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.

Homoarginine and all‐cause mortality: A systematic review and meta‐analysis

“…1 An impairment in endothelial function and NO synthesis, a phenomenon generally associated with the presence of cardiovascular risk factors such as hypertension, diabetes and hypercholesterolaemia, leads to functional and structural alterations of the arterial wall that ultimately favour the onset and progression of atherosclerosis. 4,5 There is emerging evidence that homoarginine, a basic amino acid that is synthesized from L-arginine by the enzyme arginine:glycine amidinotransferase, exerts beneficial effects not only on endothelial function but also on markers of vascular homoeostasis and cardiac function. 3 Therefore, the identification of endogenous factors and drugs that exert salutary effects on endothelial function remains a priority in cardiovascular research.…”

Functional and Biochemical Endothelial Profiling In Vivo in a Murine Model of Endothelial Dysfunction; Comparison of Effects of 1-Methylnicotinamide and Angiotensin-converting Enzyme Inhibitor

“…Prognostic value of biochemical measurements of endothelial biomarkers is still not widely accepted (Walczak et al, 2015). However, endothelial function measurements based on the assessment of impairment of NO-dependent vasodilatation in the coronary and peripheral circulation have prognostic importance in predicting adverse cardiovascular events (Schächinger et al, 2000; Halcox et al, 2002).…”

Rapid biochemical profiling of endothelial dysfunction in diabetes, hypertension and cancer metastasis by hierarchical cluster analysis of Raman spectra

“…Proper function of endothelium guards the health of the cardiovascular system, while endothelial dysfunction leads to cardiovascular diseases, including diabetes mellitus, hypertension and atherosclerosis . A profile of biochemical mediators produced by dysfunctional endothelium differs from that of healthy endothelium as well as chemical contents detected by Raman imaging …”

“…[29] Proper function of endothelium guards the health of the cardiovascular system, while endothelial dysfunction leads to cardiovascular diseases, including diabetes mellitus, hypertension and atherosclerosis. [30] A profile of biochemical mediators produced by dysfunctional endothelium differs from that of healthy endothelium [30][31][32] as well as chemical contents detected by Raman imaging. [33][34][35] In this work, we aimed to set up the methodology for the rapid biochemical profiling of endothelial dysfunction based on HCA used for discrimination of single Raman spectra, recorded with the integration time of 0.2 s, of vascular endothelium in ex vivo aorta.…”