Atherosclerosis, a deadly disease insufficiently addressed by cholesterol-lowering drugs, needs new therapeutic strategies. Fortilin, a 172-amino acid multifunctional polypeptide, binds p53 and blocks its transcriptional activation of Bax, thereby exerting potent antiapoptotic activity. Although fortilin-overexpressing mice reportedly exhibit hypertension and accelerated atherosclerosis, it remains unknown if fortilin, not hypertension, facilitates atherosclerosis. Our objective was to test the hypothesis that fortilin in and of itself facilitates atherosclerosis by protecting macrophages against apoptosis. We generated fortilin-deficient ( fortilin+/−) mice and wild-type counterparts ( fortilin+/+) on a LDL receptor ( Ldlr)−/− apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 ( Apobec1)−/− hypercholesterolemic genetic background, incubated them for 10 mo on a normal chow diet, and assessed the degree and extent of atherosclerosis. Despite similar blood pressure and lipid profiles, fortilin+/− mice exhibited significantly less atherosclerosis in their aortae than their fortilin +/+ littermate controls. Quantitative immunostaining and flow cytometry analyses showed that the atherosclerotic lesions of fortilin+/− mice contained fewer macrophages than those of fortilin+/+ mice. In addition, there were more apoptotic cells in the intima of fortilin+/− mice than in the intima of fortilin+/+ mice. Furthermore, peritoneal macrophages from fortilin+/− mice expressed more Bax and underwent increased apoptosis, both at the baseline level and in response to oxidized LDL. Finally, hypercholesterolemic sera from Ldlr−/− Apobec1−/− mice induced fortilin in peritoneal macrophages more robustly than sera from control mice. In conclusion, fortilin, induced in the proatherosclerotic microenvironment in macrophages, protects macrophages against Bax-induced apoptosis, allows them to propagate, and accelerates atherosclerosis. Anti-fortilin therapy thus may represent a promising next generation antiatherosclerotic therapeutic strategy.

Severe TR was a significant predictor of long-term mortality rate in PAH, and TR severity correlated with PAH severity.

Human activity is rapidly increasing the radiance and geographic extent of artificial light at night (ALAN) leading to alterations in the development, behavior, and physiological state of many organisms. A limited number of community-scale studies investigating the effects of ALAN have allowed for spatial aggregation through positive phototaxis, the commonly observed phenomenon of arthropod movement toward light. We performed an open field study (without restricted arthropod access) to determine the effects of ALAN on local arthropod community composition, plant traits, and local herbivory and predation rates. We found strong positive phototaxis in 10 orders of arthropods, with increased (159% higher) overall arthropod abundance under ALAN compared to unlit controls. The arthropod community under ALAN was more diverse and contained a higher proportion of predaceous arthropods (15% vs 8%). Predation of immobilized flies occurred 3.6 times faster under ALAN; this effect was not observed during the day. Contrary to expectations, we also observed a 6% increase in herbivory under ALAN. Our results highlight the importance of open experimental field studies in determining community-level effects of ALAN.

No abstract

No abstract