Activation profile of pro-inflammatory cytokines in acute cardiac overload

INTRODUCTION:Pro-inflammatory cytokines have been implicated in ventricular remodeling during heart failure progression. In the present study, we investigated the effects of acute volume and RV pressure overload on biventricular hemodynamics and myocardial gene expression of IL-6 and TNF-alpha.METHODS:Male Wistar rats (n = 45) instrumented with RV and LV tip micromanometers were randomly assigned to one of three protocols: i) acute RV pressure overload (PrOv) induced by pulmonary trunk banding in order to double RV peak systolic pressure, for 120 or 360 min; ii) acute volume overload (VolOv) induced by dextran40 infusion (5 ml/h), for 120 or 360 min; iii) Sham. Free wall samples from the RV and LV were collected for mRNA quantification.RESULTS:In the RV, acute overload induced IL-6 and TNF-alpha gene expression, higher in VolOv (IL-6: + 669.7 +/- 263.4%; TNF-alpha: + 5149.9 +/- 1099.0%; 360 min) than in PrOv (IL-6: + 64.9 +/- 44.2%; TNF-alpha: + 628.1 +/- 229.3%; 360 min). In PrOv, TNF-alpha mRNA levels in the LV were increased, in the absence of ventricular overload. IL-6 and TNF-alpha mRNA levels did not correlate in the LV, while in the RV a positive correlation was found (r = 0.574; p < 0.001).CONCLUSIONS:Acute cardiac overload induces overexpression of pro-inflammatory cytokines. This gene activation is not uniform, being higher in volume overload and involving both load-dependent and load-independent mechanisms

Endogenous production of ghrelin and beneficial effects of its exogenous administration in monocrotaline-induced pulmonary hypertension

We investigated the endogenous production of ghrelin as well as cardiac and pulmonary vascular effects of its administration in a rat model of monocrotaline (MCT)-induced pulmonary hypertension (PH). Adult Wistar rats randomly received a subcutaneous injection of MCT (60 mg/kg) or an equal volume of vehicle. One week later, animals were randomly assigned to receive a subcutaneous injection of ghrelin (100 mug/kg bid for 2 wk) or saline. Four groups were analyzed: normal rats treated with ghrelin (n = 7), normal rats injected with saline (n = 7), MCT rats treated with ghrelin (n = 9), and MCT rats injected with saline (n = 9). At 22-25 days, right ( RV) and left ventricular (LV) pressures were measured, heart and lungs were weighted, and samples were collected for histological and molecular analysis. Endogenous production of ghrelin was almost abolished in normal rats treated with ghrelin. In MCT-treated animals, pulmonary expression of ghrelin was preserved, and RV myocardial expression was increased more than 20 times. In these animals, exogenous administration of ghrelin attenuated PH, RV hypertrophy, wall thickening of peripheral pulmonary arteries, and RV diastolic disturbances and ameliorated LV dysfunction, without affecting its endogenous production. In conclusion, decreased tissular expression of ghrelin in healthy animals but not in PH animals suggests a negative feedback in the former that is lost in the latter. A selective increase of ghrelin mRNA levels in the RV of animals with PH might indicate distinct regulation of its cardiac expression. Finally, ghrelin administration attenuated MCT-induced PH, pulmonary vascular remodeling, and RV hypertrophy, indicating that it may modulate PH

Acute changes of biventricular gene expression in volume and right ventricular pressure overload

Objective: We investigated the effects of acute volume and RV pressure overload on biventricular function and gene expression of BNP, proinflammatory cytokines (IL-6 and TNF-alpha), iNOS, growth factors (IGF-1, ppET-1), ACE and Ca2+-handling proteins (SERCA2a, phospholamban and calsequestrin). Methods: Male Wistar rats (n =45) instrumented with pressure tip micromanorneters in right (RV) and left ventricular (LV) cavities were assigned to one of three protocols: i) Acute RV pressure overload induced by pulmonary trunk banding in order to double RV peak systolic pressure, during 120 or 360 min; ii) acute volume overload induced by dextran40 infusion (5 ml/h), during 120 or 360 min; iii) Sham. RV and LV samples were collected for mRNA quantification. Results: BNP upregulation was restricted to the overloaded ventricles. TNF-alpha, IL-6, ppET-1, SERCA2a and phospholamban gene activation was higher in volume than in pressure overload. IGF-1 overexpression was similar in both types of overload, but was limited to the RV. TNF-alpha and CSQ mRNA levels were increased in the non-overloaded LV after pulmonary trunk banding. No significant changes were detected in ACE or iNOS expression. RV end-diastolic pressures positively correlated with local expression of BNP, TNF-alpha, IL-6, IGF- 1, ppET-1 and SERCA2a, while RV peak systolic pressures correlated only with local expression of IL-6, IGF-1 and ppET-1. Conclusions: Acute cardiac overload alters myocardial gene expression profile, distinctly in volume and pressure overload. These changes correlate more closely with diastolic than with systolic load. Nonetheless, gene activation is also present in the non-overloaded LV of selectively RV overloaded hearts

