Proteomic and transcriptomic analysis of heart failure due to volume overload in a rat aorto-caval fistula model provides support for new potential therapeutic targets - monoamine oxidase A and transglutaminase 2

<p>Abstract</p> <p>Background</p> <p>Chronic hemodynamic overloading leads to heart failure (HF) due to incompletely understood mechanisms. To gain deeper insight into the molecular pathophysiology of volume overload-induced HF and to identify potential markers and targets for novel therapies, we performed proteomic and mRNA expression analysis comparing myocardium from Wistar rats with HF induced by a chronic aorto-caval fistula (ACF) and sham-operated rats harvested at the advanced, decompensated stage of HF.</p> <p>Methods</p> <p>We analyzed control and failing myocardium employing iTRAQ labeling, two-dimensional peptide separation combining peptide IEF and nano-HPLC with MALDI-MS/MS. For the transcriptomic analysis we employed Illumina RatRef-12v1 Expression BeadChip.</p> <p>Results</p> <p>In the proteomic analysis we identified 2030 myocardial proteins, of which 66 proteins were differentially expressed. The mRNA expression analysis identified 851 differentially expressed mRNAs.</p> <p>Conclusions</p> <p>The differentially expressed proteins confirm a switch in the substrate preference from fatty acids to other sources in the failing heart. Failing hearts showed downregulation of the major calcium transporters SERCA2 and ryanodine receptor 2 and altered expression of creatine kinases. Decreased expression of two NADPH producing proteins suggests a decreased redox reserve. Overexpression of annexins supports their possible potential as HF biomarkers. Most importantly, among the most up-regulated proteins in ACF hearts were monoamine oxidase A and transglutaminase 2 that are both potential attractive targets of low molecular weight inhibitors in future HF therapy.</p

Valuable Secondary Habitats or Hazardous Ecological Traps? Environmental Risk Assessment of Minor and Trace Elements in Fly Ash Deposits across the Czech Republic

Deposits of coal combustion wastes, especially fly ash, are sources of environmental and health risks in industrial regions. Recently, fly ash deposits have been reported as habitat surrogates for some threatened arthropods in Central Europe. However, the potential environmental risks of fly ash have not yet been assessed in the region. We analysed concentrations of 19 minor and trace elements in 19 lignite combustion waste deposits in the Czech Republic. We assessed their environmental risks by comparison with the national and EU legislation limits, and with several commonly used indices. Over 50% of the samples exceeded the Czech national limits for As, Cu, V, or Zn, whilst only V exceeded the EU limits. For some studied elements, the high-risk indices were detected in several localities. Nevertheless, the measured water characteristics, the long-term presence of fly ash, previous leaching by acid rains, and the low amount of organic matter altogether can infer low biological availability of these elements. We presume the revealed high concentrations of some heavy metals at some studied sites can be harmful for some colonising species. Nevertheless, more ecotoxicological research on particular species is needed for final decision on their conservation potential for terrestrial and freshwater biota.info:eu-repo/semantics/publishedVersio

The Role of Renal Vascular Reactivity in the Development of Renal Dysfunction in Compensated and Decompensated Congestive Heart Failure

Background/Aims: Reduction of renal blood flow (RBF) is commonly thought to be a causative factor of renal dysfunction in congestive heart failure (CHF), but the exact mechanism of the renal hypoperfusion is not clear. Apart from the activation of neurohormonal systems controlling intrarenal vascular tone, the cause might be altered reactivity of the renal vasculature to endogenous vasoactive agents. Methods: To evaluate the role of this mechanism, we assessed by an ultrasonic transient-time flow probe maximum RBF responses to renal artery infusion of angiotensin II (ANG II), norepinephrine (NE) and acetylcholine (Ach) in healthy male rats and animals with compensated and decompensated CHF. CHF was induced by volume overload achieved by the creation of the aorto-caval fistula (ACF) in Hannover Sprague-Dawley rats. Results: Maximum responses in RBF to ANG II were similar in rats studied five weeks (compensated phase) and 20 weeks (decompensated phase) after ACF creation when compared to sham-operated rats. On the other hand, NE elicited larger maximum decreases in RBF in rats with CHF (five and 20 weeks post-ACF) than in sham-operated controls. We observed greater maximum vasodilatory responses to Ach only in rats with a compensated stage of CHF (five weeks post-ACF). Conclusion: Greater renal vasoconstrictor responsiveness to ANG II or reduced renal vasodilatation in response to Ach do not play a decisive role in the development of renal dysfunction in ACF rats with compensated and decompensated CHF. On the other hand, exaggerated renal vascular responsiveness to NE may be here a contributing causative factor, active in either CHF phase

The ecological role of permanent ponds in Europe: a review of dietary linkages to terrestrial ecosystems via emerging insects

Permanent ponds are valuable freshwater systems and biodiversity hotspots. They provide diverse ecosystem services (ES), including water quality improvement and supply, food provisioning and biodiversity support. This is despite being under significant pressure from multiple anthropogenic stressors and the impacts of ongoing global change. However, ponds are largely overlooked in management plans and legislation, and ecological research has focused on large freshwater ecosystems, such as rivers or lakes. Protection of ponds is often insufficient or indirectly provided via associated habitats such as wetlands. This phenomenon is likely exacerbated due to lacking a full-scale understanding of the importance of ponds. In this review, we provided a detailed overview of permanent ponds across Europe, including their usages and the biodiversity they support. By discussing the concepts of pondscape and metacommunity theory, we highlighted the importance of connectivity among and between ponds and identified fluxes of emerging insects as another ES of ponds. Those insects are rich in essential nutrients such as polyunsaturated fatty acids (PUFA), which are delivered through them to the terrestrial environment, however the extent and impact of this ES remains largely unexplored. Several potential stressors, especially related to ongoing global change, which influence pond diversity and integrity were discussed. To conclude this review, we provided our insights on future pond management. Adaptive measures, taking into account the pond system per se within the pondscape, were found to be the most promising to mitigate the loss of natural ponds and restore and conserve natural small water bodies as refuges and diversity hotspots in increasingly urbanized landscapes

The ecological role of permanent ponds in Europe ::a review of dietary linkages to terrestrial ecosystems via emerging insects

Permanent ponds are valuable freshwater systems and biodiversity hotspots. They provide diverse ecosystem services (ES), including water quality improvement and supply, food provisioning and biodiversity support. This is despite being under significant pressure from multiple anthropogenic stressors and the impacts of ongoing global change. However, ponds are largely overlooked in management plans and legislation, and ecological research has focused on large freshwater ecosystems, such as rivers or lakes. Protection of ponds is often insufficient or indirectly provided via associated habitats such as wetlands. This phenomenon is likely exacerbated due to lacking a full-scale understanding of the importance of ponds. In this review, we provided a detailed overview of permanent ponds across Europe, including their usages and the biodiversity they support. By discussing the concepts of pondscape and metacommunity theory, we highlighted the importance of connectivity among and between ponds and identified fluxes of emerging insects as another ES of ponds. Those insects are rich in essential nutrients such as polyunsaturated fatty acids (PUFA), which are delivered through them to the terrestrial environment, however the extent and impact of this ES remains largely unexplored. Several potential stressors, especially related to ongoing global change, which influence pond diversity and integrity were discussed. To conclude this review, we provided our insights on future pond management. Adaptive measures, taking into account the pond system per se within the pondscape, were found to be the most promising to mitigate the loss of natural ponds and restore and conserve natural small water bodies as refuges and diversity hotspots in increasingly urbanized landscapes