title: Towards a comprehensive endothelial biomarkers profiling and endothelium-guided pharmacotherapy.
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.
authors: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Kraków, Poland; Department of Pharmacokinetics and Physical Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
authors: Maria
authors: M
authors: Walczak
authors: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Kraków, Poland; Department of Pharmacokinetics and Physical Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
authors: Joanna
authors: J
authors: Suraj
authors: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Kraków, Poland; Department of Pharmacokinetics and Physical Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
authors: Kamil
authors: K
authors: Kus
authors: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Kraków, Poland; Department of Pharmacokinetics and Physical Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
authors: Agnieszka
authors: A
authors: Kij
authors: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Kraków, Poland.
authors: Agnieszka
authors: A
authors: Zakrzewska
authors: Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Kraków, Poland; Department of Experimental Pharmacology, Chair of Pharmacology, Jagiellonian University, Medical College, Kraków, Poland. Electronic address: stefan.chlopicki@jcet.eu.
authors: Stefan
authors: S
authors: Chlopicki
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D012307:Risk Factors; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D015415:Biomarkers; D002317:Cardiovascular Agents
keywords: Biomarkers; Endothelium; Mass spectrometry; Pharmacotherapy