Store-operated Ca entry is involved in endothelium-to-mesenchymal transition in lung vascular endothelial cells.

Unlabelled: Endothelial-to-mesenchymal transition (EndMT) is a biological process that converts endothelial cells to mesenchymal cells with increased proliferative and migrative abilities. EndMT has been implicated in the development of pulmonary vascular remodeling in pulmonary arterial hypertension (PAH), a fatal and progressive lung vascular disease. Transforming growth factor β (TGF-β ), an inflammatory cytokine, is known to induce EndMT in many types of endothelial cells including lung vascular endothelial cells (LVEC).

Tricuspid annular plane systolic excursion to pulmonary artery systolic pressure ratio in chronic thromboembolic pulmonary hypertension improves with balloon pulmonary angioplasty.

Right ventricle (RV)-to-pulmonary artery (PA) coupling measured by the ratio of echocardiography-derived tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PASP) is a meaningful prognostic marker in pulmonary hypertension (PH). It's unclear if balloon pulmonary angioplasty (BPA) treatment of chronic thromboembolic pulmonary hypertension (CTEPH) alters RV-PA coupling measured by TAPSE/PASP. We reviewed CTEPH patients treated with BPA at our institution who had a transthoracic echocardiogram (TTE) before BPA and a follow-up TTE at any point during BPA.

Circulating dimethylguanidino valeric acid, dietary factors, and risk of coronary heart disease.

Aims: Circulating dimethylguanidino valeric acid (DMGV) was identified as a novel metabolite related to cardiorespiratory fitness and cardiometabolic abnormalities. Circulating DMGV levels are subjective to dietary modulation; however, studies on its associations with intakes of coronary heart disease (CHD)-related foods/nutrients are limited. We investigated whether plasma DMGV was related to risk of incident CHD.

Plasma Levels of Polyols Erythritol, Mannitol, and Sorbitol and Incident Coronary Heart Disease Among Women.

Background And Aims: Erythritol, a sugar alcohol (polyol), has recently been linked to the risks of major adverse cardiovascular events. We investigated whether plasma erythritol and other polyols (mannitol/sorbitol) were associated with the risk of incident coronary heart disease (CHD).

Methods: This prospective nested case-control study included 762 incident cases of CHD and 762 controls from the Nurses' Health Study.

Genetics and precision genomics approaches to pulmonary hypertension.

Considerable progress has been made in the genomics of pulmonary arterial hypertension (PAH) since the 6th World Symposium on Pulmonary Hypertension, with the identification of rare variants in several novel genes, as well as common variants that confer a modest increase in PAH risk. Gene and variant curation by an expert panel now provides a robust framework for knowing which genes to test and how to interpret variants in clinical practice. We recommend that genetic testing be offered to specific subgroups of symptomatic patients with PAH, and to children with certain types of group 3 pulmonary hypertension (PH).

Gut-Microbiota-Related Metabolite Phenylacetylglutamine and Risk of Incident Coronary Heart Disease among Women.

Context: Phenylacetylglutamine (PAGln) is a novel metabolite derived from gut microbial metabolism of dietary proteins, specifically phenylalanine, which may be linked to risks of adverse cardiovascular events.

Objective: We investigated whether higher plasma levels of PAGln were associated with a greater risk of incident coronary heart disease (CHD) and tested whether adherence to a plant-based diet, which characterizes habitual dietary patterns of animal and plant food intake, modified the associations.

Methods: We examined associations between plasma PAGln and risk of incident CHD over 11-16 years in a nested case-control study of 1520 women (760 incident cases and 760 controls) from the Nurses' Health Study.

One-Year Effects of High-Intensity Statin on Bioactive Lipids: Findings From the JUPITER Trial.

Background: Statin effects extend beyond low-density lipoprotein cholesterol reduction, potentially modulating the metabolism of bioactive lipids (BALs), crucial for biological signaling and inflammation. These bioactive metabolites may serve as metabolic footprints, helping uncover underlying processes linked to pleiotropic effects of statins and yielding a better understanding of their cardioprotective properties. This study aimed to investigate the impact of high-intensity statin therapy versus placebo on plasma BALs in the JUPITER trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin; NCT00239681), a randomized primary prevention trial involving individuals with low-density lipoprotein cholesterol <130 mg/dL and high-sensitivity C-reactive protein ≥2 mg/L.

Genome-wide association study reveals shared and distinct genetic architecture underlying fatty acid and bioactive oxylipin metabolites in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

Bioactive fatty acid-derived oxylipin molecules play key roles in mediating inflammation and oxidative stress, which underlie many chronic diseases. Circulating levels of fatty acids and oxylipins are influenced by both environmental and genetic factors; characterizing the genetic architecture of bioactive lipids could yield new insights into underlying biological pathways. Thus, we performed a genome wide association study (GWAS) of n=81 fatty acids and oxylipins in n=11,584 Hispanic Community Health Study/Study of Latinos (HCHS/SOL) participants with genetic and lipidomic data measured at study baseline (58.

NT-pro-BNP is predictive of morbidity and mortality after pulmonary thromboendarterectomy and is independent of preoperative hemodynamics.

Current predictors of clinical outcomes after pulmonary thromboendarterectomy (PTE) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) are largely limited to preoperative clinical characteristics. N-terminal-pro-brain natriuretic peptide (NT-pro-BNP), a biomarker of right ventricular dysfunction, has not yet been well described as one such predictor. From 2017 to 2021, 816 patients with CTEPH referred to the University of California, San Diego for PTE were reviewed for differences in NT-pro-BNP to predict preoperative characteristics and postoperative outcomes up to 30 days post-PTE.

