Perspectives for angiotensin profiling with liquid chromatography/mass spectrometry to evaluate ACE/ACE2 balance in endothelial dysfunction and vascular pathologies

Vascular injury, characterized by endothelial dysfunction, inflammation, structural remodeling, thrombosis and calcification leads to cardiovascular diseases. Angiotensin (Ang) II (1-8) - synthesized mainly by angiotensin converting enzyme (ACE) is the best characterized mediator of the renin-angiotensin system (RAS). This peptide initially identified by its vasoactive properties was found to play a major role in vascular response to insult. However, recent discovery of angiotensin converting enzyme 2 (ACE2) that produces vasoprotective Ang-(1-7) peptide highlighted complexity of the system and suggested that balance between ACE/Ang II and ACE2/Ang-(1-7) is fundamental in maintaining vascular homeostasis and its disorders are associated with cardiovascular pathology. There is therefore a need to develop methods for comprehensive analysis of biologically active Ang peptides and their metabolites of ACE/Ang II and ACE2/Ang-(1-7) axes. Liquid chromatography/mass spectrometry (LC/MS) is an analytical technique that offers potential for specific, simultaneous analysis of Ang peptides. With sensitivity added by application of preconcentration nanochromatography reaching picomolar concentrations, practically all Ang peptides identified so far could be quantified in biological samples. Ang profiling is important not only for understanding their physiological or pathological role but could also serve as an early diagnostic biomarker of endothelial dysfunction and cardiovascular pathology. It could also be used for monitoring the efficacy of the RAS-targeted therapies. Although, the methodology requires further improvements to adopt it for routine application, Ang peptide profiling with targeted LC/MS analysis might assess functional balance between ACE/Ang II and ACE2/Ang-(1-7) axes, facilitate our understanding of the cardiovascular pathology and enhance biomarker portfolio in cardiovascular diseases.