Eplerenone attenuates pathological pulmonary vascular rather than right ventricular remodeling in pulmonary arterial hypertension

BACKGROUND: Aldosterone is a mineralocorticoid hormone critically involved in arterial blood pressure regulation. Although pharmacological aldosterone antagonism reduces mortality and morbidity among patients with severe left-sided heart failure, the contribution of aldosterone to the pathobiology of pulmonary arterial hypertension (PAH) and right ventricular (RV) heart failure is not fully understood. METHODS: The effects of Eplerenone (0.1% Inspra® mixed in chow) on pulmonary vascular and RV remodeling were evaluated in mice with pulmonary hypertension (PH) caused by Sugen5416 injection with concomitant chronic hypoxia (SuHx) and in a second animal model with established RV dysfunction independent from lung remodeling through surgical pulmonary artery banding. RESULTS: Preventive Eplerenone administration attenuated the development of PH and pathological remodeling of pulmonary arterioles. Therapeutic aldosterone antagonism - starting when RV dysfunction was established - normalized mineralocorticoid receptor gene expression in the right ventricle without direct effects on either RV structure (Cardiomyocyte hypertrophy, Fibrosis) or function (assessed by non-invasive echocardiography along with intra-cardiac pressure volume measurements), but significantly lowered systemic blood pressure. CONCLUSIONS: Our data indicate that aldosterone antagonism with Eplerenone attenuates pulmonary vascular rather than RV remodeling in PAH

Cystathionine γ Lyase Sulfhydrates the RNA Binding Protein Human Antigen R to Preserve Endothelial Cell Function and Delay Atherogenesis

Hydrogen sulfide (H2S), generated by cystathionine γ lyase (CSE), is an important endogenous regulator of vascular function. The aim of the present study was to investigate the control and consequences of CSE activity in endothelial cells under physiological and proatherogenic conditions

Author Correction: Deficiency of Axl aggravates pulmonary arterial hypertension via BMPR2.

Abstract: Pulmonary arterial hypertension (PAH), is a fatal disease characterized by a pseudo-malignant phenotype. We investigated the expression and the role of the receptor tyrosine kinase Axl in experimental (i.e., monocrotaline and Su5416/hypoxia treated rats) and clinical PAH. In vitro Axl inhibition by R428 and Axl knock-down inhibited growth factor-driven proliferation and migration of non-PAH and PAH PASMCs. Conversely, Axl overexpression conferred a growth advantage. Axl declined in PAECs of PAH patients. Axl blockage inhibited BMP9 signaling and increased PAEC apoptosis, while BMP9 induced Axl phosphorylation. Gas6 induced SMAD1/5/8 phosphorylation and ID1/ID2 increase were blunted by BMP signaling obstruction. Axl association with BMPR2 was facilitated by Gas6/BMP9 stimulation and diminished by R428. In vivo R428 aggravated right ventricular hypertrophy and dysfunction, abrogated BMPR2 signaling, elevated pulmonary endothelial cell apoptosis and loss. Together, Axl is a key regulator of endothelial BMPR2 signaling and potential determinant of PAH

PASANDO REVISTA A LAS TROPAS EN LA LLEGADA DEL REY [Material gráfico]

Copia digital. Madrid : Ministerio de Educación, Cultura y Deporte. Subdirección General de Coordinación Bibliotecaria, 201

Maintained right ventricular pressure overload induces ventricular-arterial decoupling in mice.

Assessment of right ventricular (RV) function in rodents is a challenge due to the complex RV anatomy and structure. Subsequently, the best characterization of RV function is achieved by accurate cardiovascular phenotyping, involving a combination of non-invasive imaging and intra-cardiac pressure-volume measurements. We sought to investigate the feasibility of two complementary phenotyping techniques for the evaluation of RV function in an experimental mouse model of sustained RV pressure overload. Mice underwent either Sham surgery (n = 5) or pulmonary artery banding (PAB) (n = 8) to induce isolated RV pressure overload. After three weeks indices of RV function were assessed by echocardiography (Vevo2100) and closed chest-derived invasive pressure-volume measurements (PVR-1030). PAB resulted in RV hypertrophy and dilatation accompanied by systolic and diastolic dysfunction. Invasive RV hemodynamic measurements demonstrate an increased end-systolic as well as arterial elastance after PAB as compared to sham, resulting in ventricular-arterial decoupling. Regression analysis revealed that TAPSE is rather correlated with ventricular-arterial coupling (r² = 0.77, P = 0.002) than RV contractility (r² = -0.61, P = 0.07). Furthermore, IVRT/RR and E/E' correlate well with RV end-diastolic pressure (r² = 0.87, P = 0.0001 and r² = 0.82, P = 0.0009; respectively). Commonly used indices of systolic RV function are associated with RV-arterial coupling rather than contractility, while diastolic indices are interrelated with end-diastolic pressure where there is maintained pressure overload. This article is protected by copyright. All rights reserved

Microscopic computed tomography with AI-CNN- powered image analysis: the path to phenotype the bleomycin-induced lung injury. Supplemental Figure

Supplemental figures 1 and 2</p