Pierre Hardy

Pierre Hardy
Université de Montréal | UdeM · Department of Pediatrics

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125
Publications
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Publications

Publications (125)
Article
The subretina, composed of the choroid and the retinal pigment epithelium (RPE), bears a critical role in proper vision. In addition to phagocytosis of photoreceptor debris, the RPE shuttles oxygen and nutrients to the neuroretina. For their own energy production, RPE cells mainly rely on lactate, a major by-product of glycolysis. Lactate, in turn,...
Article
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This study aims to investigate the role of microRNA let-7f in the dysfunction and degeneration of retinal pigment epithelium (RPE) cells through the induction of senescence and oxidative stress. Furthermore, we explore whether let-7f inhibition can protect these cells against sodium iodate (SI)-induced oxidative stress. Oxidative stress and let-7f...
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Lipid nanoparticles (LNPs) have established their position as nonviral vectors for gene therapy. Tremendous efforts have been made to modulate the properties of LNPs to unleash their full clinical potential. Among the strategies being pursued, the layer-by-layer (LbL) technique has gained considerable attention in the biomedical field. Illuminated...
Preprint
Full-text available
The sub-retina, composed of the choroid and the retinal pigment epithelium (RPE), bears a critical role in proper vision. In addition to phagocytosis of photoreceptor debris, the RPE shuttles oxygen and nutrients to the neuroretina. For their own energy production, RPE cells mainly rely on lactate, a major by-product of glycolysis. Lactate in turn...
Article
Uveal melanoma (UM) is the most common primary intraocular malignant tumor type in adults. Even after the treatment of the ocular tumor, the prognosis of patients with metastasis remains poor. Hence, an urgent unmet need exists to identify novel approaches to treat advanced UM. Previous studies have revealed G subunit alpha Q and alpha 11 (GNAQ/11)...
Preprint
The involvement of G-Protein-Coupled Receptors (GPCR) location bias in diverse cellular functions and their misregulation in pathology is an underexplored territory. HCAR1, a GPCR for lactate is linked to cancer progression, mainly due to Warburg effect, but its mechanism of action remains elusive. Here, we show HCAR1 has a nuclear localization, ca...
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Background HDAC9 (histone deacetylase 9) belongs to the class IIa family of histone deacetylases. This enzyme can shuttle freely between the nucleus and cytoplasm and promotes tissue-specific transcriptional regulation by interacting with histone and non-histone substrates. HDAC9 plays an essential role in diverse physiological processes including...
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Background Research suggests that hormone replacement therapy may increase the risk of breast cancer, and progestins such as norethisterone (NET) play a key role in this phenomenon. We have demonstrated that microRNA-181a (miR-181a) suppresses NET-promoted breast cancer cell survival. Nonetheless, the effects of NET and miR-181a on the tumorigenesi...
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Background and Aim Insufficient post-ischemic neovascularization is an initial key step in the pathogenesis of Oxygen-Induced Retinopathy (OIR). During neovascularization, pro-angiogenic cells (PACs) are mobilized from the bone marrow and integrate into ischemic tissues to promote angiogenesis. However, the modulation of PAC paracrine activity duri...
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Retinopathy of prematurity (ROP) is the primary cause of visual impairment and vision loss in premature infants, which results from the formation of aberrant retinal neovascularization (NV). An emerging body of evidence has shown that Müller cells are the predominant source of vascular endothelial growth factor (VEGF), which also serves as a chemoa...
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Uveal melanoma (UM) is the most common intraocular malignant tumor in adults with an extremely high mortality rate. Genetic and epigenetic dysregulation contribute to the development of UM. Recent discoveries have revealed dysregulation of the expression levels of microRNAs (miRNAs) as one of the epigenetic mechanisms underlying UM tumorigenesis. B...
Article
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy ). This article has been retracted at the request of the Edito...
Article
Survivin stands out as one of the most specific cancer targets discovered to date. Although single inhibition, e.g. through small interfering RNA (siRNA), has shown modest results in clinical trials, its combination with drugs holds promise to sensitize cancer cells to chemotherapeutics. In this study, we propose a sequential treatment of siRNA sur...
Article
Oxidative stress-induced retinal pigment epithelial cell (RPE) dysfunction is a primary contributing factor to early dry age-related macular degeneration (AMD). Oxidative injury to the retina may promote extracellular vesicles (EVs) released from RPE. In this study, we investigated the effects of oxidative-induced RPE cell-derived microparticles (R...
