RESUMEN
BACKGROUND: Cell homing is the mechanism by which an injury releases signaling molecules that cause recruitment, proliferation, migration and differentiation of progenitor cells. Stromal derived factor-1 (SDF-1) and its receptor CXCR4 are key molecules involved in homing and little is known about their activation in cardiopathies. Here, we assessed the homing activation status of bone marrow cells (BMC) concerning the SDF-1 and CXCR4 expression in ischemic (IHD) and valvular (VHD) heart diseases. METHODS: The SDF-1 and inflammatory profile were analyzed by ELISA from plasma obtained bone marrow of ischemic heart patients (IHD, n = 41), valvular heart patients (VHD, n = 30) and healthy controls (C, n = 9). Flow cytometry was used to evaluate CXCR4 (CD184) expression on the surface of bone marrow cells, and the CXCR4 expression was estimated by real-time quantitative PCR. RESULTS: The SDF-1 levels in the groups IHD, VHD and control were, respectively, 230, 530 and 620 pg/mL (P = 0.483), and was decreased in VHD patients using beta-blockers (263 pg/mL) when compared with other (844 pg/mL) (P = 0.023). Compared with IHD, the VHD group showed higher CXCR4 (P = 0.071) and CXCR7 (P = 0.082) mRNA expression although no difference in the level of CXCR4+ bone marrow cells was found between groups (P = 0.360). CONCLUSION: In conclusion, pathophysiological differences between IHD and VHD can affect the molecules involved in the activation of homing. In addition, the use of beta-blockers appears to interfere in this mechanism, a fact that should be considered in protocols that use BMC.
Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Células de la Médula Ósea/citología , Enfermedades de las Válvulas Cardíacas/terapia , Células Madre Mesenquimatosas/citología , Isquemia Miocárdica/terapia , Adulto , Anciano , Biomarcadores/metabolismo , Células de la Médula Ósea/metabolismo , Quimiocina CXCL12/metabolismo , Femenino , Enfermedades de las Válvulas Cardíacas/genética , Enfermedades de las Válvulas Cardíacas/patología , Humanos , Mediadores de Inflamación/metabolismo , Masculino , Células Madre Mesenquimatosas/metabolismo , Persona de Mediana Edad , Isquemia Miocárdica/genética , Isquemia Miocárdica/patología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores CXCR/genética , Receptores CXCR/metabolismo , Receptores CXCR4/genética , Receptores CXCR4/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
PURPOSE: Transcatheter arterial embolization (TAE) has been widely used in treating non-curative hepatocellular carcinoma (HCC). However, it is noticed that TAE may cause invasion of some cancer cells into circulation, resulting in distal metastasis and poor therapeutic outcome. Here, we aimed to reduce the side effects of TAE using the inhibitors for epidermal growth factor receptor (EGFR). METHODS: Transient hepatic artery ligation (HAL) was used as a mouse model for TAE. EGFR inhibitors were applied. Tumor size, presence of tumor cells in circulation, distal tumor formation, and activation of genes associated with tumor cell invasion and metastasis were analyzed. RESULTS: Inhibitors for EGFR significantly reduced the size of primary tumor, presence of tumor cells in circulation, and distal tumor formation after HAL. Further studies showed that EGFR inhibition suppressed several genes associated with tumor cell invasion and metastasis, such as vascular endothelial growth factor-A, stromal cell-derived factor 1, and Slug. CONCLUSION: EGFR inhibitor application may reduce circulating cancer cells during TAE and thus improve the therapy for advanced HCC.