Expression and role of lumican in acute aortic dissection: A human and mouse study.

INTRODUCTION: Aortic dissection (AD) is a life-threatening emergency, and lumican (LUM) is a potential Biomarker for AD diagnosis. We investigated LUM expression patterns in patients with AD and explored the molecular functions of Lum in AD mice model. METHODS: LUM expression patterns were analyzed using aortic tissues of AD patients, and serum soluble LUM (s-LUM) levels were compared between patients with acute AD (AAD) and chronic AD (CAD). Lum-knockout (Lum-/-) mice were challenged with ß-aminopropionitrile (BAPN) and angiotensin II (Ang II) to induce AD. The survival rate, AD incidence, and aortic aneurysm (AA) in these mice were compared with those in BAPN-Ang II-challenged wildtype (WT) mice. Tgf-ß/Smad2, Mmps, Lum, and Nox expression patterns were examined. RESULTS: LUM expression was detected in the intima and media of the ascending aorta in patients with AAD. Serum s-LUM levels were significantly higher in patients with AAD than CAD. Furthermore, AD-associated mortality and thoracic aortic rupture incidence were significantly higher in the Lum-/- AD mice than in the WT AD mice. However, no significant pathologic changes in AA were observed in the Lum-/- AD mice compared with the WT AD mice. The BAPN-Ang II-challenged WT and Lum-/- AD mice had higher Tgf-ß, p-Smad2, Mmp2, Mmp9, and Nox4 levels than those of non-AD mice. We also found that Lum expression was significantly higher in the BAPN-Ang II-challenged WT in comparison to the unchallenged WT mice. CONCLUSION: LUM expression was altered in patients with AD display increased s-LUM in blood, and Lum-/- mice exhibited augmented AD pathogenesis. These findings support the notion that LUM is a biomarker signifying the pathogenesis of injured aorta seen in AAD. The presence of LUM is essential for maintenance of connective tissue integrity. Future studies should elucidate the mechanisms underlying LUM association in aortic changes.

Level of serum soluble lumican and risks of perioperative complications in patients receiving aortic surgery.

OBJECTIVE: Several serum biomarkers have been investigated for their potential as diagnostic tools in aortic disease; however, no study has investigated the association between serum biomarkers and outcomes after aortic surgery. This study explored the predictive ability of serum soluble lumican in postoperative outcomes after aortic surgery. METHODS: In total, 58 patients receiving aortic surgery for aortic dissection or aneurysm at Linkou Chang Gung Memorial Hospital in Taiwan in December 2011-September 2018 were enrolled. Blood samples were collected immediately upon patients' arrival in the intensive care unit after aortic surgery. The diagnostic properties of soluble lumican levels were assessed by performing receiver operating characteristic (ROC) curve analysis. The confidence interval (CI) of the area under the ROC curve (AUC) was measured using DeLong's nonparametric method and the optimal cutoff was determined using the Youden index. RESULTS: The serum soluble lumican level distinguished prolonged ventilation (AUC, 73.5%; 95% CI, 57.7%-89.3%) and hospital stay for >30 days (AUC, 78.2%; 95% CI, 61.6%-94.7%). The optimal cutoffs of prolonged ventilation and hospital stay for >30 days were 1.547 and 5.992 ng/mL, respectively. The sensitivity and specificity were respectively 100% (95% CI, 71.5%-100%) and 40.4% (95% CI, 26.4%-55.7%) for prolonged ventilation and 58% (95% 27.7%-84.8%) and 91.3% (95% CI, 79.2%-97.6%) for hospital stay for >30 days. CONCLUSIONS: The serum soluble lumican level can be a potential prognostic factor for predicting poor postoperative outcomes after aortic surgery. However, more studies are warranted in the future.

Endocan and Lumican in Relation to Cardiometabolic Risk in a Pediatric Overweight and Obese Cohort: A Cross-Sectional Study.

