RESUMEN
The ß-catenin dependent canonical Wnt signaling pathway plays a crucial role in maintaining normal homeostasis. However, when dysregulated, Wnt signaling is closely associated with various pathological conditions, including inflammation and different types of cancer.Here, we show a new connection between the leukocyte inflammatory response and the Wnt signaling pathway. Specifically, we demonstrate that circulating human primary monocytes express distinct Wnt signaling components and are susceptible to stimulation by the classical Wnt ligand-Wnt-3a. Although this stimulation increased the levels of ß-catenin protein, the expression of the classical Wnt-target genes was not affected. Intriguingly, treating circulating human monocytes with Wnt-3a induces the secretion of cytokines and chemokines, enhancing monocyte migration. Mechanistically, the enhanced monocyte migration in response to Wnt stimuli is mediated through CCL2, a strong monocyte-chemoattractant.To further explore the physiological relevance of these findings, we conducted ex-vivo experiments using blood samples of patients with rheumatic joint diseases (RJD) - conditions where monocytes are known to be dysfunctional. Wnt-3a generated a unique cytokine expression profile, which was significantly distinct from that observed in monocytes obtained from healthy donors.Thus, our results provide the first evidence that Wnt-3a may serve as a potent stimulator of monocyte-driven immune processes. These findings contribute to our understanding of inflammatory diseases and, more importantly, shed light on the role of a core signaling pathway in the circulation.
Asunto(s)
Monocitos , Vía de Señalización Wnt , Humanos , Monocitos/metabolismo , Proteína Wnt3A/genética , Movimiento Celular , Quimiocinas , beta Catenina/metabolismoRESUMEN
AIMS: We examined whether thickness of the basal muscular interventricular septum (IVS), as measured by pre-procedural computed tomography (CT), could be used to identify the risk of conduction disturbances following transcatheter aortic valve replacement (TAVR). The IVS is a pivotal region of the electrical conduction system of the heart where the atrioventricular conduction axis is located. METHODS AND RESULTS: Included were 78 patients with severe aortic stenosis who underwent CT imaging prior to TAVR. The thickness of muscular IVS was measured in the coronal view, in systolic phases, at 1, 2, 5, and 10â mm below the membranous septum (MS). The primary endpoint was a composite of conduction disturbance following TAVR. Conduction disturbances occurred in 24 out of 78 patients (30.8%). Those with conduction disturbances were significantly more likely to have a thinner IVS than those without conduction disturbances at every measured IVS level (2.98 ± 0.52â mm vs. 3.38 ± 0.52â mm, 4.10 ± 1.02â mm vs. 4.65 ± 0.78â mm, 6.11 ± 1.12â mm vs. 6.88 ± 1.03â mm, and 9.72 ± 1.95â mm vs. 10.70 ± 1.55â mm for 1, 2, 5 and 10â mm below MS, respectively, P < 0.05 for all). Multivariable logistic regression analysis showed that pre-procedural IVS thickness (<4â mm at 2â mm below the MS) was a significant independent predictor of post-procedural conduction disturbance (adjOR 7.387, 95% CI: 2.003-27.244, P = 0.003). CONCLUSION: Pre-procedural CT assessment of basal IVS thickness is a novel predictive marker for the risk of conduction disturbances following TAVR. The IVS thickness potentially acts as an anatomical barrier protecting the underlying conduction system from mechanical compression during TAVR.
Asunto(s)
Estenosis de la Válvula Aórtica , Reemplazo de la Válvula Aórtica Transcatéter , Tabique Interventricular , Humanos , Masculino , Femenino , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Estenosis de la Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Tabique Interventricular/diagnóstico por imagen , Anciano de 80 o más Años , Factores de Riesgo , Anciano , Arritmias Cardíacas/etiología , Arritmias Cardíacas/fisiopatología , Arritmias Cardíacas/diagnóstico por imagen , Sistema de Conducción Cardíaco/fisiopatología , Sistema de Conducción Cardíaco/diagnóstico por imagen , Resultado del Tratamiento , Valor Predictivo de las Pruebas , Medición de Riesgo , Índice de Severidad de la Enfermedad , Estudios Retrospectivos , Válvula Aórtica/cirugía , Válvula Aórtica/diagnóstico por imagen , Tomografía Computarizada Multidetector , Tomografía Computarizada por Rayos X , Potenciales de AcciónRESUMEN
BACKGROUND : Clinically significant post-endoscopic bleeding (CSPEB) is a common complication following colonic endoscopic mucosal resection (EMR). Current prediction tools are clinical and do not use the appearance of the post-EMR mucosal defect. We aimed to predict CSPEB by analyzing blood vessel morphology within the post-EMR mucosal defect. METHODS : 43 patients with CSPEB were matched to 43 non-bleeders for clinical variables associated with CSPEB. Computerized image analysis quantified the morphologic characteristics of the blood vessels in the defect. Variables were measured in relation to the mucosal defect area. Multivariate analysis and a neural network (NNET) were used as prediction models. RESULTS : The CSPEB group vessels had larger maximum diameter (113.07 vs. 69.03; Pâ<â0.001), larger minimum radius (5.09 vs. 3.28; Pâ=â0.002), larger perimeter value (337.82 vs. 193.86; Pâ<â0.001), larger vessel length-of-outline (351.83 vs. 220.68; Pâ=â0.002), and larger fractal dimension (1.11 vs. 1.10; Pâ=â0.005) compared with non-bleeders. Discriminant analysis yielded 86â% sensitivity and 76.7â% specificity and an NNET classifier yielded 100â% sensitivity and 76.9â% specificity for identifying patients at risk. CONCLUSIONS : Blood vessel morphology in the post-EMR defect can be used to predict bleeding following colonic EMR.