Endothelial Progenitor Cells and Cardiovascular Events in Patients with Chronic Kidney Disease – a Prospective Follow-Up Study

BACKGROUND: Endothelial progenitor cells (EPCs) mediate vascular repair and regeneration. Their number in peripheral blood is related to cardiovascular events in individuals with normal renal function. METHODS: We evaluated the association between functionally active EPCs (cell culture) and traditional cardiovascular risk factors in 265 patients with chronic kidney disease stage V receiving hemodialysis therapy. Thereafter, we prospectively assessed cardiovascular events, e.g. myocardial infarction, percutaneous transluminal coronary angioplasty (including stenting), aorto-coronary bypass, stroke and angiographically verified stenosis of peripheral arteries, and cardiovascular death in this cohort. RESULTS: In our patients EPCs were related only to age (r=0.154; p=0.01). During a median follow-up period of 36 months 109 (41%) patients experienced a cardiovascular event. In a multiple Cox regression analysis, we identified EPCs (p=0.03) and patient age (p=0.01) as the only independent variables associated with incident cardiovascular events. Moreover, a total of 70 patients died during follow-up, 45 of those due to cardiovascular causes. Log rank test confirmed statistical significance for EPCs concerning incident cardiovascular events (p=0.02). CONCLUSIONS: We found a significant association between the number of functionally active EPCs and cardiovascular events in patients with chronic kidney disease. Thus, defective vascular repair and regeneration may be responsible, at least in part, for the enormous cardiovascular morbidity in this population

The effects of physical exercise on plasma levels of relaxin, NTproANP, and NTproBNP in patients with ischemic heart disease

The insulin-like and vasodilatatory polypeptide relaxin (RLX), formerly known as a pregnancy hormone, has gained interest as a potential humoral mediator in human heart failure. Controversy exists about the relation between plasma levels of RLX and the severity of heart failure. The present study was designed to determine the course of RLX, atrial, and brain natriuretic peptide (NT-proANP and NT-proBNP) during physical exercise in patients with ischemic heart disease (IHD) and to relate hormone levels to peak cardiac power output (CPO) as a measure of cardiopulmonary function with prognostic relevance. 40 patients with IHD were studied during right-heart-catheterization at rest and during supine bicycle ergometry. RLX, NTproBNP, and NTproANP were determined before, during exercise, and after recovery. NT-proANP and NT-proBNP levels increased during maximal charge, and recovery while RLX levels decreased. Cardiac power output at maximal charge correlated inversely with NTproANP and NTproBNP but positively with RLX. Patients with high degree heart failure (CPO < 1.96 W) had higher NTproANP and NTproB-NP and lower RLX levels than patients with low degree heart failure. While confirming the role of NTproANP and NTproBNP as markers for the severity of heart failure, the present data do not support the concept that plasma levels of RLX are related to the severity of myocardial dysfunction and that systemic RLX acts as a compensatory vasodilatatory response hormone in ischemic heart disease

Un enfoque fisiológico para los procesos oceánicos y los cambios glaciares-interglaciares del CO2 atmosférico

18 pages, 6 figures, 1 table[EN] One possible path for exploring the Earth’s far-from-equilibrium homeostasis is to assume that it results from the organisation of optimal pulsating systems, analogous to that in complex living beings. Under this premise it becomes natural to examine the Earth’s organisation using physiological-like variables. Here we identify some of these main variables for the ocean’s circulatory system: pump rate, stroke volume, carbon and nutrient arterial-venous differences, inorganic nutrients and carbon supply, and metabolic rate. The stroke volume is proportional to the water transported into the thermocline and deep oceans, and the arterial-venous differences occur between recently-upwelled deep waters and very productive high-latitudes waters, with atmospheric CO2 being an indicator of the arterial-venous inorganic carbon difference. The metabolic rate is the internal-energy flux (here expressed as flux of inorganic carbon in the upper ocean) required by the system’s machinery, i.e. community respiration. We propose that the pump rate is set externally by the annual cycle, at one beat per year per hemisphere, and that the autotrophic ocean adjusts its stroke volume and arterial-venous differences to modify the internal-energy demand, triggered by long-period astronomical insolation cycles (external-energy supply). With this perspective we may conceive that the Earth’s interglacial-glacial cycle responds to an internal organisation analogous to that occurring in living beings during an exercise-recovery cycle. We use an idealised double-state metabolic model of the upper ocean (with the inorganic carbon/nutrients supply specified through the overturning rate and the steady-state inorganic carbon/nutrients concentrations) to obtain the temporal evolution of its inorganic carbon concentration, which mimics the glacial-interglacial atmospheric CO2 pattern[ES] Un posible camino para el estudio de la homeóstasis fuera-de-equilibrio de la tierra es suponer que resulta de la organización de sistemas pulsátiles optimizados, análoga a aquélla en seres vivos complejos. Bajo esta premisa parece natural examinar la organización de la tierra utilizando variables de tipo fisiológico. Aquí identificamos algunas de las principales variables del sistema circulatorio oceánico: tasa de bombeo del corazón, volumen de latido, diferencias arteriovenosas de carbono y nutrientes, suministro de carbono y nutrientes inorgánicos, y tasa metabólica. El volumen de latido es proporcional al transporte de agua hacia la termoclina y océano profundo, y las diferencias arterio-venosas ocurren entre las aguas profundas recientemente afloradas y aquellas altamente productivas de altas latitudes, con el CO2 atmosférico siendo un indicador de la diferencia arterio-venosa de carbono inorgánico. La tasa metabólica es el flujo de energía interna (aquí expresado como flujo de carbono inorgánico en el océano superior) requerido por la maquinaria que sostiene el sistema, i.e. respiración total de la comunidad. Se propone que la tasa de latido está impuesta externamente, un latido por año por hemisferio, y que el océano autotrófico ajusta su volumen de latido y las diferencias arteriovenosas a cambios en la demanda de energía interna, inducido por ciclos de insolación astronómica de largo período (suministro de energía externa). Bajo esta perspectiva podemos concebir que el ciclo interglacial-glacial de la tierra responde a una organización interna análoga a la que ocurre en seres vivos durante un ciclo de ejercicio-recuperación. Se utiliza un modelo metabólico idealizado de dos estados para el océano superior (con el suministro de carbono/nutrientes inorgánicos especificado mediante la tasa de recirculación de aguas profundas y las concentraciones de carbono/nutrientes inorgánicos en estado estacionario) para obtener la evolución temporal de su concentración de carbono inorgánico, la cual mimetiza el patrón glacial-interglacial del CO2 atmosféricoThis work was supported by the Spanish government through the CANOA project (CTM2005-00444/MAR)Peer reviewe

