ABSTRACT
The integrity of blood vessels controls vascular permeability and extravasation of blood cells, across the endothelium. Thus, the impairment of endothelial integrity leads to hemorrhage, edema, and inflammatory infiltration. However, the molecular mechanism underlying vascular integrity has not been fully understood. Here, we demonstrate an essential role for A-kinase anchoring protein 12 (AKAP12) in the maintenance of endothelial integrity during vascular development. Zebrafish embryos depleted of akap12 (akap12 morphants) exhibited severe hemorrhages. In vivo time-lapse analyses suggested that disorganized interendothelial cell-cell adhesions in akap12 morphants might be the cause of hemorrhage. To clarify the molecular mechanism by which the cell-cell adhesions are impaired, we examined the cell-cell adhesion molecules and their regulators using cultured endothelial cells. The expression of PAK2, an actin cytoskeletal regulator, and AF6, a connector of intercellular adhesion molecules and actin cytoskeleton, was reduced in AKAP12-depleted cells. Depletion of either PAK2 or AF6 phenocopied AKAP12-depleted cells, suggesting the reduction of PAK2 and AF6 results in the loosening of intercellular junctions. Consistent with this, overexpression of PAK2 and AF6 rescued the abnormal hemorrhage in akap12 morphants. We conclude that AKAP12 is essential for integrity of endothelium by maintaining the expression of PAK2 and AF6 during vascular development.
Subject(s)
Animals , Humans , A Kinase Anchor Proteins/genetics , Blood Vessels/abnormalities , Cell Cycle Proteins/genetics , Down-Regulation , Embryo, Nonmammalian/abnormalities , Gene Deletion , Gene Expression Regulation, Developmental , Hemorrhage/embryology , Human Umbilical Vein Endothelial Cells , Intercellular Junctions/genetics , Kinesins/genetics , Myosins/genetics , Zebrafish/embryology , p21-Activated Kinases/geneticsABSTRACT
Se realiza un estudio longitudenal restrospectivo con el objeto de determinar la tasa de mortalidad materna en el IMNA de La Paz. Revisando los libros de archivo y partes diarios de atenciòn se obtiene el nùmero total de defunciones maternas, partos, cesàreasy recien nacidos vivos entre 1981 a 1990. Relacionando el nùmero de muertes maternas con el nùmero total de recièn nacidos vivos, encontramos una tasa de mortalidad materna de 28o/ooo. Se señalan tambièn las diferentes patologias que ocasionaron el deceso, concluyendose las Toxemias y la Eclampsia, luego estàn las Hemorragias e Infecciones. Se concluye remarcando la disminuciòn de la mortalidad materna, con respecto a la anterior dècada, haciendo alguna consideraciones que expliquen este hecho