Ghrelin reverses molecular, structural and hemodynamic alterations of the right ventricle in pulmonary hypertension

Ghrelin is an endogenous peptide that has a dual effect by activating specific receptors and by stimulating release of growth hormone. There is increasing evidence that ghrelin has a potent vasodilator effect. Recently, we demonstrated that exogenous administration of ghrelin modulates its endogenous levels and attenuates the majority of alterations induced by monocrotaline (MCT). In the present study, we evaluate the effects of chronic administration of ghrelin on hemodynamic and morphometric parameters of the right ventricle, as well as on myocardial levels of SERCA2a and endothelin-1. Adult Wistar rats were injected with MCT (60 mg/kg, sc) or just the vehicle (day 0). One week later, the animals treated with MCT were randomly divided into two groups and treated with ghrelin (100 microg/kg, bid, sc) or with a similar volume of vehicle. Between days 21-25 the animals were instrumented to record right ventricular (RV) pressures and samples were collected for morphological and molecular analysis. Ghrelin treatment attenuated the effects of MCT, namely: RV myocyte fiber diameter, pulmonary vascular remodeling (evaluated by % medial wall thickness of peripheral arteries), RV peak systolic pressure, RV end-diastolic pressure, time constant tau, and SERCA2a and endothelin-1 mRNA levels. Chronic ghrelin administration attenuates MCT-induced pulmonary hypertension, vascular remodeling and RV hypertrophy. These results suggest a potential therapeutic role for the ghrelin-growth hormone axis in pulmonary hypertension

Structure and regional representativeness of the herpetofauna from Parque Estadual da Serra de Caldas Novas, Cerrado, Central Brazil

Amphibians and reptiles are diversified in the Cerrado biome but have been threatened by habitat loss and fragmentation, as well as lack of understanding of their distribution. Therefore, collection and organization of information about species in natural environments are essential for conservation, especially in Protected areas (PAs) and their adjacent zones. We present information about the composition and structure of the herpetofauna from Parque Estadual da Serra de Caldas Novas (PESCAN) and its representativeness in comparison to other PAs in the Cerrado. Fieldwork was conducted in 12 sampling sites from February 2009 to February 2010, using active search and pitfall traps. We recorded 41 species of amphibians, with greatest richness in sites with open vegetation and water bodies. Reptiles were represented by 32 species, with the greatest species richness in cerrado open environments. Both amphibian and reptile communities were more similar to those from geographically closer PAs and located in the central region of the Cerrado (State of Goiás and Distrito Federal). The PESCAN holds 24.85% and 17.98% of amphibians and reptiles species occurring in Cerrado PAs, respectivelly. This large representativeness and the high number of endemisms (18 amphibians and 7 reptiles) emphasize the importance of the PESCAN, together with other PAs, for the maintenance of regional biodiversity. In addition, we also encourage researches evaluating amphibian and reptile communities outside PAs, such as legal reserves, and we suggest new approaches to study the biodiversity of protected areas. © 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group

Phylogenetic investigation of enteric bovine coronavirus in Ireland reveals partitioning between European and global strains

Background: Bovine coronavirus is a primary cause of neonatal calf diarrhea worldwide, and is also associated with acute diarrhea in adult cattle during the winter season. There are no reports on molecular characterization of bovine coronavirus in Ireland, and little data exists apart from serological studies. Findings: In this study, 11 neonatal (mean age 9 days) calf BCoV strains from the south of Ireland were collected over a one year period and characterized using molecular methods. The spike gene which encodes a protein involved in viral entry, infectivity and immune response shows the most variability amongst the isolates and was subsequently selected for in depth analysis. Phylogenetic analysis of the spike gene revealed that the Irish strains clustered with novel BCoV strains from Europe in a unique clade, possibly indicating lineage partitioning. Direct analysis of alignments identified amino acid changes in the spike protein unique to the Irish clade. Conclusion: Thus, monitoring of bovine coronavirus in Ireland is important as the current isolates in circulation in the south of Ireland may be diverging from the available vaccine strain, which may have implications regarding future BCoV vaccine efficacy