Article
The presence of elevated T lymphocytic microparticles (TLMPs) during respiratory illness is associated with airway and lung inflammation and epithelial injuries. Although inflammasome and IL-1β signaling are crucial in airway inflammation, little was known about their regulatory mechanism. We hypothesized that TLMPs trigger inflammasome activation...
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In subretinal inflammation, activated mononuclear phagocytes (MP) play a key role in the progression of retinopathies. Little is known about the mechanism involved in the loss of photoreceptors leading to vision impairment. Studying retinal damage induced by photo-oxidative stress, we observed that cluster of differentiation 36 (CD36)-deficient mic...
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Melphalan is an efficient chemotherapeutic agent that is currently used to treat retinoblastoma (Rb); however, the inherent risk of immunogenicity and the hazardous integration of this drug in healthy cells is inevitable. MicroRNAs are short non-coding single-stranded RNAs that affect a vast range of biological processes. Previously, we focused on...
Article
Background: Recent investigations have indicated that hormone therapy may increase the risk of breast cancer (BC), and the addition of synthetic progestins may play a critical role in this. Several studies have pointed out the important role of progesterone receptor membrane component 1 (PGRMC1) in the development of BC, especially with hormone th...
Article
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Aim: Excess angiogenesis or neovascularization plays a key role in the pathophysiology of several ocular diseases such as retinopathy of prematurity, diabetic retinopathy and exudative age-related macular degeneration. MicroRNA-181a (miR-181a) was found highly expressed in retina and choroidal tissues. This study intends to investigate the role of...
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Pathological choroidal neovascularization (CNV) is the common cause of vision loss in patients with age-related macular degeneration (AMD). Macrophages possess potential angiogenic function in CNV. We have demonstrated that human T lymphocyte-derived microparticles (LMPs) exert a potent antiangiogenic effect in several pathological neovascularizati...
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Age-related macular degeneration (AMD) is a leading cause of blindness worldwide affecting individuals over the age of 50. The neovascular form (NV AMD) is characterized by choroidal neovascularization (CNV) and responsible for the majority of central vision impairment. Using non-biased microRNA arrays and individual TaqMan qPCRs, we profiled miRNA...
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Retinoblastoma (Rb) is an aggressive childhood cancer of the developing retina. This disease is associated with epigenetic deregulation of several cancer pathways including upregulation of the proto-oncogene spleen tyrosine kinase (SYK). We have previously demonstrated that lymphocyte-derived microparticles (LMPs) possess strong cytotoxic effect on...
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Interest in the biological roles of cell membrane-derived vesicles in cell-cell communication has increased in recent years. Microparticles (MPs) are one such type of vesicles, ranging in diameter from 0.1 μm to 1 μm, and typically shed from the plasma membrane of eukaryotic cells undergoing activation or apoptosis. Here we describe the generation...
Article
Ischemic retinopathies are characterized by sequential vaso-obliteration followed by abnormal intravitreal neovascularization predisposing patients to retinal detachment and blindness. Ischemic retinopathies are associated with robust inflammation that leads to generation of IL-1 beta, which causes vascular degeneration and impairs retinal revascul...
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Neurons have an important role in retinal vascular development. Here we show that the G protein-coupled receptor (GPCR) coagulation factor II receptor-like 1 (F2rl1, previously known as Par2) is abundant in retinal ganglion cells and is associated with new blood vessel formation during retinal development and in ischemic retinopathy. After stimulat...
Article
Purpose Pathological choroidal neovascularization (CNV) is the major cause of severe vision loss in patients with age‐related macular degeneration (AMD). Inflammation is a key component in AMD, and macrophages play an important role in CNV generation. We have demonstrated that human T‐lymphocyte‐derived microparticles (LMPs) significantly inhibit a...
Article
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Unregulated cell proliferation or growth is a prominent characteristic of cancer. We have previously demonstrated that LMPs (cell membrane microparticles derived from apoptotic human CEM T lymphoma cells stimulated with actinomycin D) strongly suppress the proliferation of not only human endothelial cells but also mouse Lewis lung carcinoma cells....
Article
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The airway epithelium is critical for the normal integrity and function of the respiratory system. Excessive epithelial cell apoptosis contributes to cell damage and airway inflammation. We previously demonstrated that lymphocyte-derived microparticles (LMPs) induce apoptosis of human bronchial epithelial cells. However, the underlying mechanisms c...
Article
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Purpose: Choroidal neovascularization (CNV) is a major cause of vision loss in which choroidal vessels penetrate the RPE-an important source of growth factors, including nerve growth factor (NGF), whose activation via the p75NTR receptor promotes apoptosis and inhibits angiogenesis. We demonstrated previously that human T-lymphocyte-derived microp...
