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Article: Assessment of vascular regeneration in the cns using the mouse retina

Miloudi, Khalil / Dejda, Agnieszka / Binet, François / Lapalme, Eric / Cerani, Agustin / Sapieha, Przemyslaw

Journal of visualized experiments. 2014 June 23, , no. 88

2014

Abstract: The rodent retina is perhaps the most accessible mammalian system in which to investigate neurovascular interplay within the central nervous system (CNS). It is increasingly being recognized that several neurodegenerative diseases such as Alzheimer’s, ... ...

Abstract	The rodent retina is perhaps the most accessible mammalian system in which to investigate neurovascular interplay within the central nervous system (CNS). It is increasingly being recognized that several neurodegenerative diseases such as Alzheimer’s, multiple sclerosis, and amyotrophic lateral sclerosis present elements of vascular compromise. In addition, the most prominent causes of blindness in pediatric and working age populations (retinopathy of prematurity and diabetic retinopathy, respectively) are characterized by vascular degeneration and failure of physiological vascular regrowth. The aim of this technical paper is to provide a detailed protocol to study CNS vascular regeneration in the retina. The method can be employed to elucidate molecular mechanisms that lead to failure of vascular growth after ischemic injury. In addition, potential therapeutic modalities to accelerate and restore healthy vascular plexuses can be explored. Findings obtained using the described approach may provide therapeutic avenues for ischemic retinopathies such as that of diabetes or prematurity and possibly benefit other vascular disorders of the CNS.
Keywords	amyotrophic lateral sclerosis ; blindness ; central nervous system ; diabetic retinopathy ; mice ; premature birth ; regrowth ; retina ; sclerosis ; therapeutics
Language	English
Dates of publication	2014-0623
Size	p. e51351.
Publishing place	Journal of Visualized Experiments
Document type	Article
ZDB-ID	2259946-0
ISSN	1940-087X
ISSN	1940-087X
DOI	10.3791/51351
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: miR-106b suppresses pathological retinal angiogenesis.

Ménard, Catherine / Wilson, Ariel M / Dejda, Agnieszka / Miloudi, Khalil / Binet, François / Crespo-Garcia, Sergio / Parinot, Célia / Pilon, Frédérique / Juneau, Rachel / Andriessen, Elisabeth Mma / Mawambo, Gaëlle / SanGiovanni, John Paul / De Guire, Vincent / Sapieha, Przemyslaw

Aging

2020 Volume 12, Issue 24, Page(s) 24836–24852

Abstract: MicroRNAs are small non-coding RNAs that post-transcriptionally regulate gene expression. We recently demonstrated that levels of miR-106b were significantly decreased in the vitreous and plasma of patients with neovascular age-related macular ... ...

Abstract	MicroRNAs are small non-coding RNAs that post-transcriptionally regulate gene expression. We recently demonstrated that levels of miR-106b were significantly decreased in the vitreous and plasma of patients with neovascular age-related macular degeneration (AMD). Here we show that expression of the miR-106b-25 cluster is negatively regulated by the unfolded protein response pathway of protein kinase RNA-like ER kinase (PERK) in a mouse model of neovascular AMD. A reduction in levels of miR-106b triggers vascular growth both
MeSH term(s)	Animals ; Cell Line ; Cell Movement/genetics ; Choroidal Neovascularization/genetics ; Choroidal Neovascularization/pathology ; Diabetic Retinopathy ; Disease Models, Animal ; Endoplasmic Reticulum Stress/genetics ; Endothelial Cells ; Eye Burns ; Humans ; Laser Therapy ; Macular Degeneration/genetics ; Macular Degeneration/pathology ; Mice ; MicroRNAs/genetics ; Oxygen/toxicity ; Retinal Neovascularization/genetics ; Retinal Neovascularization/pathology ; Retinopathy of Prematurity ; Unfolded Protein Response/genetics ; eIF-2 Kinase/genetics ; eIF-2 Kinase/metabolism
Chemical Substances	MIRN106 microRNA, human ; MicroRNAs ; Mirn106 microRNA, mouse ; PERK kinase (EC 2.7.11.1) ; eIF-2 Kinase (EC 2.7.11.1) ; Oxygen (S88TT14065)
Language	English
Publishing date	2020-12-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1945-4589
ISSN (online)	1945-4589
DOI	10.18632/aging.202404
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Article ; Online: Assessment of vascular regeneration in the CNS using the mouse retina.

Miloudi, Khalil / Dejda, Agnieszka / Binet, François / Lapalme, Eric / Cerani, Agustin / Sapieha, Przemyslaw