The aim of the study was to evaluate serum Endocan and Lumican levels as biomarkers for pediatric Nonalcoholic Fatty Liver Disease (NAFLD) and to explore their associations with pediatric cardiometabolic risk factors. We conducted a cross-sectional study on 68 pediatric obese and overweight (O&O) patients. Ten healthy controls were recruited. Serum Lumican and Endocan levels were analyzed using ELISA kits. O&O patients had lower levels of Endocan compared to healthy controls (p < 0.001). There were no differences between serum Endocan levels in O&O patients with NAFLD and those without (p = 0.53). Patients considered having Nonalcoholic Steatohepatitis (NASH) had lower Endocan levels compared to O&O patients without NASH (p = 0.026). Patients with metabolic syndrome had lower levels of Endocan (p = 0.003). There were no significant differences between serum Lumican levels in O&O children compared to healthy controls. Lumican levels were higher in patients with hypertension (p = 0.04). In O&O patients, Lumican levels were negatively correlated with Endocan levels (r = -0.37, p = 0.002). Endocan seems a promising biomarker for the evaluation of pediatric NASH. Lumican was not confirmed as a biomarker for NAFLD in our cohort but was associated with higher arterial pressure. Low Endocan levels are accompanied by high serum Lumican levels, and this could be an early signature of cardiometabolic risk.

Altered expression of small leucine-rich proteoglycans (Decorin, Biglycan and Lumican): Plausible diagnostic marker in urothelial carcinoma of bladder.

Small leucine-rich proteoglycans are components of extracellular matrix that regulates neoplastic transformation. Among small leucine rich proteoglycans, Decorin, Biglycan and Lumican are most commonly implicated markers, and their expression is well studied in various malignancies. In this novel study, we have collectively evaluated expression of these three molecules in urothelial carcinoma of bladder. Thirty patients of confirmed untreated bladder cancer, 30 healthy controls for blood and 30 controls for adjacent non-tumour tissue were enrolled. Blood was collected from all subjects and tumour/adjacent normal tissue was obtained from the patients. Circulatory levels were estimated by enzyme-linked immunosorbent assay, relative messenger RNA expression by quantitative polymerase chain reaction and protein expression by immunohistochemistry and western-blotting. Circulatory levels of Biglycan (p = 0.0038) and Lumican (p < 0.0001) were significantly elevated, and that of Decorin (p < 0.0001) was significantly reduced in patients as compared with controls. Protein expression by immunohistochemistry and western-blotting showed elevated expression of Lumican and Biglycan and lower expression of Decorin in urothelial carcinoma of bladder. Quantitative polymerase chain reaction for messenger RNA expression from tissue specimens revealed significantly higher expression of Biglycan (p = 0.0008) and Lumican (p = 0.01) and lower expression of Decorin (p < 0.0001) in urothelial carcinoma of bladder. Out of all molecules receiver operating characteristic curve showed that the 0.207 ng/ml cut-off of serum Lumican provided optimum sensitivity (90.0%) and specificity (90.0%). Significant alteration of matrix small leucine-rich proteoglycans in urothelial carcinoma of bladder was observed. Higher expression of Lumican in Bladder cancer patients with the cut-off value of highest optimum sensitivity and specificity shows its importance as a potential non-invasive marker for early detection of UBC following further validation in large patient cohort.

Identifying nonalcoholic fatty liver disease patients with active fibrosis by measuring extracellular matrix remodeling rates in tissue and blood.

Excess collagen synthesis (fibrogenesis) in the liver plays a causal role in the progression of nonalcoholic fatty liver disease (NAFLD). Methods are needed to identify patients with more rapidly progressing disease and to demonstrate early response to treatment. We describe here a novel method to quantify hepatic fibrogenesis flux rates both directly in liver tissue and noninvasively in blood. Twenty-one patients with suspected NAFLD ingested heavy water (2 H2 O, 50-mL aliquots) two to three times daily for 3-5 weeks prior to a clinically indicated liver biopsy. Liver collagen fractional synthesis rate (FSR) and plasma lumican FSR were measured based on 2 H labeling using tandem mass spectrometry. Patients were classified by histology for fibrosis stage (F0-F4) and as having nonalcoholic fatty liver or nonalcoholic steatohepatitis (NASH). Magnetic resonance elastography measurements of liver stiffness were also performed. Hepatic collagen FSR in NAFLD increased with advancing disease stage (e.g., higher in NASH than nonalcoholic fatty liver, positive correlation with fibrosis score and liver stiffness) and correlated with hemoglobin A1C. In addition, plasma lumican FSR demonstrated a significant correlation with hepatic collagen FSR. CONCLUSION: Using a well-characterized cohort of patients with biopsy-proven NAFLD, this study demonstrates that hepatic scar in NASH is actively remodeled even in advanced fibrosis, a disease that is generally regarded as static and slowly progressive. Moreover, hepatic collagen FSR correlates with established risks for fibrotic disease progression in NASH, and plasma lumican FSR correlates with hepatic collagen FSR, suggesting applications as direct or surrogate markers, respectively, of hepatic fibrogenesis in humans. (Hepatology 2017;65:78-88).