Evangelos D. Michelakis
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View article: Cysteine oxidation of a redox hub within complex I can facilitate electron transport chain supercomplex formation
Cysteine oxidation of a redox hub within complex I can facilitate electron transport chain supercomplex formation Open
The mitochondrial electron transport chain (ETC) is a four complex unit that could be considered the most essential infrastructure within the mitochondria, as it primarily functions to generate the mitochondrial membrane potential (ΔΨm), w…
View article: Tumour initiated purinergic signalling promotes cardiomyocyte RBFOX1 degradation and cardiotoxicity from DNA damaging anticancer agents
Tumour initiated purinergic signalling promotes cardiomyocyte RBFOX1 degradation and cardiotoxicity from DNA damaging anticancer agents Open
It is well established tumour cells secrete signalling factors affecting distant normal tissues. What remains unresolved is whether these factors initiate a signalling cascade rendering terminally differentiated cardiomyocytes susceptible …
View article: Hyperacute response proteins synthesized on γ-tubulin-FTO-MARK4 translation microdomains regulate cancer’s acute stress response
Hyperacute response proteins synthesized on γ-tubulin-FTO-MARK4 translation microdomains regulate cancer’s acute stress response Open
Compared to normal cells, cancer cells are particularly resistant to stress, and their immediate response to stress is critical for subsequent adaptation, a major clinical challenge. With unbiased proteomics and transcriptomics, we identif…
View article: Abstract 2394 Oxidation of Cysteine Redox Switches Within Ndufs1 Can Promote Electron Transport Chain Supercomplex Assembly
Abstract 2394 Oxidation of Cysteine Redox Switches Within Ndufs1 Can Promote Electron Transport Chain Supercomplex Assembly Open
View article: Three-dimensional spatial localization and volume estimation of prostate tumors using 18F-PSMA-1007 PET/CT versus multiparametric MRI
Three-dimensional spatial localization and volume estimation of prostate tumors using 18F-PSMA-1007 PET/CT versus multiparametric MRI Open
View article: Cardioprotective effect of 19,20-epoxydocosapentaenoic acid (19,20-EDP) in ischaemic injury involves direct activation of mitochondrial sirtuin 3
Cardioprotective effect of 19,20-epoxydocosapentaenoic acid (19,20-EDP) in ischaemic injury involves direct activation of mitochondrial sirtuin 3 Open
Aims Although current clinical therapies following myocardial infarction (MI) have improved patient outcomes, morbidity, and mortality rates, secondary to ischaemic and ischaemia reperfusion (IR) injury remains high. Maintaining mitochondr…
View article: Fluorine-18 Prostate-Specific Membrane Antigen–1007 PET/CT vs Multiparametric MRI for Locoregional Staging of Prostate Cancer
Fluorine-18 Prostate-Specific Membrane Antigen–1007 PET/CT vs Multiparametric MRI for Locoregional Staging of Prostate Cancer Open
Importance Prostate-specific membrane antigen (PSMA) demonstrates overexpression in prostate cancer and correlates with tumor aggressiveness. PSMA positron emission tomography (PET) is superior to conventional imaging for the metastatic st…
View article: Pulmonary hypertension misdiagnosis due to preventable errors in echocardiography and right heart catheterization
Pulmonary hypertension misdiagnosis due to preventable errors in echocardiography and right heart catheterization Open
Objectives We hypothesized that preventable human errors in performance and reporting of transthoracic echocardiograms (TTEs) and right RHCs are common and may lead to misdiagnosis of pulmonary hypertension (PH) subgroups. Background PH is…
View article: Fasting increases susceptibility to acute myocardial ischaemia/reperfusion injury through a sirtuin-3 mediated increase in fatty acid oxidation
Fasting increases susceptibility to acute myocardial ischaemia/reperfusion injury through a sirtuin-3 mediated increase in fatty acid oxidation Open
Fasting increases susceptibility to acute myocardial ischaemia/reperfusion injury (IRI) but the mechanisms are unknown. Here, we investigate the role of the mitochondrial NAD + -dependent deacetylase, Sirtuin-3 (SIRT3), which has been show…
