Extracellular Release of Mitochondrial DNA: Triggered by Cigarette Smoke and Detected in COPD.

Cigarette smoke (CS) is the most common risk factor for chronic obstructive pulmonary disease (COPD). The present study aimed to elucidate whether mtDNA is released upon CS exposure and is detected in the plasma of former smokers affected by COPD as a possible consequence of airway damage. We measured cell-free mtDNA (cf-mtDNA) and nuclear DNA (cf-nDNA) in COPD patient plasma and mouse serum with CS-induced emphysema.

Noncanonical HIPPO/MST Signaling via BUB3 and FOXO Drives Pulmonary Vascular Cell Growth and Survival.

Rationale: The MSTs (mammalian Ste20-like kinases) 1/2 are members of the HIPPO pathway that act as growth suppressors in adult proliferative diseases. Pulmonary arterial hypertension (PAH) manifests by increased proliferation and survival of pulmonary vascular cells in small PAs, pulmonary vascular remodeling, and the rise of pulmonary arterial pressure. The role of MST1/2 in PAH is currently unknown.

Galectin-3 as a Novel Multifaceted and Not Only Cardiovascular Biomarker in Patients with Psoriasis with Regard to Systemic Treatment-Preliminary Data.

Galectin-3 (gal-3) is a multifunctional regulator of various biological processes and diseases, which are common comorbidities in psoriasis. Data regarding potential diagnostic role of gal-3 in psoriasis are insufficient. Serum gal-3 levels were evaluated before and after twelve weeks of treatment with acitretin or methotrexate in 31 patients with plaque-type psoriasis and compared to 11 healthy control group.

Intravital imaging reveals inflammation as a dominant pathophysiology of age-related hepatovascular changes.

Aging is the most significant risk factor for the majority of chronic diseases, including liver disease. The cellular, molecular, and pathophysiological mechanisms that promote age-induced hepatovascular changes are unknown due to our inability to visualize changes in liver pathophysiology in live mice over time. We performed quantitative liver intravital microscopy (qLIM) in live C57BL/6J mice to investigate the impact of aging on the hepatovascular system over a 24-mo period.

Pulmonary Arterial Hypertension: Emerging Principles of Precision Medicine across Basic Science to Clinical Practice.

Pulmonary arterial hypertension (PAH) is an enigmatic and deadly vascular disease with no known cure. Recent years have seen rapid advances in our understanding of the molecular underpinnings of PAH, with an expanding knowledge of the molecular, cellular, and systems-level drivers of disease that are being translated into novel therapeutic modalities. Simultaneous advances in clinical technology have led to a growing list of tools with potential application to diagnosis and phenotyping.

Assessment of Life Quality, Stress and Physical Activity Among Patients with Psoriasis.

Introduction: Psoriasis is a chronic, autoimmune, inflammatory skin disease affecting 2-4% of the general population, which nowadays is even perceived as a systemic illness. The nature of this dermatosis may negatively influence patients' general condition, life expectancy, and quality of life, which highlights the severity of the problem and the need to perform further investigation. We aimed to assess quality of life, stress severity, and physical activity of patients with psoriasis in relation to demographic and clinical data and comparison to the control group without dermatoses.

Circulating MAdCAM-1 and ITGB7 in Patients with Plaque Psoriasis and Eruptive Lichen Planus-Preliminary Data.

Plaque psoriasis (PSO) and lichen planus (LP) are skin diseases with some similarities in pathogenesis, comorbidities, and clinical presentation. Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) and its ligand, αβ integrin, are involved in inflammatory bowel diseases and liver dysfunctions, which occur more frequently in PSO and LP. Serum MAdCAM-1 and ITGB7 levels in patients with plaque PSO and eruptive LP have never been studied before.

PGC1α Regulates the Endothelial Response to Fluid Shear Stress via Telomerase Reverse Transcriptase Control of Heme Oxygenase-1.

Objective: Fluid shear stress (FSS) is known to mediate multiple phenotypic changes in the endothelium. Laminar FSS (undisturbed flow) is known to promote endothelial alignment to flow, which is key to stabilizing the endothelium and rendering it resistant to atherosclerosis and thrombosis. The molecular pathways responsible for endothelial responses to FSS are only partially understood.

Intravital Imaging of Hepatic Blood Biliary Barrier in Live Mice.

Understanding the kinetics and spatiotemporal interactions of living cells within the tissue environment requires real-time imaging. The introduction of two-photon microscopy has substantially boosted the power of live intravital imaging, making it possible to obtain information of individual cells in near-physiologic conditions within intact tissues nondestructively. Intravital imaging of the liver has proved useful in understanding its 3D structure, function, and dynamic cellular interactions.

Medial Arterial Calcification: JACC State-of-the-Art Review.

Medial arterial calcification (MAC) is a chronic systemic vascular disorder distinct from atherosclerosis that is frequently but not always associated with diabetes mellitus, chronic kidney disease, and aging. MAC is also a part of more complex phenotypes in numerous less common diseases. The hallmarks of MAC include disseminated and progressive precipitation of calcium phosphate within the medial layer, a prolonged and clinically silent course, and compromise of hemodynamics associated with chronic limb-threatening ischemia.

Vascepa protects against high-fat diet-induced glucose intolerance, insulin resistance, and impaired β-cell function.

Omega-3 fatty acid prescription drugs, Vascepa (≥96% eicosapentaenoic acid [EPA] ethyl ester) and Lovaza (46.5% EPA and 37.5% docosahexaenoic acid ethyl ester) are known therapeutic regimens to treat hypertriglyceridemia.

