IDO-1 Promotes Pulmonary Vascular Remodeling Via Kynurenine Pathway in Pulmonary Arterial Hypertension.

Background: Activation of the plasma kynurenine pathway (KP) may contribute to the progression of pulmonary arterial hypertension (PAH). We investigated the functional role and molecular mechanisms of KP activation in PAH.

Methods: KP activity was measured in the lungs and plasma of humans and rodents with pulmonary hypertension (PH).

Bone morphogenetic protein-9 controls pulmonary vascular growth and remodeling.

Pulmonary arterial hypertension (PAH) and hereditary hemorrhagic telangiectasia (HHT) are two distinct vascular diseases linked to impaired signaling through bone morphogenetic protein (BMP) receptor complexes in endothelial cells. Although BMP-9 plays a central role in activating this pathway by binding to ALK1 and BMPR-II, its precise function in the pulmonary microvasculature has remained unclear. In this study, we demonstrate a role for BMP-9 in regulating pulmonary vascular architecture and homeostasis.

Placental growth factor modulates endothelial NO production and exacerbates experimental hepatopulmonary syndrome.

Background & Aims: Hepatopulmonary syndrome (HPS) results from portal hypertension, with or without cirrhosis, and is marked by pulmonary vascular dilations leading to severe hypoxemia. Although placental growth factor (PlGF) is important for vascular growth and endothelial function, its role in HPS is unclear. This study investigated the involvement of PlGF in experimental models of HPS and in patients.

Exploring the Endothelin-1 pathway in chronic thromboembolic pulmonary hypertension microvasculopathy.

Targeted vasopeptide therapies have significantly advanced the management of pulmonary arterial hypertension (PAH). However, due to insufficient preclinical evidence regarding the involvement of the endothelin-1 (ET-1) pathway in chronic thromboembolic pulmonary hypertension (CTEPH) pathophysiology, the potential of ET-1 receptor antagonism in treating CTEPH remains uncertain. In this study, we investigated the role of the ET-1 pathway in CTEPH microvasculopathy using a multifaceted approach.

Effect of sotatercept on circulating proteomics in pulmonary arterial hypertension.

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The Effect of Cuproptosis-Related Proteins on Macrophage Polarization in Mesothelioma is Revealed by scRNA-seq.

High invasiveness mesothelioma is a malignant tumor of the peritoneum or pleura. The effect of cuproptosis on mesothelioma (MESO) is still unknown, though. The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) datasets were used to identify differential genes linked to cuproptosis in mesothelioma.

Eruptive xanthomas in a patient with severe hypertriglyceridemia: A case report.

Background: Xanthomatosis, a metabolic disorder causing yellow growths (xanthomas), poses challenges in lipid metabolism. This case study introduces the first documented instance within China's Yi population, emphasizing the need to explore dietary habits and treatment strategies tailored to this specific community.

Case Summary: Xanthomatosis is a metabolic disorder where lipid metabolism goes awry, resulting in the development of yellowish growths called xanthomas.

Disrupted BMP-9 Signaling Impairs Pulmonary Vascular Integrity in Hepatopulmonary Syndrome.

Hepatopulmonary syndrome (HPS) is a severe complication of liver diseases characterized by abnormal dilation of pulmonary vessels, resulting in impaired oxygenation. Recent research highlights the pivotal role of liver-produced BMP-9 (bone morphogenetic protein-9) in maintaining pulmonary vascular integrity. This study aimed to investigate the involvement of BMP-9 in human and experimental HPS.

NGF increases Connexin-43 expression and function in pulmonary arterial smooth muscle cells to induce pulmonary artery hyperreactivity.

Aims: Pulmonary hypertension (PH) is characterised by an increase in pulmonary arterial pressure, ultimately leading to right ventricular failure and death. We have previously shown that nerve growth factor (NGF) plays a critical role in PH. Our objectives here were to determine whether NGF controls Connexin-43 (Cx43) expression and function in the pulmonary arterial smooth muscle, and whether this mechanism contributes to NGF-induced pulmonary artery hyperreactivity.

Sesquiterpenoids and hexanorcucurbitacin from agarwood with anti-inflammatory effects by inhibiting the STAT1/AKT/MAPK/NLRP3 pathway.

