Abstract Numerous recent studies have shown that in the continuum of cardiovascular diseases, the measurement of arterial stiffness has powerful predictive value in cardiovascular risk and mortality and that this value is independent of other conventional risk factors, such as age, cholesterol levels, diabetes, smoking, or average blood pressure. Vascular stiffening is often the main cause of arterial hypertension (AHT), which is common in the presence of obesity. However, the mechanisms leading to vascular stiffening, as well as preventive factors, remain unclear. The aim of the present study was to investigate the consequences of apelin deficiency on the vascular stiffening and wall remodeling of aorta in mice. This factor freed by visceral adipose tissue, is known for its homeostasic role in lipid and vascular metabolisms, or again in inflammation. We compared the level of metabolic markers, inflammation of white adipose tissue (WAT), and aortic wall remodeling from functional and structural approaches in apelin-deficient and wild-type (WT) mice. Apelin-deficient mice were generated by knockout of the apelin gene (APL-KO). From 8 mice by groups, aortic stiffness was analyzed by pulse wave velocity measurements and by characterizations of collagen and elastic fibers. Mann–Whitney statistical test determined the significant data (p < 5%) between groups. The APL-KO mice developed inflammation, which was associated with significant remodeling of visceral WAT, such as neutrophil elastase and cathepsin S expressions. In vitro, cathepsin S activity was detected in conditioned medium prepared from adipose tissue of the APL-KO mice, and cathepsin S activity induced high fragmentations of elastic fiber of wild-type aorta, suggesting that the WAT secretome could play a major role in vascular stiffening. In vivo, remodeling of the extracellular matrix (ECM), such as collagen accumulation and elastolysis, was observed in the aortic walls of the APL-KO mice, with the latter associated with high cathepsin S activity. In addition, pulse wave velocity (PWV) and AHT were increased in the APL-KO mice. The latter could explain aortic wall remodeling in the APL-KO mice. The absence of apelin expression, particularly in WAT, modified the adipocyte secretome and facilitated remodeling of the ECM of the aortic wall. Thus, elastolysis of elastic fibers and collagen accumulation contributed to vascular stiffening and AHT. Therefore, apelin expression could be a major element to preserve vascular homeostasis.
Triple-negative breast carcinoma (TN) is a heterogeneous cancer type expressing EGFR in 75% of cases. MUC1 is a large type I sialylated glycoprotein comprising two subunits (α and β chains, also called respectively MUC1-VNTR and MUC1-CT), which was found to regulate EGFR activity through endocytic internalisation. Endocytosis and autophagy use the lysosome pathway involving NEU1. Recently, a molecular EGFR-MUC1-NEU1 complex was suggested to play a role in EGFR pathway. In the aim to understand the relationship between EGFR-MUC1-NEU1 complex and autophagy in breast carcinoma, we compared triple negative (TN) showing a high-EGFR expression with luminal (LUM) presenting low-EGFR level. We studied the expression of MUC1-VNTR, MUC1-CT and NEU1 in comparison with those of two molecular actors of autophagy, PI3K (p110β) and Beclin1. A total of 87 breast cancers were split in two groups following the immunohistochemical classification of breast carcinoma: 48 TN and 39 LUM. Our results showed that TN presented a high expression of EGFR and a low expression of MUC1-VNTR, MUC1-CT, NEU1, Beclin-1 and PI3Kp110β. Moreover, in TN, a positive statistical correlation was observed between Beclin-1 or PI3Kp110β and MUC1-VNTR or NEU1, but not with EGFR. In conclusion, our data suggest that autophagy is reduced in TN leading likely to the deregulation of EGFR-MUC1-NEU1 complex and its associated cellular pathways.
Background: Although liquid-based cytology (LBC) is now recommended for cervical cancer screening, it requires expensive automated devices and materials.To evaluate the efficiency of inexpensive LBC methods relying on an inexpensive fixative liquid, Easyfix ® , we compared the results obtained by the liquid-based cytology (LBC) diagnoses performed by cytocentrifugations (Papspin ® and Turbitec ® ) with those obtained by histology.Furthermore, we evaluated the efficiency of the fixative liquid, Easyfix ® , to preserve HPV DNA in the collected samples.Method: 266 LBC were compared with 174 colposcopies and 91 Loop Electrosurgical Excision Procedure (LEEP).Among the LBC, 51 were performed using the Papspin ® system and 215 were performed using the Turbitec ® system.To control the quality of the preservation liquid, Easyfix ® , we correlated the results of HCII assays with those of HPV PCR.Results: For Papspin ® and Turbitec ® systems, the sensitivities were respectively 82.6% (95% CI: 61.2-95.0%,p < 0.001) and 75.0%(95% CI: 64.4-89.8%,p < 0.001) and the specificities were 92.6% (95%CI: 76.5-99.1%,p < 0.001) and 96.2% (95% CI: 91.3-98.7%,p < 0.001).We find no statistical difference between the results of the both systems (p = ns).The sensitivity of the HCII was 86.4% (95% IC: 77.4-92.8%,p < 0.001) and the specificity was 39.4% (95% CI: 31.2-48.1%,p < 0.001).The comparison between HCII and HPV-PCR shows a good correlation: the kappa was 0.89. Conclusion:LBC performed by cytocentrifugations are inexpensive, reduce inadequate smears, show excellent efficiency and allow HPV detection by molecular biology.
