Role for miR-204 in human pulmonary arterial hypertension

Reduced miR-204 expression facilitates the excessive proliferation and apoptosis resistance of pulmonary artery smooth muscle cells characteristic of human pulmonary arterial hypertension

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Hypoxie chronique, circulation pulmonaire et coeur droit (approche expérimentale, clinique et thérapeutique (DHEA))

Nous avons exploré le modèle d'hypoxie hypobarique chez le rat, en intégrant l'exploration hémodynamique, l'évaluation des tissus et de la cellule musculaire. La déhydroépiandrostérone (DHEA), prévient et traite l'HTAP secondaire à l'hypoxie chronique en augmentant l'expression des canaux potassiques calcium et voltages dépendants probablement par la modulation de l'état redox. L'hypoxie chronique entraîne une hypertrophie des myocytes qui permet une augmentation des performances contractiles afin de répondre à l'élévation de la post charge du ventricule droit (VD). Cette hypertrophie est associée à une diminution de la densité cellulaire myocytaire. Nous avons montré que la DHEA diminue l'hypertrophie myocytaire et l'augmentation des pressions développées par le VD. Dans un deuxième temps nous avons montré que la récupération normoxique post hypoxique induit une dysfonction ventriculaire droite associée à une diminution de la densité myocytaire et des altérations mitochondriales (mitochondries plus nombreuses, plus petites et ayant une ultrastructure anormale). La DHEA prévient la diminution de la densité myocytaire et les altérations mitochondriales secondaires à cette phase de récupération normoxique.Pulmonary artery (PA) hypertension and right ventricule (RV) was studied in a chronic hypoxic hypertension model in the rat. Increase in PA pressure, RV hypertrophy and PA remodelling were almost entirely prevented after oral dehidroepiandrosterone (DHEA) administration. In PA smooth muscle cell DHEA reduced the level of intracellular calcium. The effect of DHEA appears to involved a large conductance Ca puissance 2+ activated potassium channel (BKCa)-dependant stimulatory mechanism, at both function and expression levels via a redox dependant pathway. During CH, elevated PA pressures and RV-developed pressures were decreased by DHEA, RV remodelling and myocyte hypertrophy were partially prevented by DHEA. CH induced a decrease in myocyte density which was not attenuated by DHEA. Electron microscopy showed an increase in mitochondrial surface area in the CH and CH-DHEA groups compared to the DHEA group. We have shown that 21 days of normoxia (recovery period) after 21 days of hypoxia is accompanied by normalization of the pulmonary pressures and RV hypertrophy but with contractile dysfunction and histologic alterations. During normoxic recovery, the decrease in myocyte density and in mitochondrial surface area was prevented by DHEA.BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Effect of chronic hypoxia on pulmonary artery blood velocity in rats as assessed by electrocardiography-triggered three-dimensional time-resolved MR angiography

International audienc

Altered vasoreactivity in neonatal rats with pulmonary hypertension associated with bronchopulmonary dysplasia: Implication of both eNOS phosphorylation and calcium signaling

International audienc