Carbamylated low-density lipoprotein induces endothelial dysfunction

Aims Cardiovascular events remain the leading cause of death in Western world. Atherosclerosis is the most common underlying complication driven by low-density lipoproteins (LDL) disturbing vascular integrity. Carbamylation of lysine residues, occurring primarily in the presence of chronic kidney disease (CKD), may affect functional properties of lipoproteins; however, its effect on endothelial function is unknown. Methods and results Low-density lipoprotein from healthy donors was isolated and carbamylated. Vascular reactivity after treatment with native LDL (nLDL) or carbamylated LDL (cLDL) was examined in organ chambers for isometric tension recording using aortic rings of wild-type or lectin-like-oxidized LDL receptor-1 (LOX-1) transgenic mice. Reactive oxygen species (ROS) and nitric oxide (NO) production were determined using electron spin resonance spectroscopy. The effect of LDL-carbamyl-lysine levels on cardiovascular outcomes was determined in patients with CKD during a median follow-up of 4.7 years. Carbamylated LDL impaired endothelium-dependent relaxation to acetylcholine or calcium-ionophore A23187, but not endothelium-independent relaxation to sodium nitroprusside. In contrast, nLDL had no effect. Carbamylated LDL enhanced aortic ROS production by activating NADPH-oxidase. Carbamylated LDL stimulated endothelial NO synthase (eNOS) uncoupling at least partially by promoting S-glutathionylation of eNOS. Carbamylated LDL-induced endothelial dysfunction was enhanced in LOX-1 transgenic mice. In patients with CKD, LDL-carbamyl-lysine levels were significant predictors for cardiovascular events and all-cause mortality. Conclusions Carbamylation of LDL induces endothelial dysfunction via LOX-1 activation and increased ROS production leading to eNOS uncoupling. This indicates a novel mechanism in the pathogenesis of atherosclerotic disease which may be pathogenic and prognostic in patients with CKD and high plasma levels of cLD

Plant lectins: the ties that bind in root symbiosis and plant defense

Lectins are a diverse group of carbohydrate-binding proteins that are found within and associated with organisms from all kingdoms of life. Several different classes of plant lectins serve a diverse array of functions. The most prominent of these include participation in plant defense against predators and pathogens and involvement in symbiotic interactions between host plants and symbiotic microbes, including mycorrhizal fungi and nitrogen-fixing rhizobia. Extensive biological, biochemical, and molecular studies have shed light on the functions of plant lectins, and a plethora of uncharacterized lectin genes are being revealed at the genomic scale, suggesting unexplored and novel diversity in plant lectin structure and function. Integration of the results from these different types of research is beginning to yield a more detailed understanding of the function of lectins in symbiosis, defense, and plant biology in general

Carbamylated low-density lipoprotein induces endothelial dysfunction

AIMS: Cardiovascular events remain the leading cause of death in Western world. Atherosclerosis is the most common underlying complication driven by low-density lipoproteins (LDL) disturbing vascular integrity. Carbamylation of lysine residues, occurring primarily in the presence of chronic kidney disease (CKD), may affect functional properties of lipoproteins; however, its effect on endothelial function is unknown. METHODS AND RESULTS: Low-density lipoprotein from healthy donors was isolated and carbamylated. Vascular reactivity after treatment with native LDL (nLDL) or carbamylated LDL (cLDL) was examined in organ chambers for isometric tension recording using aortic rings of wild-type or lectin-like-oxidized LDL receptor-1 (LOX-1) transgenic mice. Reactive oxygen species (ROS) and nitric oxide (NO) production were determined using electron spin resonance spectroscopy. The effect of LDL-carbamyl-lysine levels on cardiovascular outcomes was determined in patients with CKD during a median follow-up of 4.7 years. Carbamylated LDL impaired endothelium-dependent relaxation to acetylcholine or calcium-ionophore A23187, but not endothelium-independent relaxation to sodium nitroprusside. In contrast, nLDL had no effect. Carbamylated LDL enhanced aortic ROS production by activating NADPH-oxidase. Carbamylated LDL stimulated endothelial NO synthase (eNOS) uncoupling at least partially by promoting S-glutathionylation of eNOS. Carbamylated LDL-induced endothelial dysfunction was enhanced in LOX-1 transgenic mice. In patients with CKD, LDL-carbamyl-lysine levels were significant predictors for cardiovascular events and all-cause mortality. CONCLUSIONS: Carbamylation of LDL induces endothelial dysfunction via LOX-1 activation and increased ROS production leading to eNOS uncoupling. This indicates a novel mechanism in the pathogenesis of atherosclerotic disease which may be pathogenic and prognostic in patients with CKD and high plasma levels of cLDL

Assessment of ecosystem integrity and service gradients across Europe using the LTER Europe network

Better integration of knowledge from ecological, social and economic science is necessary to advance the understanding and modelling of socio-ecological systems. To model ecosystem integrity (EI) and ecosystem services (ES) at the landscape scale, assessment matrices are commonly used. These matrices assign capacities to provide different services to different land cover types. We revised such an existing matrix and examined the regional heterogeneity in EI and ES provision in Europe and searched for spatial gradients in their provision to elucidate their suitability for large-scale EI and ES mapping in Europe. Overall, 28 sites belonging to the Long-Term Ecological Research network in Europe participated in this study, covering a longitudinal gradient from Spain to Bulgaria and a latitudinal gradient from Italy to Sweden. As a primary outcome, an improved and consolidated EI and ES matrix was achieved with 17.5% of all matrix fields updated. For the first time, this new matrix also contains measures of uncertainty for each entry. EI and ES provision assessments were more variable for natural and semi-natural than for more anthropogenically dominated land cover classes. Among the main types of EI and ES, cultural service provision was rated most heterogeneously in Europe, while abiotic provisioning services were more constant. Longitudinal and latitudinal EI and ES gradients were mostly detected in natural and semi-natural land cover types where temperature and precipitation are major drivers. In anthropogenically determined systems in which cultural services play a dominant role, temperature and precipitation gradients were less important. Our results suggest that this matrix approach to assess EI and ES provision principally works on broad spatial scales; however, local assessments for natural systems seem to be less generalizable than assessments from anthropogenically determined systemsVytauto Didžiojo universitetasŽemės ūkio akademij

One-to-one coupling of glacial climate variability in Greenland and Antarctica

Precise knowledge of the phase relationship between climate changes in the two hemispheres is a key for understanding the Earth's climate dynamics. For the last glacial period, ice core studies1, 2 have revealed strong coupling of the largest millennial-scale warm events in Antarctica with the longest Dansgaard–Oeschger events in Greenland3, 4, 5 through the Atlantic meridional overturning circulation6, 7, 8. It has been unclear, however, whether the shorter Dansgaard–Oeschger events have counterparts in the shorter and less prominent Antarctic temperature variations, and whether these events are linked by the same mechanism. Here we present a glacial climate record derived from an ice core from Dronning Maud Land, Antarctica, which represents South Atlantic climate at a resolution comparable with the Greenland ice core records. After methane synchronization with an ice core from North Greenland9, the oxygen isotope record from the Dronning Maud Land ice core shows a one-to-one coupling between all Antarctic warm events and Greenland Dansgaard–Oeschger events by the bipolar seesaw6. The amplitude of the Antarctic warm events is found to be linearly dependent on the duration of the concurrent stadial in the North, suggesting that they all result from a similar reduction in the meridional overturning circulation