Dysregulation of epicardial adipose tissue in cachexia due to heart failure. the role of natriuretic peptides and cardiolipin

Background: Cachexia worsens long-term prognosis of patients with heart failure (HF). Effective treatment of cachexia is missing. We seek to characterize mechanisms of cachexia in adipose tissue, which could serve as novel targets for the treatment. Methods: The study was conducted in advanced HF patients (n = 52; 83% male patients) undergoing heart transplantation. Patients with ≥7.5% non-intentional body weight (BW) loss during the last 6 months were rated cachectic. Clinical characteristics and circulating markers were compared between cachectic (n = 17) and the remaining, BW-stable patients. In epicardial adipose tissue (EAT), expression of selected genes was evaluated, and a combined metabolomic/lipidomic analysis was performed to assess (i) the role of adipose tissue metabolism in the development of cachexia and (ii) potential impact of cachexia-associated changes on EAT-myocardium environment. Results: Cachectic vs. BW-stable patients had higher plasma levels of natriuretic peptide B (BNP; 2007 ± 1229 vs. 1411 ± 1272 pg/mL; P = 0.010) and lower EAT thickness (2.1 ± 0.8 vs. 2.9 ± 1.4 mm; P = 0.010), and they were treated with ~2.5-fold lower dose of both β-blockers and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACE/ARB-inhibitors). The overall pattern of EAT gene expression suggested simultaneous activation of lipolysis and lipogenesis in cachexia. Lower ratio between expression levels of natriuretic peptide receptors C and A was observed in cachectic vs. BW-stable patients (0.47 vs. 1.30), supporting activation of EAT lipolysis by natriuretic peptides. Fundamental differences in metabolome/lipidome between BW-stable and cachectic patients were found. Mitochondrial phospholipid cardiolipin (CL), specifically the least abundant CL 70:6 species (containing C16:1, C18:1, and C18:2 acyls), was the most discriminating analyte (partial least squares discriminant analysis; variable importance in projection score = 4). Its EAT levels were higher in cachectic as compared with BW-stable patients and correlated with the degree of BW loss during the last 6 months (r = −0.94; P = 0.036). Conclusions: Our results suggest that (i) BNP signalling contributes to changes in EAT metabolism in cardiac cachexia and (ii) maintenance of stable BW and ‘healthy’ EAT-myocardium microenvironment depends on the ability to tolerate higher doses of both ACE/ARB inhibitors and β-adrenergic blockers. In line with preclinical studies, we show for the first time in humans the association of cachexia with increased adipose tissue levels of CL. Specifically, CL 70:6 could precipitate wasting of adipose tissue, and thus, it could represent a therapeutic target to ameliorate cachexia

N-Octanoyl-Dopamine inhibits cytokine production in activated T-cells and diminishes MHC-class-II expression as well as adhesion molecules in IFN gamma-stimulated endothelial cells

IFN gamma enhances allograft immunogenicity and facilitates T-cell mediated rejection. This may cause interstitial fibrosis and tubular atrophy (IFTA), contributing to chronic allograft loss. We assessed if inhibition of T-cell activation by N-octanoyl dopamine (NOD) impairs adherence of activated T-cells to endothelial cells and the ability of activated T-cells to produce IFN gamma. We also assessed if NOD affects IFN gamma mediated gene expression in endothelial cells. The presence of NOD during T-cell activation significantly blunted their adhesion to unstimulated and cytokine stimulated HUVEC. Supernatants of these T-cells displayed significantly lower concentrations of TNF alpha and IFN gamma and were less capable to facilitate T-cell adhesion. In the presence of NOD VLA-4 (CD49d/CD29) and LFA-1 (CD11a/CD18) expression on T-cells was reduced. NOD treatment of IFN gamma stimulated HUVEC reduced the expression of MHC class II transactivator (CIITA), of MHC class II and its associated invariant chain CD74. Since IFTA is associated with T-cell mediated rejection and IFN gamma to a large extent regulates immunogenicity of allografts, our current data suggest a potential clinical use of NOD in the treatment of transplant recipients. Further in vivo studies are warranted to confirm these in vitro findings and to assess the benefit of NOD on IFTA in clinically relevant models