View article: Loss of the fructose transporter SLC2A5 inhibits cancer cell migration
Loss of the fructose transporter SLC2A5 inhibits cancer cell migration Open
Metastasis is the primary cause of cancer patient death and the elevation of SLC2A5 gene expression is often observed in metastatic cancer cells. Here we evaluated the importance of SLC2A5 in cancer cell motility by silencing its gene. We …
View article: Atrial Shunt Devices in Patients With Heart Failure and Preserved or Mildly Reduced Ejection Fraction and the Pulmonary Circulation: Promises and Concerns
Atrial Shunt Devices in Patients With Heart Failure and Preserved or Mildly Reduced Ejection Fraction and the Pulmonary Circulation: Promises and Concerns Open
View article: A reversible metabolic stress-sensitive regulation of CRMP2A orchestrates EMT/stemness and increases metastatic potential in cancer
A reversible metabolic stress-sensitive regulation of CRMP2A orchestrates EMT/stemness and increases metastatic potential in cancer Open
An epithelial-to-mesenchymal transition (EMT) phenotype with cancer stem cell-like properties is a critical feature of aggressive/metastatic tumors, but the mechanism(s) that promote it and its relation to metabolic stress remain unknown. …
View article: Heterogenous impairment of α cell function in type 2 diabetes is linked to cell maturation state
Heterogenous impairment of α cell function in type 2 diabetes is linked to cell maturation state Open
View article: Oral treprostinil improves pulmonary vascular compliance in pulmonary arterial hypertension
Oral treprostinil improves pulmonary vascular compliance in pulmonary arterial hypertension Open
Oral treprostinil has been shown to improve exercise capacity and delay disease progression in patients with pulmonary arterial hypertension (PAH), but its effects on hemodynamics are not well-characterized. The FREEDOM-EV trial was a Phas…
View article: SNPs for Genes Encoding the Mitochondrial Proteins Sirtuin3 and Uncoupling Protein 2 Are Associated With Disease Severity, Type 2 Diabetes, and Outcomes in Patients With Pulmonary Arterial Hypertension and This Is Recapitulated in a New Mouse Model Lacking Both Genes
SNPs for Genes Encoding the Mitochondrial Proteins Sirtuin3 and Uncoupling Protein 2 Are Associated With Disease Severity, Type 2 Diabetes, and Outcomes in Patients With Pulmonary Arterial Hypertension and This Is Recapitulated in a New Mouse Model Lacking Both Genes Open
Background Isolated loss‐of‐function single nucleotide polymorphisms (SNPs) for SIRT3 (a mitochondrial deacetylase) and UCP2 (an atypical uncoupling protein enabling mitochondrial calcium entry) have been associated with both pulmonary art…
View article: Early Start of Oral Clarithromycin Is Associated with Better Outcome in COVID-19 of Moderate Severity: The ACHIEVE Open-Label Single-Arm Trial
Early Start of Oral Clarithromycin Is Associated with Better Outcome in COVID-19 of Moderate Severity: The ACHIEVE Open-Label Single-Arm Trial Open
ClinicalTrials.gov, NCT04398004.
View article: A Phase-2 NIH-sponsored Randomized Clinical Trial of Rituximab in Scleroderma-associated Pulmonary Arterial Hypertension Did Not Reach Significance for Its Endpoints: End of Story? Not So Fast!
A Phase-2 NIH-sponsored Randomized Clinical Trial of Rituximab in Scleroderma-associated Pulmonary Arterial Hypertension Did Not Reach Significance for Its Endpoints: End of Story? Not So Fast! Open
View article: Mechanical Stiffness Controls Dendritic Cell Metabolism and Function
Mechanical Stiffness Controls Dendritic Cell Metabolism and Function Open
Stiffness in the tissue microenvironment changes in most diseases and immunological conditions, but its direct influence on the immune system is poorly understood. Here, we show that static tension impacts immune cell function, maturation,…
View article: Beneficial Effects of Intermediate Dosage of Anticoagulation Treatment on the Prognosis of Hospitalized COVID-19 Patients: The ETHRA Study
Beneficial Effects of Intermediate Dosage of Anticoagulation Treatment on the Prognosis of Hospitalized COVID-19 Patients: The ETHRA Study Open
Anticoagulation treatment (particularly intermediate dosage) appears to have positive impact on COVID-19 inpatients' prognosis by inhibiting both coagulation and inflammatory cascades.
