Plasma Endocan Levels Research Articles

Endocan and Non-Dipping Circadian Pattern in Newly Diagnosed Essential Hypertension.

Background and ObjectivesNon-dipper hypertension is frequently accompanied by endothelial dysfunction and activation. Previous studies suggested that endocan may be a novel endothelial dysfunction marker. This study aims to investigate the association between circadian blood pressure (BP) pattern and plasma endocan levels together with high-sensitivity C-reactive protein (hsCRP) in patients with newly diagnosed untreated hypertension.Subjects and MethodsTwenty-four hour ambulatory blood pressure monitoring was recorded in 35 dipper, 35 non-dipper hypertensives and 35 healthy controls. Endocan levels were measured by enzyme-linked immunosorbent assay. Serum levels of hsCRP were also recorded.ResultsDespite similar daytime and 24-hour average BP values between dippers and non-dippers, statistically significant high nocturnal BP was accompanied by a non-dipping pattern (Systolic BP: 132±9 vs. 147±11 mmHg; Distolic BP: 80±7 vs. 91±9 mmHg, respectively, p<0.001 for both). Non-dipper patients demonstrated higher endocan levels compared to dippers and normotensives (367 (193-844) pg/mL, 254 (182-512) pg/mL and 237 (141-314) pg/ml, respectively, p<0.001). HsCRP levels were significantly higher in non-dippers than the other groups (p=0.013). In a multivariate logistic regression analysis, endocan (p=0.021) and hsCRP (p=0.044) were independently associated with a non-dipping pattern.ConclusionElevated endocan levels were found in non-dipper groups. Endocan and hsCRP were found to be independently associated with a non-dipping pattern. We suggest that elevated levels of endocan in non-dipper hypertensive patients might be associated with a longer duration of exposure to high BP. These results point to the possible future role of endocan in selection of hypertensive patients at higher risk or target organ damage.

0730. Plasma endocan levels are associated with endothelial dysfunction during experimental human endotoxemia

The endothelium plays a central role in pathophysiology of sepsis. Systemic inflammation results in endothelial dysfunction, contributing to the development of shock and multiple organ dysfunction. However, an easy to obtain, early, and clinically applicable marker of endothelial dysfunction is currently not available. Such a marker could guide early and targeted therapy such as selective iNOS inhibition. Endocan is a soluble proteoglycan secreted by endothelial cells in response to pro-inflammatory cytokines, bacterial endotoxins, and angiogenic factors, and enhances microvascular permeability. Plasma endocan levels are increased in septic patients, and have been shown to correlate with sepsis severity and mortality. However, the direct relationship between endocan and endothelial function has not yet been investigated in humans in vivo.

Plasma endocan levels associate with inflammation, vascular abnormalities, cardiovascular events, and survival in chronic kidney disease.

Plasma endocan levels are elevated in a large number of diseases, and may reflect endothelial cell dysfunction. There are currently no data on endocan in patients with chronic kidney disease (CKD). Therefore, we measured plasma endocan in 251 patients with CKD (stage 1-5) and 60 control individuals. Plasma endocan concentrations correlated with estimated glomerular filtration rate (eGFR), different markers of inflammation (pentraxin 3 and high-sensitivity C-reactive protein), and vascular abnormalities (flow-mediated vasodilation (FMV) and carotid intima media thickness (CIMT)). All-cause mortality and cardiovascular events (CVE) were also analyzed with respect to plasma endocan. Patients with CKD showed significantly increased plasma endocan (4.7 [IQR 1.9-9.4] compared with controls [IQR 1.1-1.5] ng/ml), with values progressively higher across stages of CKD. On univariate analysis, plasma endocan concentrations correlated negatively with eGFR and FMV, but positively with both markers of inflammation and CIMT. However, on multivariate analysis only high-sensitivity C-reactive protein, FMV, and CIMT remained significantly associated with plasma endocan. On Cox survival analysis, endocan levels were associated with all-cause mortality and CVE in these patients. Thus, plasma endocan increases in the presence of decreasing eGFR and influences all-cause mortality and CVE in patients with CKD independent of traditional and nontraditional risk factors.

Identification of a 14 kDa endocan fragment generated by cathepsin G, a novel circulating biomarker in patients with sepsis

Severe septic syndrome, which is the most prevalent and lethal cause of acute respiratory distress syndrome, remains one of the most frequent causes of admission and death in intensive care units (ICU). Inflammatory phenomenon leading to severe sepsis are multiple and not yet completely understood. The main target damage during severe sepsis is the endothelium. Endocan, specifically secreted by activated-pulmonary vascular endothelial cells, is thought to play a key role in the control of the lung inflammatory reaction. A recent clinical investigation found that a low plasma endocan level was predictive of respiratory failure. In this study, the hypothesis that low levels of endocan may result from proteolysis was tested. We demonstrate that cathepsin G (CG), neutrophil elastase (NE), and to a lesser extent proteinase 3 (PR3), degrade endocan. Interestingly, a novel endocan peptide fragment of 14kDa, named p14, was identified, resulting from the specific cleavage of endocan by CG, corresponding to the N-terminal 111–116 amino acids of the endocan polypeptide. An immunoassay specific for p14 endocan fragment was then developed, and revealed increased plasma levels of p14 in 20 out of 55 severe septic patients, ranging from 0.52 to 10.40ng/mL versus undetectable p14 in plasma from 32 control subjects (p=0.0011). No correlations were found between p14 and endocan blood levels in severe septic patients. Taken together, the p14 endocan fragment represents a novel interesting biomarker which could participate to the pathogenesis of sepsis.