Gaël Cagnone
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View article: Characterization of endothelin-converting enzyme 1 as a key enzyme in the multienzyme Aβ degradation pathway
Characterization of endothelin-converting enzyme 1 as a key enzyme in the multienzyme Aβ degradation pathway Open
Altered β-amyloid (Aβ) homeostasis is a critical event triggering the shift from healthy aging to Alzheimer disease (AD) through the overproduction and impaired clearance of Aβ peptides. The Aβ-degrading enzymes (ADEs) are a collective gro…
View article: Preterm Birth Conditions Alter Muscle Stem Cells and Their Niche, Causing Lasting Impairments in Muscle Regeneration and Function
Preterm Birth Conditions Alter Muscle Stem Cells and Their Niche, Causing Lasting Impairments in Muscle Regeneration and Function Open
Background Preterm birth‐related conditions affect the development of multiple organs, such as the heart, the lungs and the brain, leading to long‐term alterations in their function and a higher risk of comorbidities. Emerging evidence als…
View article: Targeting angiopoietin like-2 positive senescent cells improves cognitive impairment in adult male but not female atherosclerotic LDLr−/−;hApoB100+/+ mice
Targeting angiopoietin like-2 positive senescent cells improves cognitive impairment in adult male but not female atherosclerotic LDLr−/−;hApoB100+/+ mice Open
Cellular senescence contributes to cognitive decline in brain diseases. In dyslipidemic and atherosclerotic LDLr −/− ;hApoB100 +/+ (ATX) mice—a model exhibiting vascular dysfunctions and cognitive impairment—the role of senescence was inve…
View article: Loss of endothelial ALK1 signaling induces the emergence of a KIT+ angiogenic endothelial cluster driving brain arteriovenous malformations
Loss of endothelial ALK1 signaling induces the emergence of a KIT+ angiogenic endothelial cluster driving brain arteriovenous malformations Open
Background Hereditary Hemorrhagic Telangiectasia type 2 (HHT2) is a genetic disorder caused by mutations in the ALK1 ( ACVRL1 ) gene, encoding a receptor for Bone Morphogenetic Proteins 9 and 10 (BMP9/BMP10). HHT2 patients frequently devel…
View article: Folic Acid Supplementation Inhibits Proliferative Retinopathy of Prematurity
Folic Acid Supplementation Inhibits Proliferative Retinopathy of Prematurity Open
Background: Retinopathy of prematurity (ROP) is the major cause of blindness in children. It is a biphasic disease with retinal vessel growth cessation and loss (Phase I) followed by uncontrolled retinal vessel growth (Phase II). Folate is…
View article: Unconventional receptor functions and location-biased signaling of the lactate GPCR in the nucleus
Unconventional receptor functions and location-biased signaling of the lactate GPCR in the nucleus Open
G-protein-coupled receptors (GPCRs) are virtually involved in every physiological process. However, mechanisms for their ability to regulate a vast array of different processes remain elusive. An unconventional functional modality could at…
View article: Corticosteroids reduce pathological angiogenesis yet compromise reparative vascular remodeling in a model of retinopathy
Corticosteroids reduce pathological angiogenesis yet compromise reparative vascular remodeling in a model of retinopathy Open
Tissue inflammation is often broadly associated with cellular damage, yet sterile inflammation also plays critical roles in beneficial tissue remodeling. In the central nervous system, this is observed through a predominantly innate immune…
View article: Timed topical dexamethasone eye drops improve mitochondrial function to prevent severe retinopathy of prematurity
Timed topical dexamethasone eye drops improve mitochondrial function to prevent severe retinopathy of prematurity Open
Pathological neovascularization in retinopathy of prematurity (ROP) can cause visual impairment in preterm infants. Current ROP treatments which are not preventative and only address late neovascular ROP, are costly and can lead to severe …
View article: Senescence and Inflamm-Aging Are Associated With Endothelial Dysfunction in Men But Not Women With Atherosclerosis
Senescence and Inflamm-Aging Are Associated With Endothelial Dysfunction in Men But Not Women With Atherosclerosis Open
Coronary artery disease (CAD) is more prevalent in men than in women, with endothelial dysfunction, prodromal to CAD, developing a decade earlier in middle-aged men. We investigated the molecular basis of this dimorphism ex vivo in arteria…
View article: Timed topical dexamethasone eye drops improve mitochondrial function to prevent severe retinopathy of prematurity.
