Am J Physiol Lung Cell Mol Physiol
March 2024
Pulmonary arterial hypertension (PAH) is a morbid disease characterized by significant lung endothelial cell (EC) dysfunction. Prior work has shown that microvascular endothelial cells (MVECs) isolated from animals with experimental PAH and patients with PAH exhibit significant abnormalities in metabolism and calcium signaling. With regards to metabolism, we and others have shown evidence of increased aerobic glycolysis and evidence of increased utilization of alternate fuel sources (such as fatty acids) in PAH EC.
View Article and Find Full Text PDFRelationships between obesity and outcomes in pulmonary arterial hypertension (PAH) are complex. Previous work suggested obesity, occurring alongside PAH, may be associated with better survival. In our work, we suggest obesity prior to PAH development is associated with worse survival.
View Article and Find Full Text PDFCatheter Cardiovasc Interv
January 2024
We present the case of a 28-year-old woman with a history of tricuspid valve endocarditis leading to chronic thromboembolic pulmonary hypertension (CTEPH) with multiple pulmonary artery chronic total occlusions (CTOs) due to septic emboli. Following a multidisciplinary care discussion, the patient was brought forward for balloon pulmonary angioplasty (BPA) with successful revascularization of all chronically occluded territories. This case highlights advances in pulmonary artery CTO interventions and demonstrates the feasibility of BPA for CTEPH patients with a history of septic emboli.
View Article and Find Full Text PDFPulmonary arterial hypertension (PAH) is a heterogeneous disease within a complex diagnostic and treatment environment. Other complex heart and lung diseases have substantial regional variation in characteristics and outcomes; however, this has not been previously described in PAH. To identify baseline differences between U.
View Article and Find Full Text PDFIntroduction: Balloon pulmonary angioplasty (BPA) is a less invasive treatment alternative for patients with chronic thromboembolic pulmonary hypertension (CTEPH) who are unable to move forward with pulmonary thromboendarterectomy. This report describes a single-center experience with a nascent BPA program in the United States (US).
Methods: All patients who underwent BPA between August 2018-2021 were included in this retrospective, single-center observational cohort.
In pulmonary artery hypertension (PAH), emerging evidence suggests that metabolic abnormalities may be contributing to cellular dysfunction in PAH. Metabolic abnormalities such as glycolytic shift have been observed intracellularly in several cell types in PAH, including microvacular endothelial cells (MVECs). Concurrently, metabolomics of human PAH samples has also revealed a variety of metabolic abnormalities; however the relationship between the intracellular metabolic abnormalities and the serum metabolome in PAH remains under investigation.
View Article and Find Full Text PDFBackground: Pulmonary arterial hypertension (PAH) is a complex disease characterized by progressive right ventricular (RV) failure leading to significant morbidity and mortality. Investigating metabolic features and pathways associated with RV dilation, mortality, and measures of disease severity can provide insight into molecular mechanisms, identify subphenotypes, and suggest potential therapeutic targets.
Methods: We collected data from a prospective cohort of PAH participants and performed untargeted metabolomic profiling on 1045 metabolites from circulating blood.
Context: Physicians who specialize in pulmonary arterial hypertension (PAH) care for patients facing a serious, life-limiting illness. Palliative care is underutilized in patients with PAH, and little is known about how best to provide palliative care to this patient population.
Objectives: Using a qualitative approach, assess physicians' perspectives on barriers and facilitators to the use of palliative care in PAH.
Background: Subtypes of pulmonary arterial hypertension (PAH) differ in both fundamental disease features and clinical outcomes. Angiogenesis and inflammation represent disease features that may differ across subtypes and are of special interest in connective tissue disease-associated PAH (CTD-PAH). We compared inflammatory and angiogenic biomarker profiles across different etiologies of PAH and related them to clinical outcomes.
View Article and Find Full Text PDFStem cell division is linked to tumorigenesis by yet-elusive mechanisms. The hematopoietic system reacts to stress by triggering hematopoietic stem and progenitor cell (HSPC) proliferation, which can be accompanied by chromosomal breakage in activated hematopoietic stem cells (HSCs). However, whether these lesions persist in their downstream progeny and induce a canonical DNA damage response (DDR) remains unclear.
View Article and Find Full Text PDFIntroduction: Pulmonary arterial hypertension (PAH) remains a serious and life-threatening illness. Thyroid dysfunction is relatively understudied in individuals with PAH but is known to affect cardiac function and vascular tone in other diseases. The aim of this observational study was to evaluate the association between thyroid-stimulating hormone (TSH), mortal and non-mortal outcomes in individuals with PAH.
View Article and Find Full Text PDFPulmonary arterial hypertension (PAH) is characterized by increased resistance in the pulmonary arterioles as a result of remodeled blood vessels. We sought all available epidemiologic data on population-based prevalence, incidence, and 1-year survival of PAH as part of the Global Burden of Disease Study. We performed a systematic review searching Global Index Medicus (GIM) for keywords related to PAH between 1980 and 2021 and identified population-representative sources of prevalence, incidence, and mortality for clinically diagnosed PAH.
View Article and Find Full Text PDFBackground: Von Willebrand factor (VWF) is classically associated with primary hemostasis and platelet-rich arterial thromboses, but recently has also been implicated in fibrin clotting and venous thrombosis. Direct interaction between fibrin and VWF may mediate these processes, although prior reports are conflicting.
Objectives: We combined two complementary platforms to characterize VWF-fibrin(ogen) interactions and identify their potential physiologic significance.
Background Prior studies suggested lower risk of heart failure (HF) in individuals taking H receptor antagonists (H2RA) compared with H2RA nonusers in relatively small studies. We evaluated the association of H2RA use and incident HF in postmenopausal women in the large-scale WHI (Women's Health Initiative) study. Methods and Results This study included postmenopausal women from the WHI without a history of HF at baseline.
View Article and Find Full Text PDFBackground: Soluble Fms-like tyrosine kinase 1 (sFlt-1) may inhibit angiogenesis. Higher levels of sFlt-1 are associated with worse prognosis in prevalent heart failure patients. The aim of this study was to better understand the role of sFlt-1 in heart failure pathogenesis by characterizing relationships between sFlt-1, cardiac morphology, and the composite outcome of incident heart failure or cardiovascular (CV) death in in a multiethnic cohort free of CV disease at baseline.
View Article and Find Full Text PDFNumerous targeted therapies have been developed for diffuse large B-cell lymphoma, but the results of late-stage clinical trials were mostly disappointing and have led to very few new regulatory approvals. Here, we use single and combinatorial drug response profiling to show that the combined inhibition of the anti-apoptotic protein Bcl-2 and of the tyrosine kinase BTK with the small molecules venetoclax and ibrutinib efficiently kills DLBCL cells in vitro. High Bcl-2 expression due to either BCL2 amplifications or translocations, in conjunction with chronic active BCR signaling accurately predict responses to dual Bcl-2/BTK inhibition.
View Article and Find Full Text PDFHeart failure with preserved ejection fraction (HFpEF) is the most common form of heart failure and frequently is associated with pulmonary hypertension (PH). HFpEF associated with PH may be difficult to distinguish from precapillary forms of PH, although this distinction is crucial because therapeutic pathways are divergent for the two conditions. A comprehensive and systematic approach using history, clinical examination, and noninvasive and invasive evaluation with and without provocative testing may be necessary for accurate diagnosis and phenotyping.
View Article and Find Full Text PDF