Plant trait and vegetation data along a 1314 m elevation gradient with fire history in Puna grasslands, Per\ufa

\ua9 2024. The Author(s). Alpine grassland vegetation supports globally important biodiversity and ecosystems that are increasingly threatened by climate warming and other environmental changes. Trait-based approaches can support understanding of vegetation responses to global change drivers and consequences for ecosystem functioning. In six sites along a 1314 m elevational gradient in Puna grasslands in the Peruvian Andes, we collected datasets on vascular plant composition, plant functional traits, biomass, ecosystem fluxes, and climate data over three years. The data were collected in the wet and dry season and from plots with different fire histories. We selected traits associated with plant resource use, growth, and life history strategies (leaf area, leaf dry/wet mass, leaf thickness, specific leaf area, leaf dry matter content, leaf C, N, P content, C and N isotopes). The trait dataset contains 3,665 plant records from 145 taxa, 54,036 trait measurements (increasing the trait data coverage of the regional flora by 420%) covering 14 traits and 121 plant taxa (ca. 40% of which have no previous publicly available trait data) across 33 families

Blood pressure control : helping patients take their medicine [Spanish]

Blood pressure control : helping patients take their medicine [Spanish]La presio\ucc?n arterial alta puede causar enfermedades cardiacas, accidentes cerebrovasculares, enfermedades renales y la muerte. Aproximadamente, el 70 % de los adultos en los EE. UU., de 65 an\ucc\u192oso ma\ucc?s, tiene la presio\ucc?n arterial alta y solo cerca de la mitad de ellos la tiene bajo control (por debajo de 140/90 mmHg). Los medicamentos para la presio\ucc?n arterial (junto con una alimentacio\ucc?n saludable y ejercicios) pueden proteger el corazo\ucc?n, el cerebro y los rin\ucc\u192ones, pero solo si los pacientes los toman y mantienen su presio\ucc?n arterial controlada. Sin embargo, al menos el 25 % de los adultos, de 65 an\ucc\u192os o ma\ucc?s, con la Parte D de Medicare que cubre los medicamentos recetados, no esta\ucc?n tomando sus medicamentos para la presio\ucc?n arterial segu\ucc?n las indicaciones. Esto significa que puede que se salten dosis o que dejen de tomarlos del todo. Los sistemas de atencio\ucc?n me\ucc?dica, incluidos proveedores, consultorios me\ucc?dicos, farmacias, hospitales, trabajadores de salud comunitaria y compan\ucc\u192i\ucc?as de seguros de salud, pueden trabajar con los pacientes para que sea ma\ucc?s fa\ucc?cil tomar los medicamentos.Los sistemas de atencio\ucc?n me\ucc?dica pueden:\ue2\u20ac\ua2 Simplificar el tratamiento para la presio\ucc?n arterial (p. ej., recetar suministros para 90 di\ucc?as y medicamentos en combinacio\ucc?n, y coordinar la entrega del suministro de pastillas para la misma fecha) y recetar medicamentos gene\ucc?ricos.\ue2\u20ac\ua2 \uef\ubf\ubc\uef\ubf\ubcInvolucrar a todo el equipo de atencio\ucc?n me\ucc?dica en varios puntos de atencio\ucc?n para garantizar que los pacientes este\ucc?n tomando sus medicamentos segu\ucc?n las indicaciones y para abordar las preocupaciones de los pacientes acerca de los efectos secundarios. Implementar protocolos de tratamientos eficaces para la presio\ucc?n arterial en la pra\ucc?ctica cli\ucc?nica. http://go.usa.gov/xjf59\ue2\u20ac\ua2 Fomentar el uso de monitores de la presio\ucc?n arterial en casa y arti\ucc?culos fa\ucc?ciles de usar (p. ej., registros de la presio\ucc?n arterial y aplicaciones mo\ucc?viles) para hacerle seguimiento a los niveles de la presio\ucc?n arterial y compartir la informacio\ucc?n.\ue2\u20ac\ua2 Abordar los obsta\ucc?culos financieros, tales como altos copagos y deducibles.CS267220A MLS269737A2016-09-vitalsigns.pd