Article
Purpose Age‐related macular degeneration (AMD) represents the leading cause of vision loss in the elderly. The cumulative oxidative injury induces retinal pigment epithelium (RPE) membrane microparticles production, RPE cell death and cellular senescence. The RPE blebs are implicated in the formation of sub‐retinal deposit. Nonetheless, the pathoph...
Article
Objective: Proinflammatory cytokines contribute to the development of retinal vasculopathies. However, the role of these factors and the mechanisms by which they elicit their effects in retina are not known. We investigated whether activated microglia during early stages of ischemic retinopathy produces excessive interleukin-1β (IL-1β), which elic...
Article
Objective: Nitro-oxidative stress exerts a significant role in the genesis of hypoxic-ischemic (HI) brain injury. We previously reported that the ω-6 long chain fatty acids, transarachidonic acids (TAAs), which are nitrative stress-induced nonenzymatically generated arachidonic acid derivatives, trigger selective microvascular endothelial cell dea...
Article
Objective: The aim of this study was to determine if human CEM (human lymphoblastoma) T cell-derived microparticles (LMPs) could directly induce human bronchial epithelial cells (BECs) apoptosis and cytokine production. We also tested if LMPs phagocytosis by BECs played a role in mediating these effects. Methods: We generated LMPs from CEM (huma...
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Microparticles possess therapeutic potential regarding angiogenesis. We have demonstrated the contribution of apoptotic human CEM T lymphocyte-derived microparticles (LMPs) as inhibitors of angiogenic responses in animal models of inflammation and tumor growth. In the present study, we characterized the antivascular endothelial growth factor (VEGF)...
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Vascular degeneration and the ensuing abnormal vascular proliferation are central to proliferative retinopathies. Given the metabolic discordance associated with these diseases, the authors explored the role of ghrelin and its growth hormone secretagogue receptor 1a (GHSR-1a) in proliferative retinopathy. In a rat model of oxygen-induced retinopath...
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Retinopathy of prematurity (ROP) is a major cause of visual handicap in the pediatric population. To date, this disorder is thought to stem from deficient retinal vascularization. Intriguingly, functional electrophysiological studies in patients with mild or moderate ROP and in the oxygen-induced retinopathy (OIR) model in rats reveal central photo...
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Cellular migration is a complex process that requires the polymerization of actin filaments to drive cellular extension. Smooth muscle and cancer cell migration has been shown to be affected by coagulation factors, notably the factor VII (FVIIa) and tissue factor (TF) complex. The present studies delineated mediators involved with the process of FV...
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Age-related macular degeneration (AMD) represents the major cause of vision loss in industrialized nations. Laminar deposits in Bruch's membrane (BM) are among the first prominent histopathologic features, along with drusen formation, and have been found to contain oxidized lipids. Increases in concentrations of oxidized LDL (oxLDL) in plasma are o...
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Nonstop proliferation and vigorous neovascularization are two prominent characteristics of cancer. Antiangiogenic therapy has emerged as an important modality in treatment of solid tumors. Our previous work demonstrated that microparticles derived from apoptotic T-lymphocytes (LMPs) not only reduced the viabilities of high-proliferating cells, but...
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Retinopathy of prematurity (ROP) is a major complication of preterm birth. It encompasses a spectrum of pathologies that affect vision, from mild disease that resolves spontaneously to severe disease that causes retinal detachment and subsequent blindness. The pathologies are characterized by an arrest in normal retinal vascular development associa...
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Hypercapnia is regularly observed in chronic lung disease, such as bronchopulmonary dysplasia in preterm infants. Hypercapnia results in increased nitric oxide synthase activity and in vitro formation of nitrates. Neural vasculature of the immature subject is particularly sensitive to nitrative stress. We investigated whether exposure to clinically...
Article
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Ischemic retinopathies, such as retinopathy of prematurity and diabetic retinopathy are characterized by an initial microvascular degeneration, followed by an abnormal hypoxia-induced neovascularization. Oxygen-induced retinopathy (OIR) is a well-established in vivo model of ischemic retinopathies, which, although the triggering insult varies, all...
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Neovascular and degenerative diseases of the eye are leading causes of impaired vision and blindness in the world. Hypoxia or reduced oxygen tension is considered central to the pathogenesis of these disorders. Although the CD36 scavenger receptor features prominently in ocular homeostasis and pathology, little is known regarding its modulation by...
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Vasopressin type 2 receptor (V2R) exhibits mostly important properties for hydroosmotic equilibrium and, to a lesser extent, on vasomotricity. Drugs currently acting on this receptor are analogs of the natural neuropeptide, arginine vasopressin (AVP), and hence are competitive ligands. Peptides that reproduce specific sequences of a given receptor...
