Stephen L. Archer
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View article: Levosimendan Ameliorates Adverse Pulmonary Vascular Remodeling in Group-2 Pulmonary Hypertension
Levosimendan Ameliorates Adverse Pulmonary Vascular Remodeling in Group-2 Pulmonary Hypertension Open
Aims Pulmonary hypertension (PH) due to left heart disease (Group-2PH) is the most common form of PH and comprises two distinct subtypes: isolated post-capillary-PH (IpcPH) and combined post-and pre-capillary-PH (CpcPH). Despite its high p…
View article: Macrophage plasticity and glucose metabolism: the role of immunometabolism in pulmonary arterial hypertension
Macrophage plasticity and glucose metabolism: the role of immunometabolism in pulmonary arterial hypertension Open
Pulmonary arterial hypertension (PAH) is a syndrome characterized by a mean pulmonary artery pressure >20 mmHg and elevated pulmonary vascular resistance >2 Wood Units in the absence of left heart disease, chronic lung disease or hyp…
View article: Germline and somatic variants in <i>DNMT3A</i> and other clonal haematopoiesis of indeterminate potential genes contribute to pulmonary arterial hypertension
Germline and somatic variants in <i>DNMT3A</i> and other clonal haematopoiesis of indeterminate potential genes contribute to pulmonary arterial hypertension Open
Background and Aims Multiple germline gene variants promote familial and idiopathic pulmonary arterial hypertension (PAH); however, none are consistently identified in associated PAH with connective tissue disease (APAH-CTD). Moreover, the…
View article: Circular RNA Profiling Identifies <i>circ5078</i> as a <i>BMPR2</i> -Derived Regulator of Endothelial Proliferation and Stress Responses
Circular RNA Profiling Identifies <i>circ5078</i> as a <i>BMPR2</i> -Derived Regulator of Endothelial Proliferation and Stress Responses Open
BACKGROUND: The BMPR2 gene encodes the BMPR-II (bone morphogenetic protein receptor type-II) and is a known regulator of endothelial proliferation, apoptosis, and translational stress responses. While these effects are generally attributed…
View article: NDUFS2 (NADH:Ubiquinone oxidoreductase core subunit S2) in Mitochondrial Electron Transport Chain Complex I is Critical to Oxygen Responsiveness of Human Ductus Arteriosus Smooth Muscle Cells
NDUFS2 (NADH:Ubiquinone oxidoreductase core subunit S2) in Mitochondrial Electron Transport Chain Complex I is Critical to Oxygen Responsiveness of Human Ductus Arteriosus Smooth Muscle Cells Open
Rationale: Mitochondria in ductus arteriosus (DA) smooth muscle cells (DASMC) are oxygen sensors that trigger O2-induced vasoconstriction at birth; however, the molecular mechanisms of mitochondrial oxygen sensing are not fully understood.…
View article: Preclinical models of mitochondrial dysfunction: mtDNA and nuclear-encoded regulators in diverse pathologies
Preclinical models of mitochondrial dysfunction: mtDNA and nuclear-encoded regulators in diverse pathologies Open
Mitochondrial-driven diseases encompass a diverse group of single-gene and complex disorders, all linked to mitochondrial dysfunction, with significant impacts on human health. While there are rare mitochondrial diseases in which the prima…
View article: Inherited retinal disease pathway in the UK: a patient perspective and the potential of AI
Inherited retinal disease pathway in the UK: a patient perspective and the potential of AI Open
Background Inherited retinal diseases (IRDs) are the leading cause of blindness in young people in the UK. Despite significant improvements in genomics medicine, the diagnosis of these conditions remains challenging, and around 40% do not …
View article: Tet Methylcytosine Dioxygenase 2 (<scp><i>TET2</i></scp>) Mutation Drives a Global Hypermethylation Signature in Patients With Pulmonary Arterial Hypertension (<scp>PAH</scp>): Correlation With Altered Gene Expression Relevant to a Common T Cell Phenotype
Tet Methylcytosine Dioxygenase 2 (<span><i>TET2</i></span>) Mutation Drives a Global Hypermethylation Signature in Patients With Pulmonary Arterial Hypertension (<span>PAH</span>): Correlation With Altered Gene Expression Relevant to a Common T Cell Phenotype Open
Epigenetic changes in gene expression due to DNA methylation regulate pulmonary vascular structure and function. Genetic or acquired alterations in DNA methylation/demethylation can promote the development of pulmonary arterial hypertensio…
View article: Role of Dynamin 2 in mitochondrial fission and cell cycle regulation:<i>Dysregulation of a miR-124-3p-STAT3-DNM2-Drp1-RGCC pathway connects fission and cell proliferation in pulmonary arterial hypertension</i>
Role of Dynamin 2 in mitochondrial fission and cell cycle regulation:<i>Dysregulation of a miR-124-3p-STAT3-DNM2-Drp1-RGCC pathway connects fission and cell proliferation in pulmonary arterial hypertension</i> Open