Cardiopulmonary exercise test to detect cardiac dysfunction from pulmonary vascular disease.

Background: Cardiac dysfunction from pulmonary vascular disease causes characteristic findings on cardiopulmonary exercise testing (CPET). We tested the accuracy of CPET for detecting inadequate stroke volume (SV) augmentation during exercise, a pivotal manifestation of cardiac limitation in patients with pulmonary vascular disease.

Methods: We reviewed patients with suspected pulmonary vascular disease in whom CPET and right heart catheterization (RHC) measurements were taken at rest and at anaerobic threshold (AT).

Functional / missense variant is associated with hematocrit in Andean highlanders.

Hypoxia-inducible factor pathway genes are linked to adaptation in both human and nonhuman highland species. , a notable target of hypoxia adaptation, is associated with relatively lower hemoglobin concentration in Tibetans. We provide evidence for an association between an adaptive variant (rs570553380) and the same phenotype of relatively low hematocrit in Andean highlanders.

Pulmonary primary oxysterol and bile acid synthesis as a predictor of outcomes in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a rare and fatal vascular disease with heterogeneous clinical manifestations. To date, molecular determinants underlying the development of PAH and related outcomes remain poorly understood. Herein, we identify pulmonary primary oxysterol and bile acid synthesis (PPOBAS) as a previously unrecognized pathway central to PAH pathophysiology.

Eicosanoid and eicosanoid-related inflammatory mediators and exercise intolerance in heart failure with preserved ejection fraction.

Systemic inflammation has been implicated in the pathobiology of heart failure with preserved ejection fraction (HFpEF). Here, we examine the association of upstream mediators of inflammation as ascertained by fatty-acid derived eicosanoid and eicosanoid-related metabolites with HFpEF status and exercise manifestations of HFpEF. Among 510 participants with chronic dyspnea and preserved LVEF who underwent invasive cardiopulmonary exercise testing, we find that 70 of 890 eicosanoid and related metabolites are associated with HFpEF status, including 17 named and 53 putative eicosanoids (FDR q-value < 0.

Observational cohort study to validate SEARCH, a novel hierarchical algorithm to define long-term outcomes after pulmonary embolism.

Background: Chronic dyspnoea and exercise impairment are common after acute pulmonary embolism (PE) but are not defined and quantified sufficiently to serve as outcomes in clinical trials. The planned project will clinically validate a novel method to determine discrete, clinically meaningful diagnoses after acute PE. The method uses an algorithm entitled SEARCH, for ymptom screen, xercise testing, rterial perfusion, esting echocardiography, onfirmatory imaging and aemodynamic measurements.

Deriving Convergent and Divergent Metabolomic Correlates of Pulmonary Arterial Hypertension.

High-dimensional metabolomics analyses may identify convergent and divergent markers, potentially representing aligned or orthogonal disease pathways that underly conditions such as pulmonary arterial hypertension (PAH). Using a comprehensive PAH metabolomics dataset, we applied six different conventional and statistical learning techniques to identify analytes associated with key outcomes and compared the results. We found that certain conventional techniques, such as Bonferroni/FDR correction, prioritized metabolites that tended to be highly intercorrelated.

Distal vessel pulmonary thromboendarterectomy: Results from a single institution.

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is primarily managed by pulmonary thromboendarterectomy (PTE). As advanced surgical techniques permit resection at the segmental and subsegmental level, PTE can now be curative for CTEPH mostly involving the distal pulmonary arteries.

Methods: Between January 2017 and June 2021, consecutive patients undergoing PTE were categorized according to the most proximal level of chronic thrombus resection: Level I (main pulmonary artery), Level II (lobar), Level III (segmental) and Level IV (subsegmental).

SOX17 Deficiency Mediates Pulmonary Hypertension: At the Crossroads of Sex, Metabolism, and Genetics.

Genetic studies suggest that SOX17 (SRY-related HMG-box 17) deficiency increases pulmonary arterial hypertension (PAH) risk. On the basis of pathological roles of estrogen and HIF2α (hypoxia-inducible factor 2α) signaling in pulmonary artery endothelial cells (PAECs), we hypothesized that SOX17 is a target of estrogen signaling that promotes mitochondrial function and attenuates PAH development via HIF2α inhibition. We used metabolic (Seahorse) and promoter luciferase assays in PAECs together with the chronic hypoxia murine model to test the hypothesis.

The association between eicosanoids and incident atrial fibrillation in the Framingham Heart Study.

Chronic inflammation is a continuous low-grade activation of the systemic immune response. Whereas downstream inflammatory markers are associated with atrial fibrillation (AF), upstream inflammatory effectors including eicosanoids are less studied. To examine the association between eicosanoids and incident AF.

Right Ventricular and Pulmonary Computed Tomography Assessments in Paradoxical Low-Flow Low-Gradient Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement.

Background: Patients with paradoxical low-flow low-gradient aortic stenosis (pLFLG-AS) have high mortality and high degree of TAVR futility. Computed tomography (CT) enables accurate simultaneous right ventricular (RV) and parenchymal lung disease evaluation which may provide useful objective markers of AS severity, concomitant pulmonary comorbidities, and transcatheter aortic valve replacement (TAVR) improvement. However, the prevalence of RV dysfunction and its association with pulmonary disease in pLFLG-AS is unknown.