Seven unknown compounds 1-7, including four sesquiterpenoids, one azulene-type, one indene-type, and one rare hexanorcucurbitacin, together with eleven knowns ones (8-16), were isolated from the agarwood chips of . The structures of the isolated compounds were elucidated by extensive spectroscopic methods such as mass spectrometry, UV, IR, NMR spectroscopy. The precise stereo-chemical configurations of new compounds were determined by calculated ECD spectra data, as well as a single-crystal X-ray diffraction analysis.

Role of KCNK3 Dysfunction in Dasatinib-associated Pulmonary Arterial Hypertension and Endothelial Cell Dysfunction.

Pulmonary arterial (PA) hypertension (PAH) is a severe cardiopulmonary disease that may be triggered by exposure to drugs such as dasatinib or facilitated by genetic predispositions. The incidence of dasatinib-associated PAH is estimated at 0.45%, suggesting individual predispositions.

Agarperoxinols A and B: Two Unprecedented Tricyclic 6/6/7 Rearranged Humulene-Type Sesquiterpenoids That Attenuated the Neuroinflammation in LPS-Stimulated Microglial Models.

Agarperoxinols A and B (), two naturally occurring humulene-type sesquiterpenoids with an unprecedented tricyclic 6/6/7 ring, were discovered from the agarwood of . Their structures were unambiguously determined by various spectroscopic data, experimental ECD calculations, and single-crystal X-ray diffraction analysis. Agarperoxinol B showed significant and dose-dependent neuroinflammatory inhibitory effects on various proinflammatory mediators, including NO, TNF-α, IL-6, and IL-1β, and suppressed iNOS and COX-2 enzymes in LPS-activated microglial cells.

Central role of ubiquitin-specific protease 8 in leptin signaling pathway in pulmonary arterial hypertension.

Background: Leptin receptor (ObR-b) is overexpressed in pulmonary artery smooth muscle cells (PA-SMCs) from patients with pulmonary arterial hypertension (PAH) and is implicated in both mechanisms that contribute to pulmonary vascular remodeling: hyperproliferation and inflammation. Our aim was to investigate the role of ubiquitin-specific peptidase 8 (USP8) in ObR-b overexpression in PAH.

Methods: We performed in situ and in vitro experiments in human lung specimens and isolated PA-SMCs combined with 2 different in vivo models in rodents and we generated a mouse with an inducible USP8 deletion specifically in smooth muscles.

Arsenic trioxide demonstrates efficacy in a mouse model of preclinical systemic sclerosis.

Background: Uncontrolled T-cell activation plays a key role in systemic sclerosis (SSc). Arsenic trioxide (ATO) has immunological effects and has demonstrated potential in preclinical SSc models. In this study, we assessed the efficacy of ATO in Fra2 transgenic (Fra2) mice, which develop severe vascular remodeling of pulmonary arterioles and nonspecific interstitial pneumonia-like lung disease, closely resembling human SSc-associated pulmonary hypertension, therefore partially resembling to the SSc human disease.

Effects of B Cell Depletion by CD19-Targeted Chimeric Antigen Receptor T Cells in a Murine Model of Systemic Sclerosis.

Objective: Our goal was to study the tolerance and efficacy of two B cell depletion strategies, including one with CD19-targeted chimeric antigen receptor (CAR) T cells, in a preclinical model mimicking the severe lung damages observed in systemic sclerosis.

Methods: B cell depletion strategies were evaluated in the Fra-2 transgenic (Tg) mouse model. We considered a first group of 16 untreated mice, a second group of 15 mice receiving a single dose of anti-CD20 monoclonal antibody (mAb), and a third group of 8 mice receiving CD19-targeted CAR-T cells in combination with anti-CD20 monoclonal antibody.

Serum and Pulmonary Expression Profiles of the Activin Signaling System in Pulmonary Arterial Hypertension.

Background: Activins are novel therapeutic targets in pulmonary arterial hypertension (PAH). We therefore studied whether key members of the activin pathway could be used as PAH biomarkers.

Methods: Serum levels of activin A, activin B, α-subunit of inhibin A and B proteins, and the antagonists follistatin and follistatin-like 3 (FSTL3) were measured in controls and in patients with newly diagnosed idiopathic, heritable, or anorexigen-associated PAH (n=80) at baseline and 3 to 4 months after treatment initiation.

