A5046070128- Cardiac Fibrosis and Remodeling
- Angiogenesis and VEGF in Cancer
- Cardiovascular Function and Risk Factors
- Receptor Mechanisms and Signaling
- Cardiac Imaging and Diagnostics
- Renin-Angiotensin System Studies
- Cancer, Lipids, and Metabolism
- Chemokine receptors and signaling
- Cancer, Stress, Anesthesia, and Immune Response
- Atherosclerosis and Cardiovascular Diseases
- Adipokines, Inflammation, and Metabolic Diseases
- Cardiac Ischemia and Reperfusion
- MicroRNA in disease regulation
- Lipoproteins and Cardiovascular Health
- Cancer, Hypoxia, and Metabolism
- Mesenchymal stem cell research
- ATP Synthase and ATPases Research
- Extracellular vesicles in disease
- Mast cells and histamine
- Cardiac Valve Diseases and Treatments
- Acute Myeloid Leukemia Research
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Mitochondrial Function and Pathology
- Nuclear Receptors and Signaling
- Proteoglycans and glycosaminoglycans research
Baker Heart and Diabetes Institute
2015-2021
Monash University
2021
The University of Melbourne
2021
CSL (Australia)
2020
Paris Cardiovascular Research Center
2010-2016
Inserm
2009-2016
Université Paris Cité
2010-2016
Délégation Paris 5
2012-2016
Sorbonne Paris Cité
2012-2016
Hôpital Européen Georges-Pompidou
2016
Acute myocardial infarction (MI) is a severe ischemic disease responsible for heart failure and sudden death. Inflammatory cells orchestrate postischemic cardiac remodeling after MI. Studies using mice with defective mast/stem cell growth factor receptor c-Kit have suggested key roles mast (MCs) in remodeling. Because mutations affect multiple types of both immune nonimmune origin, we addressed the impact MCs on function MI, c-Kit-independent MC-deficient (Cpa3(Cre/+)) mice. In response to...
Objective— Leukocyte infiltration in ischemic areas is a hallmark of myocardial infarction, and overwhelming innate immune cells has been shown to promote adverse remodeling cardiac rupture. Recruitment inflammatory the heart depends highly on family CC-chemokines their receptors. Here, we hypothesized that chemokine decoy receptor D6, which specifically binds scavenges CC-chemokines, might limit inflammation after infarction. Methods Results— D6 was expressed human murine infarcted...
Monocyte systemic levels are known to be a major determinant of ischaemic tissue revascularization, but the mechanisms mediating mobilization different monocyte subsets—Ly6Chi and Ly6Clo—to blood their respective role in post-ischaemic neovascularization not clearly understood. Here, we hypothesized that distinct chemokine/chemokine receptor pathways, namely CCL2/CCR2, CX3CL1/CX3CR1, CCL5/CCR5, differentially control subset levels, might thus impact vessel growth. In model murine hindlimb...
Interaction with heparan sulfate proteoglycans is supposed to provide chemokines the capacity immobilize on cell surface and extracellular matrix for accomplishing both tissue homing signaling of attracted cells. However, consequences exclusive invalidation such interaction roles played by endogenous in vivo remain unascertained.We engineered a mouse carrying Cxcl12 gene (Cxcl12(Gagtm)) mutation that precludes interactions structures while not affecting CXCR4-dependent CXCL12 isoforms (α, β,...
One dose of rHDL after myocardial ischemia increases both cardiac glucose uptake and heart function in healthy insulin-resistant mice.
Rationale: Decades of research have examined immune-modulatory strategies to protect the heart after an acute myocardial infarction and prevent progression failure but failed translate clinical benefit. Objective: To determine anti-inflammatory actions n-apo AI (Apo nanoparticles) that contribute cardiac tissue recovery infarction. Methods Results: Using a preclinical mouse model infarction, we demonstrate single intravenous bolus (CSL111, 80 mg/kg) delivered immediately reperfusion reduced...
C/EBP homologous protein-10 (CHOP-10) is a novel developmentally regulated nuclear protein that emerges as critical transcriptional integrator among pathways regulating differentiation, proliferation, and survival. In the present study, we analyzed role of CHOP-10 in postnatal neovascularization.Ischemia was induced by right femoral artery ligation wild-type CHOP-10(-/-) mice. capillary structure skeletal muscle, mRNA levels were upregulated ischemia diabetes mellitus. Angiographic score,...
