Explanipedia

Endothelial ENaC as a repressor of oxidative stress and a guardian of lung capillary barrier function in bacterial and viral pneumonia Open

Douglas C. Eaton, Maritza J. Romero, Michael A. Matthay, Jürg Hamacher, Andrew Advani , et al. · 2025

The endothelium represents a crucial regulator of vascular homeostasis. Since endothelial cells mainly rely on glycolysis rather than on oxidative phosphorylation for their ATP generation, this allows capillaries to transport the maximum a…

PFKFB3 Connects Glycolytic Metabolism with Endothelial Dysfunction in Human and Rodent Obesity Open

Róbert Bátori, Zsuzsanna Bordán, Caleb A. Padgett, Yuqing Huo, Feng Chen , et al. · 2025

Obesity and type 2 diabetes (T2D) increase cardiovascular risk, largely due to altered metabolic state. An early consequence of T2D/obesity is the loss of endothelial function and impaired nitric oxide (NO) signaling. In blood vessels, end…

Endothelial Drp1 Couples VEGF-induced Redox Signaling with Glycolysis Through Cysteine Oxidation to Drive Angiogenesis Open

Masuko Ushio‐Fukai, Sheela Nagarkoti, Young-Mee Kim, Archita Das, Dipankar Ash , et al. · 2024

Angiogenesis plays a vital role for postnatal development and tissue repair following ischemia. Reactive oxygen species (ROS) generated by NADPH oxidases (NOXes) and mitochondria act as signaling molecules that promote angiogenesis in endo…

PDZ-Binding Kinase, a Novel Regulator of Vascular Remodeling in Pulmonary Arterial Hypertension Open

Zsuzsanna Bordán, Róbert Bátori, Stephen Haigh, Xueyi Li, Mary Louise Meadows , et al. · 2024

BACKGROUND: Pulmonary arterial hypertension (PAH) is high blood pressure in the lungs that originates from structural changes in small resistance arteries. A defining feature of PAH is the inappropriate remodeling of pulmonary arteries (PA…

NADPH oxidase 1 promotes hepatic steatosis in obese mice and is abrogated by augmented skeletal muscle mass Open

Sebastian Larion, Caleb A. Padgett, James Mintz, Jennifer Thompson, Joshua T. Butcher , et al. · 2024

This study documents a novel mechanism by which changes in body composition, notably increased muscle mass, protect against fatty liver disease. This mechanism involves NADPH oxidase 1 (NOX1), an enzyme that increases superoxide and increa…

289 Beyond SION-638: a novel series of highly potent stabilizers of the first nucleotide binding domain enables full correction of ΔF508-CFTR in a dual combination with Sionna CFTR modulators, providing a path to wild-type function Open

G. Hurlbut, S. Altmann, M. Barrague, S. Bercury, M. Duguid , et al. · 2023

A Reappraisal of the Utility of L-012 to Measure Superoxide from Biologically Relevant Sources Open

Stephen Haigh, Zachary Brown, Mitch Shivers, Hunter Sellers, Madison A. West , et al. · 2023

The detection of superoxide anion (O2●−) in biological tissues remains challenging. Barriers to convenient and reproducible measurements include expensive equipment, custom probes, and the need for high sensitivity and specificity. The lum…

Galectin-3 Mediates Vascular Dysfunction in Obesity by Regulating NADPH Oxidase 1 Open

Caleb A. Padgett, Róbert Bátori, Andrew C. Speese, Cody L. Rosewater, Weston B. Bush , et al. · 2023

BACKGROUND: Obesity is associated with increased risk of cardiovascular disease, but underlying mechanisms remain elusive. Metabolic dysfunction, especially hyperglycemia, is thought to be a major contributor, but how glucose impacts vascu…

EPS3.10 Novel CFTR modulator combinations directly address the ΔF508-CFTR NBD1 stability defect and enable full CFTR correction Open

G. Hurlbut, S. Altmann, M. Barrague, S. Bercury, M. Duguid , et al. · 2023

Early Endothelial Dysfunction in a Novel Model of Sustained Hyperphagia and Obesity in Mice Using a Brain Targeting Adeno-Associated Virus Open