Introduction Dynamin-related protein 1 (Drp1) activation increases mitochondrial fission and cell cycle progression in hyperproliferative cells, termed mitotic fission . However, the diameter of a fission apparatus comprised solely of Drp1…
View article: Neutrophil-mediated innate immune resistance to bacterial pneumonia is dependent on Tet2 function
Neutrophil-mediated innate immune resistance to bacterial pneumonia is dependent on Tet2 function Open
Individuals with clonal hematopoiesis of indeterminate potential (CHIP) are at increased risk of aging related health conditions and all-cause mortality, but whether CHIP affects risk of infection is much less clear. Using UK Biobank data,…
View article: Publisher Correction: Pulmonary hypertension
Publisher Correction: Pulmonary hypertension Open
View article: Germline and Somatic Mutations in DNA Methyltransferase 3A<i>(DNMT3A)</i>Predispose to Pulmonary Arterial Hypertension (PAH) in Humans and Mice:<i>Implications for Associated PAH</i>
Germline and Somatic Mutations in DNA Methyltransferase 3A<i>(DNMT3A)</i>Predispose to Pulmonary Arterial Hypertension (PAH) in Humans and Mice:<i>Implications for Associated PAH</i> Open
Background Mutations are found in 10-20% of idiopathic PAH (IPAH) patients, but none are consistently identified in connective tissue disease-associated PAH (APAH), which accounts for ∼45% of PAH cases. TET2 mutations, a cause of clonal he…
View article: Efficacy of Drpitor1a, a Dynamin-Related Protein 1 inhibitor, in Pulmonary Arterial Hypertension
Efficacy of Drpitor1a, a Dynamin-Related Protein 1 inhibitor, in Pulmonary Arterial Hypertension Open
Rationale Dynamin-related protein 1 (Drp1), a large GTPase, mediates mitochondrial fission. Increased Drp1-mediated fission permits accelerated mitosis, contributing to hyperproliferation of pulmonary artery smooth muscle cells (PASMC), wh…
View article: Dynamin‐related protein 1 is a critical regulator of mitochondrial calcium homeostasis during myocardial ischemia/reperfusion injury
Dynamin‐related protein 1 is a critical regulator of mitochondrial calcium homeostasis during myocardial ischemia/reperfusion injury Open
Dynamin‐related protein 1 (Drp1) is a cytosolic GTPase protein that when activated translocates to the mitochondria, meditating mitochondrial fission and increasing reactive oxygen species (ROS) in cardiomyocytes. Drp1 has shown promise as…
View article: The Herpes Simplex Virus pUL16 and pUL21 Proteins Prevent Capsids from Docking at Nuclear Pore Complexes
The Herpes Simplex Virus pUL16 and pUL21 Proteins Prevent Capsids from Docking at Nuclear Pore Complexes Open
After entry into cells, herpes simplex virus (HSV) nucleocapsids dock at nuclear pore complexes (NPCs) through which viral genomes are released into the nucleoplasm where viral gene expression, genome replication, and early steps in virion…
View article: The Role of Clonal Hematopoiesis of Indeterminant Potential and DNA (Cytosine-5)-Methyltransferase Dysregulation in Pulmonary Arterial Hypertension and Other Cardiovascular Diseases
The Role of Clonal Hematopoiesis of Indeterminant Potential and DNA (Cytosine-5)-Methyltransferase Dysregulation in Pulmonary Arterial Hypertension and Other Cardiovascular Diseases Open
DNA methylation is an epigenetic mechanism that regulates gene expression without altering gene sequences in health and disease. DNA methyltransferases (DNMTs) are enzymes responsible for DNA methylation, and their dysregulation is both a …
View article: Multi-omic and multispecies analysis of right ventricular dysfunction
Multi-omic and multispecies analysis of right ventricular dysfunction Open
View article: Humans with Pulmonary Arterial Hypertension display a global hypermethylation signature that worsens in patients who have a mutation in the gene encoding the methylation eraser, Tet Methylcytosine Dioxygenase 2 (TET2)
Humans with Pulmonary Arterial Hypertension display a global hypermethylation signature that worsens in patients who have a mutation in the gene encoding the methylation eraser, Tet Methylcytosine Dioxygenase 2 (TET2) Open
Epigenetic changes in gene expression due to DNA methylation are important physiologic and pathologic regulators of pulmonary vascular structure and function. Genetic or acquired alterations in DNA methylation or demethylation have been as…
View article: The Role of Mitochondrial Dynamics and Mitotic Fission in Regulating the Cell Cycle in Cancer and Pulmonary Arterial Hypertension: Implications for Dynamin-Related Protein 1 and Mitofusin2 in Hyperproliferative Diseases
The Role of Mitochondrial Dynamics and Mitotic Fission in Regulating the Cell Cycle in Cancer and Pulmonary Arterial Hypertension: Implications for Dynamin-Related Protein 1 and Mitofusin2 in Hyperproliferative Diseases Open
Mitochondria, which generate ATP through aerobic respiration, also have important noncanonical functions. Mitochondria are dynamic organelles, that engage in fission (division), fusion (joining) and translocation. They also regulate intrac…