Published clinical trials in patients with ischemic diseases show limited benefit of adult stem cell-based therapy, likely due to their restricted plasticity and commitment toward vascular cell lineage. We aim uncover the potent regenerative ability MesP1/stage-specific embryonic antigen 1 (SSEA-1)-expressing cardiovascular progenitors enriched from human cells (hESCs). Injection only 10(4) hESC-derived SSEA-1(+) /MesP1(+) cells, or progeny obtained after treatment VEGF-A PDGF-BB, was...
Objective— Catecholamines have been shown to control bone marrow (BM)–derived cell egress, yet the cellular and molecular mechanisms involved in this effect their subsequent participation postischemic vessel growth are poorly understood. Methods Results— Tyrosine hydroxylase mRNA levels, as well dopamine (DA) norepinephrine (NE) contents, were increased ischemic BM of mice with right femoral artery ligation. Angiographic score, capillary density, arteriole number markedly by treatments DA...
I n the setting of myocardial infarction (MI), mod- ulation excessive postischemic inflammatory response has therapeutic potential for cardiac tissue recovery and prevention subsequent progression to heart failure.This is supported by a large number anti-inflammatory approaches that demonstrate cardioprotective effects in preclinical models MI.However, translation these strategies achieve clinical benefit remains challenging, no treatment currently available improving outcomes following...
Aim: We have recently demonstrated that reconstituted high-density lipoprotein (rHDL) delivered immediately after myocardial infarction reduces infarct size and improves heart function in mice ( Heywood SE, Sci Transl Med, 2017 ). now examine potential immunomodulatory actions of HDL may underlie these effects. Methods: In male C57BL/6 mice, a single intravenous bolus rHDL (CSL-111, 80mg/kg human apoA-I, or saline) was at the time reperfusion following 30mins surgically-induced ischemia....
Aims: High-density lipoprotein (HDL) has multiple actions which may benefit post-ischemic heart function. We have shown in patients with type 2 diabetes that a single infusion of reconstituted HDL (rHDL, CSL-111) reduces inflammation1 including the number circulating monocytes, neutrophils and lymphocytes. Whether such effects contribute to improved function after ischemia reperfusion is unknown. This study aimed determine effect on inflammatory response insulin resistant mice. Methods...
Objectives: We have previously shown that apolipoprotein A-I nanoparticles (n-apoAI) delivered immediately after myocardial infarction reduces infarct size and improves heart function in mice. now examine anti-inflammatory actions of n-apoAI may underlie these effects. Methods: In male C57BL/6 mice, a single intravenous bolus n-apoA-I (CSL-111, 80mg/kg human apoA-I, or saline) was at the time reperfusion following 30mins surgically-induced ischemia. Effects on inflammatory response were...
Inflammatory cells orchestrate post-ischemic cardiac remodeling after myocardial infarction (MI). Studies in Kit mutant mice suggest key roles for mast tissue remodeling. However, mutations affect multiple cell types of both immune and non-immune origin. The aim this study was to address the impact on function following MI, using selectively cell-deficient (Cpa3Cre/+ mice). In response infarction, progenitors’ numbers (Lin-CD45+CD34+FcγRII/IIIhighβ7+) increased white adipose (day 3) heart 5)...
Inflammatory cells orchestrate post-ischemic cardiac remodeling after myocardial infarction (MI). Studies in Kit mutant mice suggest key roles for mast tissue remodeling. However, mutations affect multiple cell types of both immune and non-immune origin. The aim this study was to address the impact on function following MI, using selectively cell-deficient (Cpa3Cre/+ mice). number progenitor (Lin-CD45+CD34+FcγRII/III+β7+) increased bone marrow white adipose day 3 infiltrated heart 5...
Aims: High-density lipoprotein (HDL) is known to increase skeletal muscle glucose uptake, but whether this action extends the myocardium and has relevance in setting of ischemia unknown. This study aimed determine effect HDL on cardiac metabolism both vitro vivo, including during ischemia/reperfusion injury. Methods Results: treatment (50μg/mL) increased uptake (147±10%), glycolysis (154±11%) oxidation (130±6%) neonatal ventricular cardiomyocytes compared saline control. rapidly activated...