Đokić, Vladimir

Circulating extracellular vesicles, proinflammatory/pro-oxidant metabolites, and history of preeclampsia may be used as biomarkers for diagnosis of early CAC in postmenopausal women.

Background We aimed to assess the longitudinal changes of glycocalyx, a proteoglycan/glycoprotein layer that lines and protects endothelial cells in normotensive pregnancies (NPs); to correlate glycocalyx parameters with kidney injury markers (podocin‐positive to nephrin‐positive [P/N] ratio); and to explore changes in P/N ratio in preeclampsia. Methods Plasma and urine samples and glycocalyx measurements using side‐stream darkfield imaging were collected at each trimester from pregnant women (n=31). Plasma glycocalyx components were measured by ELISA, and urinary P/N‐positive extracellular vesicles by flow cytometry. Results In NPs (n=26), glycocalyx degradation increased from the first to the second trimester ( P =0.008) and returned to first‐trimester values in the third trimester ( P =0.008). Microvascular perfusion decreased from the first to the second trimester ( P =0.006) and increased back to first‐trimester values by the third trimester ( P =0.039). Plasma syndecan 1 level showed a steady increase from the first to the second trimester ( P <0.001) and further in the third trimester ( P <0.001); hyaluronic acid increased from the first to the second trimester ( P =0.016) without further changes. Glycocalyx degradation was associated with an increase in P/N ratio from the first to the second trimester of NPs and remained stable through the third trimester. P/N ratio strongly correlated with elevated syndecan 1 and hyaluronic acid levels in the third trimester. Comparison of P/N ratios between NP and preeclampsia (n=5) showed higher values in preeclampsia across all trimesters ( P =0.028). Conclusions Glycocalyx changes during NPs are associated with elevated urinary podocyte markers. Increase in P/N ratio across NPs, and further in preeclampsia, suggests that podocyte injury in preeclampsia is extension of physiological changes in pregnancy, which may predate its clinical presentation.

Here we have shown for the first time altered expression of the vascular smooth muscle (VSM) KATP channel subunits in segments of the human internal mammary artery (HIMA) in patients with type-2 diabetes mellitus (T2DM). Functional properties of vascular KATP channels in the presence of T2DM, and the interaction between its subunits and endogenous ligands known to relax this vessel, were tested using the potassium (K) channels opener, pinacidil. HIMA is the most commonly used vascular graft in cardiac surgery. Previously it was shown that pinacidil relaxes HIMA segments through interaction with KATP (SUR2B/Kir6.1) vascular channels, but it is unknown whether pinacidil sensitivity is changed in the presence of T2DM, considering diabetes-induced vascular complications commonly seen in patients undergoing coronary artery bypass graft surgery (CABG). KATP subunits were detected in HIMA segments using Western blot and immunohistochemistry analyses. An organ bath system was used to interrogate endothelium-independent vasorelaxation caused by pinacidil. In pharmacological experiments, pinacidil was able to relax HIMA from patients with T2DM, with sensitivity comparable to our previous results. All three KATP subunits (SUR2B, Kir6.1 and Kir6.2) were observed in HIMA from patients with and without T2DM. There were no differences in the expression of the SUR2B subunit. The expression of the Kir6.1 subunit was lower in HIMA from T2DM patients. In the same group, the expression of the Kir6.2 subunit was higher. Therefore, KATP channels might not be the only method of pinacidil-induced dilatation of T2DM HIMA. T2DM may decrease the level of Kir6.1, a dominant subunit in VSM of HIMA, altering the interaction between pinacidil and those channels.