A5078080787- Pulmonary Hypertension Research and Treatments
- Circular RNAs in diseases
- RNA modifications and cancer
- MicroRNA in disease regulation
- Mitochondrial Function and Pathology
- Cardiovascular Function and Risk Factors
- Peptidase Inhibition and Analysis
- Cancer-related molecular mechanisms research
- PI3K/AKT/mTOR signaling in cancer
- Cancer Mechanisms and Therapy
- Renin-Angiotensin System Studies
- ATP Synthase and ATPases Research
- Cytokine Signaling Pathways and Interactions
- Cancer, Hypoxia, and Metabolism
- Cardiovascular Effects of Exercise
- Neonatal Respiratory Health Research
- Cardiac Fibrosis and Remodeling
- Metabolism and Genetic Disorders
- Macrophage Migration Inhibitory Factor
- Lung Cancer Treatments and Mutations
- Congenital Heart Disease Studies
- Protein Tyrosine Phosphatases
- Cardiac Valve Diseases and Treatments
- Adipose Tissue and Metabolism
- FOXO transcription factor regulation
AstraZeneca (Sweden)
2023-2025
Université Laval
2014-2023
Institut Universitaire de Cardiologie et de Pneumologie de Québec
2012-2022
Montreal Heart Institute
2016-2021
Canadian Heart Research Centre
2021
Clinical Research Management
2019
Society of Interventional Radiology
2019
Queen's University
2018
University of Ottawa
2018
Pulmonary Hypertension Association
2017
Pulmonary arterial hypertension (PAH) is characterized by enhanced proliferation and reduced apoptosis of pulmonary artery smooth muscle cells (PASMCs). Because microRNAs have been recently implicated in the regulation cell apoptosis, we hypothesized that these regulatory molecules might be etiology PAH. In this study, show miR-204 expression PASMCs down-regulated both human rodent down-regulation correlates with PAH severity accounts for proliferative antiapoptotic phenotypes PAH-PASMCs....
Pulmonary arterial hypertension (PAH) is associated with sustained inflammation known to promote DNA damage. Despite these unfavorable environmental conditions, PAH pulmonary smooth muscle cells (PASMCs) exhibit, in contrast healthy PASMCs, a pro-proliferative and anti-apoptotic phenotype, time by the activation of miR-204, nuclear factor activated T cells, hypoxia-inducible 1-α. We hypothesized that PAH-PASMCs have increased poly(ADP-ribose) polymerase-1 (PARP-1), critical enzyme implicated...
Right ventricular (RV) failure is the most important factor of both morbidity and mortality in pulmonary arterial hypertension (PAH). However, underlying mechanisms resulting failed RV PAH remain unknown. There growing evidence that angiogenesis microRNAs are involved PAH-associated failure. We hypothesized microRNA-126 (miR-126) downregulation decreases microvessel density promotes transition from a compensated to decompensated PAH.We studied free wall tissues humans with normal (n=17),...
Pulmonary arterial hypertension (PAH) remains a mysterious killer that, like cancer, is characterized by tremendous complexity. PAH development occurs under sustained and persistent environmental stress, such as inflammation, shear pseudo-hypoxia, more. After inducing an initial death of the endothelial cells, these stresses contribute with time to hyper-proliferative apoptotic resistant clone cells including pulmonary artery smooth muscle fibroblasts, even allowing vascular remodeling...
Pulmonary artery hypertension (PAH) is a proliferative disorder associated with enhanced pulmonary smooth muscle cell proliferation and suppressed apoptosis. The sustainability of this phenotype required the activation prosurvival transcription factor like signal transducers activators transcription-3 (STAT3) nuclear activated T (NFAT). Because these factors are implicated in several physiological processes, their inhibition PAH patients could be detrimental effects. Therefore, better...
Background— Evidence suggestive of endoplasmic reticulum (ER) stress in the pulmonary arteries patients with arterial hypertension has been described for decades but never therapeutically targeted. ER is a feature many conditions associated like hypoxia, inflammation, or loss-of-function mutations. signaling circulation involves activation activating transcription factor 6, which, via induction reticulin protein Nogo, can lead to disruption functional ER-mitochondria unit and increasingly...
Rationale: Pulmonary arterial hypertension (PAH) is a degenerative arteriopathy that leads to right ventricular (RV) failure. BRD4 (bromodomain-containing protein 4), member of the BET (bromodomain and extra-terminal motif) family, has been identified as critical epigenetic driver for cardiovascular diseases.Objectives: To explore therapeutic potential in PAH RVX208, clinically available inhibitor.Methods: Microvascular endothelial cells, smooth muscle cells isolated from distal pulmonary...
Mitochondrial signaling regulates both the acute and chronic response of pulmonary circulation to hypoxia, suppressed mitochondrial glucose oxidation contributes apoptosis-resistance proliferative diathesis in vascular remodeling hypertension. Hypoxia directly inhibits oxidation, whereas endoplasmic reticulum (ER)-stress can indirectly inhibit by decreasing calcium (Ca²⁺m levels). Both hypoxia ER stress promote remodeling. Uncoupling protein 2 (UCP2) has been shown conduct from mitochondria...
