Background: Endothelial dysfunction is one of the earliest vascular manifestations in the pathogenesis of cardiovascular disease. Noninvasive, simple, and inexpensive methods of endothelial function assessment are therefore needed. Methods: Microvascular endothelial function was assessed in coronary artery disease (CAD) patients by flow mediated skin fluorescence (FMSF), based on measurements of reduced form of nicotinamide adenine dinucleotide (NADH) fluorescence intensity during brachial artery occlusion (ischemic response [IRmax]) and immediately after occlusion (hyperemic response [HRmax]). Additionally, plasma levels of asymmetric dimethylarginine (ADMA) and endothelin-1 (ET-1) were measured to assess the association between biochemical markers and microvascular function evaluated in vivo by FMSF. Results: A significant inverse correlation was found between ADMA levels and hyperemic response (r = -0.534, p = 0.003), while ET-1 levels were inversely related to the ischemic response (r= -0.575, p = 0.001). Both IR and HR were found lowest in patients with advanced CAD and diabetes. When the repeatability of the method was tested, the intraclass correlation coefficient for IRmax and HRmax were 0.985 (p < 0.001) and 0.914 (p < 0.001), respectively. Moreover, in Bland and Altman analysis, both variables IRmax and HRmax showed good agreement in repeated measurements. Conclusions: In this pilot study, it was demonstrated that NADH fluorescence measured by FMSF device in CAD patients was associated with established plasma endothelial markers, and that both ischemic and hyperemic response were blunted in patients with advanced disease and diabetes. Furthermore, FMSF device showed excellent repeatability and good agreement for repeated measurements. However, further study is warranted to confirm these results in a larger patient cohort.

Endothelial cells are a preferential target for SARS-CoV-2 infection. Previously, we have reported that vascular adenosine deaminase 1 (ADA1) may serve as a biomarker of endothelial activation and vascular inflammation, while ADA2 plays a critical role in monocyte and macrophage function. In this study, we investigated the activities of circulating ADA isoenzymes in patients 8 weeks after mild COVID-19 and related them to the parameters of inflammation and microvascular/endothelial function. Post-COVID patients revealed microvascular dysfunction associated with the changes in circulating parameters of endothelial dysfunction and inflammatory activation. Interestingly, serum total ADA and ADA2 activities were diminished in post-COVID patients, while ADA1 remained unchanged in comparison to healthy controls without a prior diagnosis of SARS-CoV-2 infection. While serum ADA1 activity tended to positively correspond with the parameters of endothelial activation and inflammation, sICAM-1 and TNFα, serum ADA2 activity correlated with IL-10. Simultaneously, post-COVID patients had lower circulating levels of ADA1-anchoring protein, CD26, that may serve as an alternative receptor for virus binding. This suggests that after the infection CD26 is rather maintained in cell-attached form, enabling ADA1 complexing. This study points to the possible role of ADA isoenzymes in cardiovascular complications after mild COVID-19.

Vascular aging is a physiological, multifactorial process that involves every type of vessel, from large arteries to microcirculation. This manifests itself as impaired vasomotor function, altered secretory phenotype, deteriorated intercellular transport function, structural remodeling, and aggravated barrier function between the blood and the vascular smooth muscle layer. Iron disorders, particularly iron overload, may lead to oxidative stress and, among other effects, vascular aging. The elevated transferrin saturation and serum iron levels observed in iron overload lead to the formation of a non-transferrin-bound iron (NTBI) fraction with high pro-oxidant activity. NTBI can induce the production of reactive oxygen species (ROS), which induce lipid peroxidation and mediate iron-related damage as the elements of oxidative stress in many tissues, including heart and vessels’ mitochondria. However, the available data make it difficult to precisely determine the impact of iron metabolism disorders on vascular aging; therefore, the relationship requires further investigation. Our study aims to present the current state of knowledge on vascular aging in patients with deteriorated iron metabolism.