View article: Defining the clinical validity of genes reported to cause pulmonary arterial hypertension
Defining the clinical validity of genes reported to cause pulmonary arterial hypertension Open
View article: Electron Leak From the Mitochondrial Electron Transport Chain Complex I at Site I <sub>Q</sub> Is Crucial for Oxygen Sensing in Rabbit and Human Ductus Arteriosus
Electron Leak From the Mitochondrial Electron Transport Chain Complex I at Site I <sub>Q</sub> Is Crucial for Oxygen Sensing in Rabbit and Human Ductus Arteriosus Open
Background As partial pressure of oxygen (pO 2 ) rises with the first breath, the ductus arteriosus (DA) constricts, diverting blood flow to the pulmonary circulation. The DA's O 2 sensor resides within smooth muscle cells. The DA smooth m…
View article: The Herpes Simplex Virus pUL16 and pUL21 Proteins Prevent Capsids from Docking at Nuclear Pore Complexes
The Herpes Simplex Virus pUL16 and pUL21 Proteins Prevent Capsids from Docking at Nuclear Pore Complexes Open
After entry into cells, herpes simplex virus (HSV) nucleocapsids dock at nuclear pore complexes (NPCs) through which viral genomes are released into the nucleoplasm where viral gene expression, genome replication, and early steps in virion…
View article: Asymptomatic surveillance testing for COVID-19 in health care professional students: lessons learned from a low prevalence setting
Asymptomatic surveillance testing for COVID-19 in health care professional students: lessons learned from a low prevalence setting Open
The novel coronavirus disease of 2019 (COVID-19) pandemic has severely impacted the training of health care professional students because of concerns of potential asymptomatic transmission to colleagues and vulnerable patients. From May 27…
View article: Effect of Chronic Digoxin Use on Mortality and Heart Failure Hospitalization in Pulmonary Arterial Hypertension
Effect of Chronic Digoxin Use on Mortality and Heart Failure Hospitalization in Pulmonary Arterial Hypertension Open
Background Digoxin acutely increases cardiac output in patients with pulmonary arterial hypertension (PAH) and right ventricular failure; however, the effects of chronic digoxin use in PAH are unclear. Methods and Results Data from the Min…
View article: Using omics to breathe new life into our understanding of the ductus arteriosus oxygen response
Using omics to breathe new life into our understanding of the ductus arteriosus oxygen response Open
The ductus arteriosus (DA) connects the aorta to the pulmonary artery (PA), directing placentally oxygenated blood away from the developing lungs. High pulmonary vascular resistance and low systemic vascular resistance facilitate shunting …
View article: Can artificial intelligence accelerate the diagnosis of inherited retinal diseases? Protocol for a data-only retrospective cohort study (Eye2Gene)
Can artificial intelligence accelerate the diagnosis of inherited retinal diseases? Protocol for a data-only retrospective cohort study (Eye2Gene) Open
Introduction Inherited retinal diseases (IRD) are a leading cause of visual impairment and blindness in the working age population. Mutations in over 300 genes have been found to be associated with IRDs and identifying the affected gene in…
View article: A Multi-omic and Multi-Species Analysis of Right Ventricular Failure
A Multi-omic and Multi-Species Analysis of Right Ventricular Failure Open
Right ventricular failure (RVF) is a leading cause of morbidity and mortality in multiple cardiovascular diseases, but there are no approved treatments for RVF as therapeutic targets are not clearly defined. Contemporary transcriptomic/pro…
View article: Acquired disorders of mitochondrial metabolism and dynamics in pulmonary arterial hypertension
Acquired disorders of mitochondrial metabolism and dynamics in pulmonary arterial hypertension Open
Pulmonary arterial hypertension (PAH) is an orphan disease of the cardiopulmonary unit that reflects an obstructive pulmonary vasculopathy and presents with hypertrophy, inflammation, fibrosis, and ultimately failure of the right ventricle…
View article: An integrated proteomic and transcriptomic signature of the failing right ventricle in monocrotaline induced pulmonary arterial hypertension in male rats
An integrated proteomic and transcriptomic signature of the failing right ventricle in monocrotaline induced pulmonary arterial hypertension in male rats Open
Aim: Pulmonary arterial hypertension (PAH) is an obstructive pulmonary vasculopathy that results in death from right ventricular failure (RVF). There is limited understanding of the molecular mechanisms of RVF in PAH. Methods: In a PAH-RVF…
View article: SARS-CoV-2 Mitochondriopathy in COVID-19 Pneumonia Exacerbates Hypoxemia
SARS-CoV-2 Mitochondriopathy in COVID-19 Pneumonia Exacerbates Hypoxemia Open