Hunter Sellers, Caleb A. Padgett, James Mintz, Andrew C. Speese, Zachary Brown , et al. · 2023

Galectin-3 Mediates Vascular Dysfunction in Obesity by Regulating NADPH Oxidase 1 Open

Caleb A. Padgett, Róbert Bátori, Andrew C. Speese, Cody Rosewater, Weston B. Bush , et al. · 2023

Rationale Obesity increases the risk of cardiovascular disease (CVD) through mechanisms that remain incompletely defined. Metabolic dysfunction, especially hyperglycemia, is thought to be a major contributor but how glucose impacts vascula…

The Long Noncoding RNA Cardiac Mesoderm Enhancer-Associated Noncoding RNA (Carmn) Is a Critical Regulator of Gastrointestinal Smooth Muscle Contractile Function and Motility Open

Xiangqin He, Kunzhe Dong, Jian Shen, Guoqing Hu, James Mintz , et al. · 2023

Perivascular adipose tissue promotes vascular dysfunction in murine lupus Open

Hong Shi, Brandee Goo, David Kim, Taylor C. Kress, Mourad Ogbi , et al. · 2023

Introduction Patients with systemic lupus erythematosus (SLE) are at elevated risk for Q10 cardiovascular disease (CVD) due to accelerated atherosclerosis. Compared to heathy control subjects, lupus patients have higher volumes and densiti…

Strong methane point sources contribute a disproportionate fraction of total emissions across multiple basins in the United States Open

Daniel Cusworth, Andrew K. Thorpe, Alana Ayasse, David W. Stepp, Joseph Heckler , et al. · 2022

Understanding, prioritizing, and mitigating methane (CH 4 ) emissions requires quantifying CH 4 budgets from facility scales to regional scales with the ability to differentiate between source sectors. We deployed a tiered observing system…

The biological clock enhancer nobiletin ameliorates steatosis in genetically obese mice by restoring aberrant hepatic circadian rhythm Open

Sebastian Larion, Caleb A. Padgett, Joshua T. Butcher, James Mintz, David Fulton , et al. · 2022

NAFLD is the most common chronic liver disease, but underlying mechanisms are unclear. We show here that genetically obese ( db/db) mice with fatty liver have impaired hepatic circadian rhythm. Hepatic Per2 expression and PER2 reporter act…

Protective role of Cav-1 in pneumolysin-induced endothelial barrier dysfunction Open

Róbert Bátori, Feng Chen, Zsuzsanna Bordán, Stephen Haigh, Yunchao Su , et al. · 2022

Pneumolysin (PLY) is a bacterial pore forming toxin and primary virulence factor of Streptococcus pneumonia , a major cause of pneumonia. PLY binds cholesterol-rich domains of the endothelial cell (EC) plasma membrane resulting in pore ass…

The LncRNA <i>Carmn</i> is a Critical Regulator for Gastrointestinal Smooth Muscle Contractile Function and Motility Open

Xiangqin He, Kunzhe Dong, Jian Shen, Guoqing Hu, James Mintz , et al. · 2022

Background & aims Visceral smooth muscle cells (SMCs) are an integral component of the gastrointestinal (GI) tract and are critical for regulating motility. SMC contraction is regulated by changes in post-translational signaling and the st…

Myostatin deletion reverses myosteatosis and improves angiogenesis in obese mice Open

Andrew C. Speese, Caleb A. Padgett, Cody L. Rosewater, Zachary L. Corley, James Mintz , et al. · 2022

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): T32 Training Grant: Multi-Disciplinary Training Program in the Mechanisms of Cardiometabolic Disease Objective To test the hy…

Obesity Induces Disruption of Microvascular Endothelial Circadian Rhythm Open

Caleb A. Padgett, Joshua T. Butcher, Steven B. Haigh, Andrew C. Speese, Zachary L. Corley , et al. · 2022

Obese individuals are at significantly elevated risk of developing cardiovascular disease (CVD). Additionally, obesity has been associated with disrupted circadian rhythm, manifesting in abnormal sleeping and feeding patterns. To date, the…

Endothelin‐1 response to whole‐body vibration in obese and normal weight individuals Open