AMPK activation by metformin protects against pulmonary hypertension in rats and relaxes isolated human pulmonary artery.

Pulmonary hypertension (PH) is associated with pulmonary vasoconstriction and endothelial dysfunction leading to impaired nitric oxide (NO) and prostacyclin (PGI) pathways. Metformin, the first line treatment for type 2 diabetes and AMP-activated protein kinase (AMPK) activator, has been recently highlighted as a potential PH treatment. AMPK activation has been reported to improve endothelial function by enhancing endothelial NO synthase (eNOS) activity and to have relaxant effects in blood vessels.

Inhibition of Soluble Epoxide Hydrolase Does Not Promote or Aggravate Pulmonary Hypertension in Rats.

Inhibitors of soluble epoxide hydrolase (sEH), which catalyzes the hydrolysis of various natural epoxides to their corresponding diols, present an opportunity for developing oral drugs for a range of human cardiovascular and inflammatory diseases, including, among others, diabetes and neuropathic pain. However, some evidence suggests that their administration may precipitate the development of pulmonary hypertension (PH). We thus evaluated the impact of chronic oral administration of the sEH inhibitor TPPU (N-[1-(1-Oxopropyl)-4-piperidinyl]-N'-[4-(trifluoromethoxy)phenyl]-urea) on hemodynamics, pulmonary vascular reactivity, and remodeling, as well as on right ventricular (RV) dimension and function at baseline and in the Sugen (SU5416) + hypoxia (SuHx) rat model of severe PH.

Biomarkers of haemodynamic severity of systemic sclerosis-associated pulmonary arterial hypertension by serum proteome analysis.

Objectives: To mine the serum proteome of patients with systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) and to detect biomarkers that may assist in earlier and more effective diagnosis and treatment.

Methods: Patients with limited cutaneous SSc, no extensive interstitial lung disease and no PAH-specific therapy were included. They were classified as cases if they had PAH confirmed by right heart catheterisation (RHC) and serum collected on the same day as RHC; and as controls if they had no clinical evidence of PAH.

Cytokines as prognostic biomarkers in pulmonary arterial hypertension.

Background: Risk stratification and assessment of disease progression in patients with pulmonary arterial hypertension (PAH) are challenged by the lack of accurate disease-specific and prognostic biomarkers. To date, brain natriuretic peptide (BNP) and/or its N-terminal fragment (NT-proBNP) are the only markers for right ventricular dysfunction used in clinical practice, in association with echocardiographic and invasive haemodynamic variables to predict outcome in patients with PAH.

Methods: This study was designed to identify an easily measurable biomarker panel in the serum of 80 well-phenotyped PAH patients with idiopathic, heritable or drug-induced PAH at baseline and at first follow-up.

Mineralocorticoid Receptor Antagonism by Finerenone Attenuates Established Pulmonary Hypertension in Rats.

Background: We studied the ability of the nonsteroidal MR (mineralocorticoid receptor) antagonist finerenone to attenuate vascular remodeling and pulmonary hypertension using two complementary preclinical models (the monocrotaline and sugen/hypoxia rat models) of severe pulmonary hypertension.

Methods: We first examined the distribution pattern of MR in the lungs of patients with pulmonary arterial hypertension (PAH) and in monocrotaline and sugen/hypoxia rat lungs. Subsequent studies were performed to explore the effect of MR inhibition on proliferation of pulmonary artery smooth muscle cells derived from patients with idiopathic PAH.

Kynurenine metabolites predict survival in pulmonary arterial hypertension: A role for IL-6/IL-6Rα.

Activation of the kynurenine pathway (KP) has been reported in patients with pulmonary arterial hypertension (PAH) undergoing PAH therapy. We aimed to determine KP-metabolism in treatment-naïve PAH patients, investigate its prognostic values, evaluate the effect of PAH therapy on KP-metabolites and identify cytokines responsible for altered KP-metabolism. KP-metabolite levels were determined in plasma from PAH patients (median follow-up 42 months) and in rats with monocrotaline- and Sugen/hypoxia-induced PH.