Abcc6 deficiency causes increased infarct size and apoptosis in a mouse cardiac ischemia-reperfusion model.

ABCC6 genetic deficiency underlies pseudoxanthoma elasticum (PXE) in humans, characterized by ectopic calcification, and early cardiac disease. The spectrum of PXE has been noted in Abcc6-deficient mice, including dystrophic cardiac calcification. We tested the role of Abcc6 in response to cardiac ischemia-reperfusion (I/R) injury. To determine the role of Abcc6 in cardioprotection, we induced ischemic injury in mice in vivo by occluding the left anterior descending artery (30 minutes) followed by reperfusion (48 hours). Infarct size was increased in Abcc6-deficient mice compared with wild-type controls. Additionally, an Abcc6 transgene significantly reduced infarct size on the background of a naturally occurring Abcc6 deficiency. There were no differences in cardiac calcification following I/R, but increased cardiac apoptosis was noted in Abcc6-deficient mice. Previous studies have implicated the bone morphogenetic protein (BMP) signaling pathway in directing calcification, and here we showed that the BMP responsive transcription factors pSmad1/5/8 were increased in hearts of Abcc6 mice. Consistent with this finding, BMP4 and BMP9 were increased and activin receptor-like kinase-2 and endoglin were downregulated in cardiac extracts from Abcc6-deficient mice versus controls. These data identify Abcc6 as a novel modulator of cardiac myocyte survival after I/R. This cardioprotective mechanism may involve inhibition of the BMP signaling pathway, which modulates apoptosi

Ecological and evolutionary significance of dispersal by freshwater invertebrates

Traditional expectations for how widely and how often freshwater invertebrates disperse differ from empirical data. Freshwater invertebrates have been characterized as frequent, widespread dispersers, particularly those that are transported passively. Our review finds that this characterization may describe the potential for dispersal in some taxa, but it is not an accurate generalization for actual dispersal rates. High variance among habitats and taxonomic groups is a consistent theme. Advances in population genetics may help resolve these issues, but underlying assumptions should be carefully tested. Further, even unbiased estimates of gene flow may not equate with individual movement, because not all dispersers survive and reproduce. Some freshwater invertebrates may exist in classic Levins metapopulations. However, other species fit into a broader metapopulation definition, where temporal dispersal via diapause is functionally equivalent to spatial dispersal. In the latter case, local extinctions and rescue effects may be rare or absent. Finally, limited dispersal rates in many taxa suggest that theories of freshwater community assembly and structure can be made more robust by integrating dispersal and local processes as joint, contingent regulators. Recent research on freshwater invertebrate dispersal has substantially advanced our basic and applied understanding of freshwaters, as well as evolutionary ecology in general