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Published on: September 15, 2017
Towards a comprehensive endothelial biomarkers profiling and endothelium-guided pharmacotherapy
Maria Walczak1, Joanna Suraj1, Kamil Kus1
1Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Kraków, Poland; Department of Pharmacokinetics and Physical Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
Insights
A multi-biomarker strategy can improve the diagnosis of endothelial dysfunction and monitor therapy effectiveness. This approach captures various aspects of endothelial health beyond nitric oxide (NO) function, offering a more comprehensive assessment for cardiovascular disease management.
Area of Science:
- Cardiovascular Medicine
- Biomarker Discovery
- Endothelial Biology
Background:
- Endothelial dysfunction is crucial in cardiovascular disease but not routinely measured for risk stratification or therapy tailoring.
- Current gold-standard flow-mediated dilation (FMD) assesses only nitric oxide (NO)-dependent function, missing broader pathophysiological changes.
- Existing single plasma biomarkers for pro-thrombotic and pro-inflammatory endothelial phenotypes lack specificity and predictive value.
Purpose of the Study:
- To propose a multi-biomarker strategy for diagnosing endothelial dysfunction.
- To enable monitoring of endothelium-targeted therapy efficacy.
- To provide a comprehensive assessment of endothelial health by evaluating diverse pathophysiological mechanisms.
Main Methods:
- Development of a multi-biomarker panel reflecting various aspects of endothelial dysfunction.
- Utilizing advanced analytical platforms, such as ultra-high performance liquid chromatography (UHPLC) coupled to mass spectrometry.
- Implementing multiple reaction monitoring (MRM) for simultaneous quantification of multiple endothelial biomarkers.
Main Results:
- The proposed strategy integrates multiple biomarkers to overcome the limitations of single markers.
- Simultaneous quantification of diverse endothelial biomarkers provides a more accurate picture of endothelial health.
- The multi-biomarker approach offers improved diagnostic and prognostic capabilities compared to current methods.
Conclusions:
- A multi-biomarker strategy is a promising alternative for diagnosing endothelial dysfunction and monitoring therapy.
- This approach enhances the assessment of cardiovascular risk and personalization of treatment.
- Advanced analytical techniques are essential for the successful implementation of multi-biomarker strategies in clinical practice.
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.
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