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Neovascularization (NV) of the normally avascular cornea arises from various causes including inflammation, infection, trauma, and contact lens wear. Corneal NV, whatever the cause, impairs vision and threatens the survival of corneal allografts, thus representing a serious clinical problem for which treatment is limited. Recent interest has focuse...
Article
Corneal avascularity is tightly regulated by a balance between angiogenic and antiangiogenic factors (angiogenic privilege). In the current study, we tested the hypothesis that the CD36+/+ antiangiogenic receptor contributes toward the maintenance of corneal avascularity. Corneas of CD36 wild-type (CD36) and knockout (CD36) mice aged 4, 16, 52, and...
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Vascularization is essential for tissue development and in restoration of tissue integrity after an ischemic injury. In studies of vascularization, the focus has largely been placed on vascular endothelial growth factor (VEGF), yet other factors may also orchestrate this process. Here we show that succinate accumulates in the hypoxic retina of rode...
Article
Inflammation participates in the genesis and progression of hypoxic-ischemic brain injury. Interleukin (IL)-1 is a major pro-inflammatory cytokine, which plays a dominant role in hypoxic-ischemic (and postinfectious) brain damage. Abundant evidence reveals the principal involvement of IL-1 over other pro-inflammatory cytokines. IL-1 interacts with...
Article
Although previous studies have demonstrated that hypoxia induces retinal ganglion cell (RGC) apoptosis and that transient retinal ischemia upregulates the expression of lysophosphatidic acid (LPA) receptors, it remains to be determined whether LPA(1) receptor mediates RGC degeneration during retinopathy of prematurity (ROP). By using an immortalize...
Article
The neonatal rat is born with its eyes closed and an immature visual system, that some say is equivalent to that of a human fetus at 26 weeks of gestation. From birth, the visual system of the newborn rat will gradually mature, the first manifestation of that being the opening of the eye which usually take place at postnatal day 14. Complete matura...
Article
Nitrative stress is an important regulator of vascular tone. We have recently described that trans-arachidonic acids (TAA) are major products of NO(2)(.)-mediated isomerization of arachidonic acid in cell membranes and that nitrative stress increases TAA levels leading to neural microvascular degeneration. In the present study, we explored whether...
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Full-text available
Recent studies have demonstrated that lymphocyte-derived microparticles (LMPs) impair endothelial cell function. However, no data currently exist regarding the contribution of LMPs in the regulation of angiogenesis. In the present study, we investigated the effects of LMPs on angiogenesis in vivo and in vitro and demonstrated that LMPs strongly sup...
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Oxidant stress plays a significant role in hypoxic-ischemic injury to the susceptible microvascular endothelial cells. During oxidant stress, lysophosphatidic acid (LPA) concentrations increase. We explored whether LPA caused cytotoxicity to neuromicrovascular cells and the potential mechanisms thereof. LPA caused a dose-dependent death of porcine...
Article
Neonates that survive very preterm birth have a high prevalence of cognitive impairment in later life. A common factor detected in premature infants is their postnatal exposure to high oxygen tension relative to that in utero. Hyperoxia is known to elicit injury to premature lung and retina. Because data on the exposure of the brain to hyperoxia ar...
Article
This study was undertaken to investigate the role of the antiangiogenic receptor CD36 during inflammatory corneal neovascularization (CNV). In a murine model of inflammatory CNV, CD36 expression was evaluated by RT-PCR and immunofluorescence. Mice subjected to CNV were treated topically (thrice daily) with CD36 functionally neutralizing antibodies...
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The renin-angiotensin system plays a key role in the initiation and maintenance of elevated blood pressure associated with altered intrauterine milieu. The current studies were undertaken to verify whether vascular response to ANG II is increased in adult offspring of low-protein fed dams (LP) compared with control (CTRL) and if so, to examine unde...
Article
Neovascularization after an ischemic insult is a beneficial attempt to salvage the injured tissue. Yet, despite the production of angiogenic factors within ischemic tissues, compensatory growth of new vessels fails to provide adequate vascularization. Thus, we hypothesized that local factors counter efficient revascularization. Whereas ischemia is...
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Thromboxane A(2) (TXA(2)) is an important lipid mediator generated during oxidative stress and implicated in ischemic neural injury. This autacoid was recently shown to partake in this injury process by directly inducing endothelial cytotoxicity. We explored the mechanisms for this TXA(2)-evoked neural microvascular endothelial cell death. Stable T...