Abstract We have analysed whether pulmonary arterial hypertension (PAH) alters the rat faecal microbiota. Wistar rats were injected with VEGF receptor antagonist SU5416 (20 mg/kg s.c.) and followed for 2 weeks kept in hypoxia (10% O , PAH) or vehicle normoxia (controls). Faecal samples obtained microbiome composition was determined by 16S rRNA gene sequencing bioinformatic analysis. No effect of PAH on global found (α- β-diversity). However, PAH-exposed showed gut dysbiosis as indicated a...

Key points The expression of miR‐1 is increased in lungs from the Hyp/Su5416 PAH rat model. Pulmonary artery smooth muscle cells this animal model are more depolarized and show decreased activity voltage‐dependent potassium channel (Kv)1.5. directly targets Kv1.5 channels, reduces induces membrane depolarization. Antagomir‐1 prevents downregulation depolarization induced by hypoxia/Su5416 exposition. Abstract Impairment (Kv) plays a central role development cardiovascular diseases, including...

The NO/cGMP pathway represents a major physiological signalling controlling tone in pulmonary arteries (PA), and drugs activating this are used to treat arterial hypertension. Kv channels expressed PA smooth muscle cells (PASMCs) key determinants of vascular tone. We aimed analyse the contribution 1.5 7 electrophysiological vasodilating effects evoked by NO donors GC stimulator riociguat PA.Kv currents were recorded isolated rat PASMCs using patch-clamp technique. Vascular reactivity was...

Vitamin D (VitD) receptor regulates the expression of several genes involved in signaling pathways affected pulmonary hypertension (PH). VitD deficiency is highly prevalent PH, and low levels are associated with poor prognosis. We investigated if may predispose to or exacerbate PH. Male Wistar rats were fed a standard VitD-free diet for 5 wk. Next, further divided into controls which was induced by single dose Su-5416 (20 mg/kg) exposure hypoxia (10% O2) 2 had no effect on pressure normoxic...

Introduction: Epidemiological studies suggest a relationship between vitamin D deficiency and cardiovascular respiratory diseases. However, whether total, bioavailable, and/or free levels have prognostic role in pulmonary arterial hypertension (PAH) is unknown. We aimed to determine 25-hydroxy-vitamin (25(OH)vitD) plasma their value PAH patients. Methods: In 67 samples of from Spanish patients with idiopathic, heritable, or drug-induced were obtained the PH Biobank compared cohort 100...

Human immunodeficiency virus (HIV) infection is an established risk factor for pulmonary arterial hypertension (PAH); however, the pathogenesis of HIV-related PAH remains unclear. Since K + channel dysfunction a common marker in most forms PAH, our aim was to analyze whether expression HIV proteins associated with impairment function vascular bed. transgenic mice (Tg26) expressing seven nine viral and wild-type (WT) were used. Hemodynamic assessment performed by echocardiography...

K+ channels play a fundamental role regulating membrane potential of pulmonary artery (PA) smooth muscle cells and their impairment is common feature in arterial hypertension (PAH). voltage-gated channel subfamily Q (KCNQ1-5) or Kv7 regulatory subunits E (KCNE) are known to regulate vascular tone, but whether function impaired PAH how this can affect the rationale for targeting remains unknown. Here, we have studied Kv7/KCNE rat PA possible alteration PAH. Using patch-clamp technique, found...

Background: Vitamin D (vitD) deficiency is highly prevalent in patients with pulmonary arterial hypertension (PAH). Moreover, PAH-patients lower levels of vitD have worse prognosis. We hypothesize that recovering optimal an animal model PAH previously depleted improves the hemodynamics, endothelial dysfunction and ionic remodeling. Methods: Male Wistar rats were fed a vitD-free diet for five weeks then received single dose Su5416 (20 mg/Kg) exposed to chronic hypoxia (10% O2) three induce...

Diabetes is a very strong predictor of chronic systemic vascular diseases and acute cardiovascular events. Recently, associations between metabolic disorders pulmonary hypertension have also been reported in both humans animal models. In order to get some further insight into the relationship with obesity, insulin resistance hyperglycemia, herein we used Zucker diabetic fatty rats (ZDF/clr-lepr fa) at 20 weeks fed standard diet compared their lean littermates (ZL). ZDF were obese, had...