Adeola A. Sanni‐Ajibaye, Anson M. Blanks, Cassandra C. Derella, Abigayle B. Simon, Paula Rodriguez‐Miguelez , et al. · 2022

Upregulation of endothelin‐1 (ET‐1) is the hallmark of various cardiovascular diseases (CVD). The purpose of the present study was to assess the ET‐1 response to an acute bout of whole‐body vibration (WBV) in humans and to determine the ro…

Strong methane point sources contribute a disproportionate fraction of total emissions across multiple basins in the U.S. Open

Daniel Cusworth, Andrew K. Thorpe, Alana Ayasse, David W. Stepp, Joseph Heckler , et al. · 2022

Understanding, prioritizing, and mitigating methane (CH4) emissions requires quantifying methane budgets from facility scales to regional scales with the ability to differentiate between source sectors. We deployed a tiered observing syste…

Protein kinase N2 connects blood flow with NO production in a double AKT Open

David Fulton, David W. Stepp · 2021

Shear stress is an important regulator of blood flow, and luminal endothelial cells (ECs) sense increases in frictional forces and respond with an appropriate release of vasoactive mediators. In this issue of the JCI, Jin et al. identified…

Obesity and the Bidirectional Risk of Cancer and Cardiovascular Diseases in African Americans: Disparity vs. Ancestry Open

Avirup Guha, Xiaoling Wang, Ryan A. Harris, Anna‐Gay D. Nelson, David W. Stepp , et al. · 2021

Cardiovascular disease (CVD) and cancer often occur in the same individuals, in part due to the shared risk factors such as obesity. Obesity promotes adipose inflammation, which is pathogenically linked to both cardiovascular disease and c…

Nf1 heterozygous mice recapitulate the anthropometric and metabolic features of human neurofibromatosis type 1 Open

Rebekah Tritz, Tyler W. Benson, Valerie Harris, Farlyn Z. Hudson, James Mintz , et al. · 2020

Origins of Hypertension in Obesity Open

David Fulton, David W. Stepp · 2020

Whole body vibration elicits differential immune and metabolic responses in obese and normal weight individuals Open

Anson M. Blanks, Paula Rodriguez‐Miguelez, Jacob Looney, Matthew A. Tucker, Jinhee Jeong , et al. · 2019

Endothelial adenosine kinase deficiency ameliorates diet-induced insulin resistance Open

Jiean Xu, Qiuhua Yang, Xiaoyu Zhang, Zhiping Liu, Yapeng Cao , et al. · 2019

Insulin resistance-related disorders are associated with endothelial dysfunction. Accumulating evidence has suggested a role for adenosine signaling in the regulation of endothelial function. Here, we identified a crucial role of endotheli…

Enhancer of zeste homolog 2 (EZH2) regulates adipocyte lipid metabolism independent of adipogenic differentiation: Role of apolipoprotein E Open

Nicole K.H. Yiew, Charlotte Greenway, Abdalrahman Zarzour, Samah Ahmadieh, Brandee Goo , et al. · 2019

Enhancer of zeste homolog 2 (EZH2), an epigenetic regulator that plays a key role in cell differentiation and oncogenesis, was reported to promote adipogenic differentiation in vitro by catalyzing trimethylation of histone 3 lysine …

Galectin-3 is expressed in vascular smooth muscle cells and promotes pulmonary hypertension through changes in proliferation, apoptosis, and fibrosis Open

Scott A. Barman, Xueyi Li, Stephen Haigh, Dmitry Kondrikov, Keyvan Mahboubi , et al. · 2019

A defining characteristic of pulmonary hypertension (PH) is the extensive remodeling of pulmonary arteries (PAs), which results in progressive increases in vascular resistance and stiffness and eventual failure of the right ventricle. Ther…

Increased Muscle Mass Protects Against Hypertension and Renal Injury in Obesity Open

Joshua T. Butcher, James Mintz, Sebastian Larion, Shuiqing Qiu, Ling Ruan , et al. · 2018

Background Obesity compromises cardiometabolic function and is associated with hypertension and chronic kidney disease. Exercise ameliorates these conditions, even without weight loss. Although the mechanisms of exercise's benefits remain …

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