View article: Early start of oral clarithromycin is associated with better outcome in COVID-19 of moderate severity: the ACHIEVE open-label trial
Early start of oral clarithromycin is associated with better outcome in COVID-19 of moderate severity: the ACHIEVE open-label trial Open
Background To study the efficacy of oral clarithromycin in moderate COVID-19. Methods An open-label non-randomized trial in 90 patients with COVID-19 of moderate severity was conducted between May and October 2020. The primary endpoint was…
View article: p53‐Mediated Repression of the PGC1A (PPARG Coactivator 1α) and APLNR (Apelin Receptor) Signaling Pathways Limits Fatty Acid Oxidation Energetics: Implications for Cardio‐oncology
p53‐Mediated Repression of the PGC1A (PPARG Coactivator 1α) and APLNR (Apelin Receptor) Signaling Pathways Limits Fatty Acid Oxidation Energetics: Implications for Cardio‐oncology Open
View article: Combination Therapy with Oral Treprostinil for Pulmonary Arterial Hypertension. A Double-Blind Placebo-controlled Clinical Trial
Combination Therapy with Oral Treprostinil for Pulmonary Arterial Hypertension. A Double-Blind Placebo-controlled Clinical Trial Open
Rationale: Oral treprostinil improves exercise capacity in patients with pulmonary arterial hypertension (PAH), but the effect on clinical outcomes was unknown.Objectives: To evaluate the effect of oral treprostinil compared …
View article: The time has come to pull renal cancer’s sweet tooth
The time has come to pull renal cancer’s sweet tooth Open
The metabolic theory of cancer is based on cancer’s unique suppression of mitochondrial glucose oxidation and upregulation of cytosolic glycolysis, first identified by Otto Warburg nearly 100 years ago (1). This “Warburg effect” has been s…
View article: The time has come to pull renal cancer’s sweet tooth
The time has come to pull renal cancer’s sweet tooth Open
View article: Quantification of lung water in heart failure using cardiovascular magnetic resonance imaging
Quantification of lung water in heart failure using cardiovascular magnetic resonance imaging Open
View article: Assessment of Right Ventricular Function in the Research Setting: Knowledge Gaps and Pathways Forward. An Official American Thoracic Society Research Statement
Assessment of Right Ventricular Function in the Research Setting: Knowledge Gaps and Pathways Forward. An Official American Thoracic Society Research Statement Open
This statement provides a roadmap to further advance the state of knowledge, with the ultimate goal of developing RV-targeted therapies for patients with RV failure of any etiology.
View article: Immunity Comes to Play in the “Sex Paradox” of Pulmonary Arterial Hypertension
Immunity Comes to Play in the “Sex Paradox” of Pulmonary Arterial Hypertension Open
View article: Mitochondrial HSP90 Accumulation Promotes Vascular Remodeling in Pulmonary Arterial Hypertension
Mitochondrial HSP90 Accumulation Promotes Vascular Remodeling in Pulmonary Arterial Hypertension Open
Our data show for the first time that accumulation of mtHSP90 is a feature of PAH-PASMCs and a key regulator of mitochondrial homeostasis contributing to vascular remodeling in PAH.
View article: Oxygen Sensing in the Pulmonary Circulation
Oxygen Sensing in the Pulmonary Circulation Open
View article: An Official American Thoracic Society Workshop Report: Obesity and Metabolism. An Emerging Frontier in Lung Health and Disease
An Official American Thoracic Society Workshop Report: Obesity and Metabolism. An Emerging Frontier in Lung Health and Disease Open
The world is in the midst of an unprecedented epidemic of obesity. This epidemic has changed the presentation and etiology of common diseases. For example, steatohepatitis, directly attributable to obesity, is now the most common cause of …