Background: Despite increasing evidence suggesting that pulmonary arterial hypertension (PAH) is a complex disease involving vasoconstriction, thrombosis, inflammation, metabolic dysregulation and vascular proliferation, all the drugs approved for PAH mainly act as vasodilating agents. Since excessive TGF-β signaling believed to be critical factor in remodeling, we hypothesized blocking TGFβ-activated kinase 1 (TAK-1), alone or combination with vasodilator therapy (i.e., riociguat) could...

Introduction Current treatment with vasodilators for pulmonary hypertension associated respiratory diseases is limited by their inhibitory effect on hypoxic vasoconstriction (HPV) and uncoupling effects ventilation-perfusion (V'/Q'). Hypoxia also a well-known modulator of the nitric oxide (NO) pathway, may therefore differentially affect responses to phosphodiesterase 5 (PDE5) inhibitors soluble guanylyl cyclase (sGC) stimulators. So far, sGC stimulator riociguat HPV have been poorly...

Current approved therapies for pulmonary hypertension (PH) aim to restore the balance between endothelial mediators in circulation. These drugs may exert vasodilator effects on poorly oxygenated vessels. This lead derivation of blood perfusion towards low ventilated alveoli, i.e., producing ventilation-perfusion mismatch, with detrimental gas exchange. The this study is analyze oxygen-sensitivity vitro 25 currently used or potentially useful PH. Additionally, analyses effectiveness these...

Vitamin D deficiency is recognized as a worldwide pandemic. Pulmonary arterial hypertension (PAH) severe and progressive vascular disease with poor prognosis. Interestingly, calcitriol, the active form of vitamin D, modulates several signaling pathways affected in PAH. The aims this study were to examine prevalence PAH-patients investigate if may predispose A retrospective cohort 67 Spanish-PAH patients, whose plasma samples obtained from CIBERES Biobank clinical parameters Spanish Arterial...

<b>Background:</b> Pulmonary arterial hypertension (PAH) is a progressive disease affecting the lung vasculature, characterized by sustained vasoconstriction, vascular remodeling and thrombosis. In recent years, altered immune inflammatory processes are being considered as pathological hallmarks of disease. fact, several studies have reported relationship between gut dysbiosis cardiovascular diseases. We hypothesized that development PAH may be associated to changes in intestinal bacterial...

Current evidences suggest that the therapeutic effects of mesenchymal stem cells (MSCs) are linked to their immunomodulatory and anti-inflammatory properties, mainly mediated by secretion extracellular vesicles (EVs). The aim this study was analyse whether MSCs-derived EVs able prevent pulmonary vascular dysfunction induced lipopolysaccharide (LPS). released umbilical cord blood-derived MSCs were obtained differential ultracentrifugation. Rat arteries (PA) treated overnight with LPS in...

Endothelial and voltage-dependent potassium channel (Kv) dysfunction plays a central role in the development of pulmonary arterial hypertension (PAH). MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression by binding to 39UTR region specific mRNAs. miR-1 levels elevated PAH-patients, but their pathophysiologic is unclear. The aim this study was analyze effects on endothelial Kv function arteries (PA). activity were studied PA from healthy animals transfected with or...

Uric acid (UA) is a damage-associated molecular pattern (DAMP) released from injured or infected cells. Beyond maximal solubility, UA precipitates and forms monosodium urate (MSU) crystals which can activate the innate immune system. levels are increased in several respiratory diseases including ARDS, pulmonary hypertension COPD. The aim of this study was to analyse whether MSU able induce inflammation on their own might exacerbate lung injury induced by lipopolysaccharide (LPS). Rats...

Background: Despite increasing evidences suggest that pulmonary arterial hypertension (PAH) is a complex disease involving vasoconstriction, thrombosis, inflammation, metabolic dysregulation and vascular proliferation, all the drugs approved for PAH mainly act as vasodilating agents. Since excessive TGF-B signalling believed to be critical factor in remodelling, we hypothesized blocking TGFB-activated kinase 1 (TAK-1), alone or combination with vasodilator therapy (i.e., riociguat) could...

Background. Multiple studies have reported a worldwide deficiency of vitamin D. Epidemiological also suggest relationship between D and cardiovascular diseases. Pulmonary arterial hypertension (PAH) is severe progressive vascular disease characterized by vasoconstriction, remodelling thrombosis. Interestingly, calcitriol, the active form D, modulates several signalling pathways affected in PAH. The aims this study were to investigate if may predispose or exacerbate PAH analyze levels its...