Timed topical dexamethasone eye drops improve mitochondrial function to prevent severe retinopathy of prematurity. Open
Pathological neovascularization in retinopathy of prematurity (ROP) can cause visual impairment in preterm infants. Current ROP treatments which are not preventative and only address late neovascular ROP, are costly and can lead to severe …
View article: Corticosteroids prevent pathological angiogenesis yet compromise reparative vascular remodeling in the retina
Corticosteroids prevent pathological angiogenesis yet compromise reparative vascular remodeling in the retina Open
Tissue inflammation is often broadly associated with cellular damage, yet sterile inflammation also plays critical roles in beneficial tissue remodeling. In the central nervous system (CNS), this is observed through a predominantly innate …
View article: Metabolic Reprogramming of the Neovascular Niche Promotes Regenerative Angiogenesis in Proliferative Retinopathy
Metabolic Reprogramming of the Neovascular Niche Promotes Regenerative Angiogenesis in Proliferative Retinopathy Open
Healthy blood vessels supply neurons to preserve metabolic function. In blinding proliferative retinopathies (PRs), pathological neovascular tufts often emerge in lieu of needed physiological revascularization of the ischemic neuroretina. …
View article: Metabolic Reprogramming of the Neovascular Niche Promotes Regenerative Angiogenesis in Proliferative Retinopathy
Metabolic Reprogramming of the Neovascular Niche Promotes Regenerative Angiogenesis in Proliferative Retinopathy Open
Healthy blood vessels supply neurons to preserve metabolic function. In blinding ischemic proliferative retinopathies (PRs), pathological neovascular tufts often emerge in lieu of needed physiological neuroretina revascularization. We show…
View article: Lack of HCAR1, the lactate GPCR, signaling promotes autistic-like behavior
Lack of HCAR1, the lactate GPCR, signaling promotes autistic-like behavior Open
The GPCR HCAR1 is known to be the sole receptor for lactate, which modulates its metabolic effects. Despite its significant role in many processes, mice deficient in HCAR1 exhibit no visible phenotype and are healthy and fertile. We perfor…
View article: A molecular atlas of brain neurovascular interactions reveals a spatiotemporal requirement of TGFβ signaling in brain angiogenesis
A molecular atlas of brain neurovascular interactions reveals a spatiotemporal requirement of TGFβ signaling in brain angiogenesis Open
Neurovascular interactions (NVIs) are critical in establishing vascular patterning, barrier function, and in regulating cerebral blood flow, thereby maintaining neuronal homeostasis and brain health. While developmental programs and neuron…
View article: Liver sinusoidal endothelial cells induce BMP6 expression in response to non–transferrin-bound iron
Liver sinusoidal endothelial cells induce BMP6 expression in response to non–transferrin-bound iron Open
Homeostatic adaptation to systemic iron overload involves transcriptional induction of bone morphogenetic protein 6 (BMP6) in liver sinusoidal endothelial cells (LSECs). BMP6 is then secreted to activate signaling of the iron hormone hepci…
View article: Nuclear Location Bias of HCAR1 Drives Cancer Malignancy through Numerous Routes
Nuclear Location Bias of HCAR1 Drives Cancer Malignancy through Numerous Routes Open
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…
View article: Triglyceride-derived fatty acids reduce autophagy in a model of retinal angiomatous proliferation
Triglyceride-derived fatty acids reduce autophagy in a model of retinal angiomatous proliferation Open
Dyslipidemia and autophagy have been implicated in the pathogenesis of blinding neovascular age-related macular degeneration (NV-AMD). VLDL receptor (VLDLR), expressed in photoreceptors with a high metabolic rate, facilitates the uptake of…
View article: Leveraging interacting signaling pathways to robustly improve the quality and yield of human pluripotent stem cell-derived hepatoblasts and hepatocytes
Leveraging interacting signaling pathways to robustly improve the quality and yield of human pluripotent stem cell-derived hepatoblasts and hepatocytes Open
Pluripotent stem cell (PSC)-derived hepatocyte-like cells (HLCs) have shown great potential as an alternative to primary human hepatocytes (PHHs) for in vitro modeling. Several differentiation protocols have been described to direct PSCs t…
View article: eNOS controls angiogenic sprouting and retinal neovascularization through the regulation of endothelial cell polarity
eNOS controls angiogenic sprouting and retinal neovascularization through the regulation of endothelial cell polarity Open
The roles of nitric oxide (NO) and endothelial NO synthase (eNOS) in the regulation of angiogenesis are well documented. However, the involvement of eNOS in the sprouting of endothelial tip-cells at the vascular front during sprouting angi…
View article: Cardiac Left Ventricle Mitochondrial Dysfunction After Neonatal Exposure to Hyperoxia: Relevance for Cardiomyopathy After Preterm Birth
Cardiac Left Ventricle Mitochondrial Dysfunction After Neonatal Exposure to Hyperoxia: Relevance for Cardiomyopathy After Preterm Birth Open
Background: Individuals born preterm present left ventricle changes and increased risk of cardiac diseases and heart failure. The pathophysiology of heart disease after preterm birth is incompletely understood. Mitochondria dysfunction is …
View article: Kinins and Their Receptors as Potential Therapeutic Targets in Retinal Pathologies
Kinins and Their Receptors as Potential Therapeutic Targets in Retinal Pathologies Open
The kallikrein-kinin system (KKS) contributes to retinal inflammation and neovascularization, notably in diabetic retinopathy (DR) and neovascular age-related macular degeneration (AMD). Bradykinin type 1 (B1R) and type 2 (B2R) receptors a…
View article: An allosteric interleukin-1 receptor modulator mitigates inflammation and photoreceptor toxicity in a model of retinal degeneration
An allosteric interleukin-1 receptor modulator mitigates inflammation and photoreceptor toxicity in a model of retinal degeneration Open
Background Inflammation and particularly interleukin-1β (IL-1β), a pro-inflammatory cytokine highly secreted by activated immune cells during early AMD pathological events, contribute significantly to retinal neurodegeneration. Here, we id…