Recent advancements in pulmonary arterial hypertension and right heart failure research: overview of selected abstracts from ATS2020 and emerging COVID-19 research.

Each year the American Thoracic Society (ATS) Conference brings together scientists who conduct basic, translational and clinical research to present on the recent advances in the field of respirology. Due to the Coronavirus Disease of 2019 (COVID-19) pandemic, the ATS2020 Conference was held online in a series of virtual meetings. In this review, we focus on the breakthroughs in pulmonary hypertension research.

The ubiquitous mitochondrial protein unfoldase CLPX regulates erythroid heme synthesis by control of iron utilization and heme synthesis enzyme activation and turnover.

Heme plays a critical role in catalyzing life-essential redox reactions in all cells, and its synthesis must be tightly balanced with cellular requirements. Heme synthesis in eukaryotes is tightly regulated by the mitochondrial AAA+ unfoldase CLPX (caseinolytic mitochondrial matrix peptidase chaperone subunit X), which promotes heme synthesis by activation of δ-aminolevulinate synthase (ALAS/Hem1) in yeast and regulates turnover of ALAS1 in human cells. However, the specific mechanisms by which CLPX regulates heme synthesis are unclear.

Yes-Associated Protein (Yap) Is Up-Regulated in Heart Failure and Promotes Cardiac Fibroblast Proliferation.

Left ventricular (LV) heart failure (HF) is a significant and increasing cause of death worldwide. HF is characterized by myocardial remodeling and excessive fibrosis. Transcriptional co-activator Yes-associated protein (Yap), the downstream effector of HIPPO signaling pathway, is an essential factor in cardiomyocyte survival; however, its status in human LV HF is not entirely elucidated.

Metabolic Syndrome Mediates ROS-miR-193b-NFYA-Dependent Downregulation of Soluble Guanylate Cyclase and Contributes to Exercise-Induced Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction.

Background: Many patients with heart failure with preserved ejection fraction have metabolic syndrome and develop exercise-induced pulmonary hypertension (EIPH). Increases in pulmonary vascular resistance in patients with heart failure with preserved ejection fraction portend a poor prognosis; this phenotype is referred to as combined precapillary and postcapillary pulmonary hypertension (CpcPH). Therapeutic trials for EIPH and CpcPH have been disappointing, suggesting the need for strategies that target upstream mechanisms of disease.

Simultaneous Pharmacologic Inhibition of Yes-Associated Protein 1 and Glutaminase 1 via Inhaled Poly(Lactic-co-Glycolic) Acid-Encapsulated Microparticles Improves Pulmonary Hypertension.

Background Pulmonary hypertension (PH) is a deadly disease characterized by vascular stiffness and altered cellular metabolism. Current treatments focus on vasodilation and not other root causes of pathogenesis. Previously, it was demonstrated that glutamine metabolism, as catalyzed by GLS1 (glutaminase 1) activity, is mechanoactivated by matrix stiffening and the transcriptional coactivators YAP1 (yes-associated protein 1) and transcriptional coactivator with PDZ-binding motif (TAZ), resulting in pulmonary vascular proliferation and PH.

Multiple-ancestry genome-wide association study identifies 27 loci associated with measures of hemolysis following blood storage.

BackgroundThe evolutionary pressure of endemic malaria and other erythrocytic pathogens has shaped variation in genes encoding erythrocyte structural and functional proteins, influencing responses to hemolytic stress during transfusion and disease.MethodsWe sought to identify such genetic variants in blood donors by conducting a genome-wide association study (GWAS) of 12,353 volunteer donors, including 1,406 African Americans, 1,306 Asians, and 945 Hispanics, whose stored erythrocytes were characterized by quantitative assays of in vitro osmotic, oxidative, and cold-storage hemolysis.ResultsGWAS revealed 27 significant loci (P < 5 × 10-8), many in candidate genes known to modulate erythrocyte structure, metabolism, and ion channels, including SPTA1, ALDH2, ANK1, HK1, MAPKAPK5, AQP1, PIEZO1, and SLC4A1/band 3.

Electrophilic nitro-fatty acids suppress psoriasiform dermatitis: STAT3 inhibition as a contributory mechanism.

Psoriasis is a chronic inflammatory skin disease with no cure. Although the origin of psoriasis and its underlying pathophysiology remain incompletely understood, inflammation is a central mediator of disease progression. In this regard, electrophilic nitro-fatty acids (NO-FAs) exert potent anti-inflammatory effects in several in vivo murine models of inflammatory diseases, such as chronic kidney disease and cardiovascular disease.

Isolation of Human Primary Valve Cells for In vitro Disease Modeling.

Calcific aortic valve disease (CAVD) is present in nearly a third of the elderly population. Thickening, stiffening, and calcification of the aortic valve causes aortic stenosis and contributes to heart failure and stroke. Disease pathogenesis is multifactorial, and stresses such as inflammation, extracellular matrix remodeling, turbulent flow, and mechanical stress and strain contribute to the osteogenic differentiation of valve endothelial and valve interstitial cells.

Caveolar peroxynitrite formation impairs endothelial TRPV4 channels and elevates pulmonary arterial pressure in pulmonary hypertension.

Recent studies have focused on the contribution of capillary endothelial TRPV4 channels to pulmonary pathologies, including lung edema and lung injury. However, in pulmonary hypertension (PH), small pulmonary arteries are the focus of the pathology, and endothelial TRPV4 channels in this crucial anatomy remain unexplored in PH. Here, we provide evidence that TRPV4 channels in endothelial cell caveolae maintain a low pulmonary arterial pressure under normal conditions.