significance in cardiovascular disease, but the endothelial phenotype is still not measured routinely to stratify the cardiovascular risk and tailor therapy. Flow-mediated dilation (FMD), the gold-standard technique for the functional assessment of endothelial function that is increasingly used in clinical settings measures the nitric oxide (NO)-dependent function only. However, the endothelial dysfunction involves a plethora of pathophysiologically important biochemical changes beyond alterations in the NO bioavailability. Still, in many diseases, some plasma protein biomarkers reflecting the pro-thrombotic and the pro-inflammatory endothelial phenotypes have poor selectivity, specificity, and a weak predictive value if they are used alone. Therefore, a multi biomarker strategy seems to be a reasonable and promising alternative. Here, we propose a multi-biomarker strategy to diagnose the endothelial dysfunction and to monitor the efficacy of an endothelium-targeted therapy. This strategy is based on the panel of endothelial biomarkers, reflecting various aspects and mechanisms of dysfunctional endothelium. The potential of an advanced analytical platform like the ultra-high performance liquid chromatography (UHPLC) coupled to mass spectrometry-based multiple reaction monitoring for simultaneous quantification of multiple endothelial biomakers is also discussed.

Keywords: Biomarkers; Endothelium; Mass spectrometry; Pharmacotherapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cardiovascular Agents / administration & dosage*
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / drug therapy*
  • Cardiovascular Diseases / metabolism
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology
  • Humans
  • Risk Factors
  • Vasodilation / drug effects
  • Vasodilation / physiology

Substances

  • Biomarkers
  • Cardiovascular Agents