Root uptake and metabolization of Alternaria toxins by winter wheat plants using a hydroponic system

Fungi of the genus Alternaria are ubiquitous in the environment. Their mycotoxins can leach out of contaminated plants or crop debris into the soil entering the plant via the roots. We aim to evaluate the importance of this entry pathway and its contribution to the overall content of Alternaria toxins (ATs) in wheat plants to better understand the soil–plant-phytopathogen system. A hydroponic cultivation system was established and wheat plants were cultivated for up to two weeks under optimal climate conditions. One half of the plants was treated with a nutrient solution spiked with alternariol (AOH), alternariol monomethyl ether (AME), and tenuazonic acid (TeA), whereas the other half of the plants was cultivated without mycotoxins. Plants were harvested after 1 and 2 weeks and analyzed using a QuEChERS-based extraction and an in-house validated LC–MS/MS method for quantification of the ATs in roots, crowns, and leaves separately. ATs were taken up by the roots and transported throughout the plant up to the leaves after 1 as well as 2 weeks of cultivation with the roots showing the highest ATs levels followed by the crowns and the leaves. In addition, numerous AOH and AME conjugates like glucosides, malonyl glucosides, sulfates, and di/trihexosides were detected in different plant compartments and identified by high-resolution mass spectrometry. This is the first study demonstrating the uptake of ATs in vivo using a hydroponic system and whole wheat plants examining both the distribution of ATs within the plant compartments and the modification of ATs by the wheat plants

Evaluation of the zucker diabetic fatty (ZDF) rat as a model for human disease based on urinary peptidomic profiles

Representative animal models for diabetes-associated vascular complications are extremely relevant in assessing potential therapeutic drugs. While several rodent models for type 2 diabetes (T2D) are available, their relevance in recapitulating renal and cardiovascular features of diabetes in man is not entirely clear. Here we evaluate at the molecular level the similarity between Zucker diabetic fatty (ZDF) rats, as a model of T2D-associated vascular complications, and human disease by urinary proteome analysis. Urine analysis of ZDF rats at early and late stages of disease compared to age- matched LEAN rats identified 180 peptides as potentially associated with diabetes complications. Overlaps with human chronic kidney disease (CKD) and cardiovascular disease (CVD) biomarkers were observed, corresponding to proteins marking kidney damage (eg albumin, alpha-1 antitrypsin) or related to disease development (collagen). Concordance in regulation of these peptides in rats versus humans was more pronounced in the CVD compared to the CKD panels. In addition, disease-associated predicted protease activities in ZDF rats showed higher similarities to the predicted activities in human CVD. Based on urinary peptidomic analysis, the ZDF rat model displays similarity to human CVD but might not be the most appropriate model to display human CKD on a molecular level

Low oxygen tension primes aortic endothelial cells to the reparative effect of tissue-protective cytokines

Erythropoietin (EPO) has both erythropoietic and tissue-protective properties. The EPO analogues carbamylated EPO (CEPO) and pyroglutamate helix B surface peptide (pHBSP) lack the erythropoietic activity of EPO but retain the tissue-protective properties that are mediated by a heterocomplex of EPO receptor (EPOR) and the β common receptor (βCR). We studied the action of EPO and its analogues in a model of wound healing where a bovine aortic endothelial cells (BAECs) monolayer was scratched and the scratch closure was assessed over 24 h under different oxygen concentrations. We related the effects of EPO and its analogues on repair to their effect on BAECs proliferation and migration (evaluated using a micro-Boyden chamber). EPO, CEPO and pHBSP enhanced scratch closure only at lower oxygen (5%), while their effect at atmospheric oxygen (21%) was not significant. The mRNA expression of EPOR was doubled in 5% compared to 21% oxygen, and this was associated with increased EPOR assessed by immunofluorescence and Western blot. By contrast βCR mRNA levels were similar in 5% and 21% oxygen. EPO and its analogues increased both BAECs proliferation and migration, suggesting that both may be involved in the reparative process. The priming effect of low oxygen tension on the action of tissue-protective cytokines may be of relevance to vascular disease, including atherogenesis and restenosis