Right ventricular (RV) function is the major determinant for both functional capacity and survival in patients with pulmonary arterial hypertension (PAH). Despite recognized clinical importance of preserving RV function, subcellular mechanisms that govern transition from a compensated to decompensated state remain poorly understood as consequence there are no clinically established treatments failure paucity useful biomarkers. Accumulating evidence indicates long noncoding RNAs powerful...
Pulmonary arterial hypertension (PAH) is an obstructive vasculopathy characterized by enhanced pulmonary artery smooth muscle cell (PASMC) proliferation and suppressed apoptosis. This phenotype sustained the activation of Src/signal transducer activator transcription 3 (STAT3) axis, maintained a positive feedback loop involving miR-204 followed aberrant expression/activation its downstream targets such as Pim1 nuclear factor activated T-cells (NFATc2). Dehydroepiandrosterone (DHEA) steroid...
Pulmonary arterial hypertension (PAH) is a vascular remodeling disease characterized by enhanced proliferation of pulmonary artery smooth muscle cell (PASMC) and suppressed apoptosis. This phenotype has been associated with the upregulation oncoprotein survivin promoting mitochondrial membrane potential hyperpolarization (decreasing apoptosis) growth factor cytokines like PDGF, IL-6 vasoactive agent endothelin-1 (ET-1) PASMC proliferation. Krüppel-like 5 (KLF5), zinc-finger-type...
Right ventricular (RV) failure is a major cause of morbidity and mortality in pulmonary hypertension, but its mechanism remains unknown. Myocyte enhancer factor 2 (Mef2) has been implicated RV development, regulating metabolic, contractile, angiogenic genes. Moreover, Mef2 regulates microRNAs that have emerged as important determinants cardiac development disease, for which the role still unclear.We hypothesized critical Mef2-microRNAs axis failure.In rat hypertension model (monocrotaline),...
Rationale: Pulmonary arterial hypertension (PAH) is characterized by excessive proliferation of pulmonary artery smooth muscle cells (PASMCs). This sustained in time the down-regulation microRNA (miR)-204. In systemic vascular diseases, reduced miR-204 expression promotes biomineralization augmenting transcription factor Runt-related 2 (RUNX2). Implication RUNX2 PAH-related remodeling and presence calcified lesions PAH remain unexplored.Objectives: We hypothesized that up-regulated lungs...
Pulmonary arterial hypertension (PAH) is a vascular remodeling disease with poor prognosis and limited therapeutic options. Although the mechanisms contributing to in PAH are still unclear, several features, including hyperproliferation resistance apoptosis of pulmonary artery smooth muscle cells (PASMCs), have led emergence cancer-like concept. The molecular chaperone HSP90 (heat shock protein 90) directly associated malignant growth proliferation under stress conditions. In addition being...
Rationale: Pulmonary hypertension (PH) due to left heart disease (LHD), or group 2 PH, is the most prevalent form of PH worldwide. LHD often associated with metabolic syndrome (MetS). In 12% 13% cases, patients display vascular remodeling pulmonary arteries (PAs) poor prognosis. Unfortunately, underlying mechanisms remain unknown; PH-targeted therapies for this are nonexistent, and development a new preclinical model crucial. Among numerous pathways dysregulated in MetS, inflammation plays...
Background— The remodeled vessel wall in many vascular diseases such as restenosis after injury is characterized by proliferative and apoptosis-resistant smooth muscle cells. There evidence that proproliferative antiapoptotic states are a metabolic (glycolytic phenotype hyperpolarized mitochondria) electric (downregulation inhibition of plasmalemmal K + channels) remodeling involves activation the Akt pathway. Dehydroepiandrosterone (DHEA) naturally occurring clinically used steroid known to...
Background Pulmonary arterial hypertension ( PAH ) is a vasculopathy characterized by enhanced pulmonary artery smooth muscle cell PASMC proliferation and suppressed apoptosis. This results in both increase pressure vascular resistance. Recent studies have shown the implication of signal transducer activator transcription 3 STAT 3)/bone morphogenetic protein receptor 2 BMPR 2)/peroxisome proliferator‐activated gamma PPAR γ) . activation induces downregulation, decreasing γ, which contribute...
Pulmonary arterial hypertension (PAH) is a vascular remodeling disease with limited therapeutic options. Although exposed to stressful conditions, pulmonary artery (PA) smooth muscle cells (PASMCs) exhibit "cancer-like" pro-proliferative and anti-apoptotic phenotype. HDAC6 cytoplasmic histone deacetylase regulating multiple pro-survival mechanisms overexpressed in response stress cancer cells. Due the similarities between PAH, we hypothesized that expression increased PAH-PASMCs face...