Journal of visualized experiments : JoVE

2014 , Issue 88, Page(s) e51351

Abstract	The rodent retina is perhaps the most accessible mammalian system in which to investigate neurovascular interplay within the central nervous system (CNS). It is increasingly being recognized that several neurodegenerative diseases such as Alzheimer's, multiple sclerosis, and amyotrophic lateral sclerosis present elements of vascular compromise. In addition, the most prominent causes of blindness in pediatric and working age populations (retinopathy of prematurity and diabetic retinopathy, respectively) are characterized by vascular degeneration and failure of physiological vascular regrowth. The aim of this technical paper is to provide a detailed protocol to study CNS vascular regeneration in the retina. The method can be employed to elucidate molecular mechanisms that lead to failure of vascular growth after ischemic injury. In addition, potential therapeutic modalities to accelerate and restore healthy vascular plexuses can be explored. Findings obtained using the described approach may provide therapeutic avenues for ischemic retinopathies such as that of diabetes or prematurity and possibly benefit other vascular disorders of the CNS.
MeSH term(s)	Animals ; Brain Ischemia/physiopathology ; Disease Models, Animal ; Mice ; Neovascularization, Pathologic/physiopathology ; Nerve Regeneration/physiology ; Oxygen ; Retina/drug effects ; Retina/pathology ; Retina/physiopathology ; Retinal Diseases/physiopathology ; Retinal Vessels/pathology
Chemical Substances	Oxygen (S88TT14065)
Language	English
Publishing date	2014-06-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Video-Audio Media
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/51351
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Article ; Online: Gut microbiota influences pathological angiogenesis in obesity-driven choroidal neovascularization.

Andriessen, Elisabeth Mma / Wilson, Ariel M / Mawambo, Gaelle / Dejda, Agnieszka / Miloudi, Khalil / Sennlaub, Florian / Sapieha, Przemyslaw

EMBO molecular medicine

2016 Volume 8, Issue 12, Page(s) 1366–1379

Abstract: Age-related macular degeneration in its neovascular form (NV AMD) is the leading cause of vision loss among adults above the age of 60. Epidemiological data suggest that in men, overall abdominal obesity is the second most important environmental risk ... ...

Abstract	Age-related macular degeneration in its neovascular form (NV AMD) is the leading cause of vision loss among adults above the age of 60. Epidemiological data suggest that in men, overall abdominal obesity is the second most important environmental risk factor after smoking for progression to late-stage NV AMD To date, the mechanisms that underscore this observation remain ill-defined. Given the impact of high-fat diets on gut microbiota, we investigated whether commensal microbes influence the evolution of AMD Using mouse models of NV AMD, microbiotal transplants, and other paradigms that modify the gut microbiome, we uncoupled weight gain from confounding factors and demonstrate that high-fat diets exacerbate choroidal neovascularization (CNV) by altering gut microbiota. Gut dysbiosis leads to heightened intestinal permeability and chronic low-grade inflammation characteristic of inflammaging with elevated production of IL-6, IL-1β, TNF-α, and VEGF-A that ultimately aggravate pathological angiogenesis.
MeSH term(s)	Animals ; Choroidal Neovascularization/pathology ; Cytokines/blood ; Diet, High-Fat/adverse effects ; Disease Models, Animal ; Dysbiosis/etiology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Gastrointestinal Tract/microbiology ; Inflammation/pathology ; Macular Degeneration/epidemiology ; Macular Degeneration/pathology ; Mice ; Neovascularization, Pathologic ; Obesity/complications ; Obesity/pathology
Chemical Substances	Cytokines
Language	English
Publishing date	2016-12-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2467145-9
ISSN	1757-4684 ; 1757-4676
ISSN (online)	1757-4684
ISSN	1757-4676
DOI	10.15252/emmm.201606531
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Article: The mode of administration of total parenteral nutrition and nature of lipid content influence the generation of peroxides and aldehydes

Miloudi, Khalil / Comte, Blandine / Rouleau, Thérèse / Montoudis, Alain / Levy, Emile / Lavoie, Jean-Claude

Clinical nutrition. 2012 Aug., v. 31, no. 4

2012

Abstract: BACKGROUND & AIMS: The absence of light protection of neonatal total parenteral nutrition (PN) contributes to the generation of 4-hydroxynonenal and peroxides. 4-Hydroxynonenal is suspected to be involved in PN-related liver complications. Aims: To find ... ...

Abstract	BACKGROUND & AIMS: The absence of light protection of neonatal total parenteral nutrition (PN) contributes to the generation of 4-hydroxynonenal and peroxides. 4-Hydroxynonenal is suspected to be involved in PN-related liver complications. Aims: To find a practical modality to reduce 4-hydroxynonenal in PN and assess in vivo the impact of PN containing low 4-hydroxynonenal concentration. METHODS: Six modalities of delivering PN were compared for the in vitro generation of peroxides and 4-hydroxynonenal: 1) MV-AA−L: light-protected (-L) solution containing multivitamin (MV) mixed with amino acids + dextrose (AA); 2) MV-AA+L: MV-AA without photo-protection (+L); 3) MV-LIP+L: MV mixed with lipid emulsion (LIP). LIP was a) Intralipid20%® or b) Omegaven®. Hepatic markers of oxidative stress (glutathione, F2α-isoprostanes, GS-HNE) and inflammation (mRNA of TNF-α and IL-1) were measured in newborn guinea pigs infused during 4-days with MV-AA+L compounded with Intralipid20%® or Omegaven®. RESULTS: Hydroperoxides and 4-hydroxynonenal were the lowest in MV-AA−L and the highest in MV-LIP+L. MV-AA+L with Omegaven® was associated with the lowest levels of markers of oxidative stress and inflammation. CONCLUSION: Compared to Intralipid20%®, Omegaven® reduces oxidative stress associated with PN and prevents liver inflammation. These findings offer an alternative strategy to light protection of PN, which in the clinical setting is a cumbersome modality.
Keywords	aldehydes ; amino acids ; emulsions ; glucose ; glutathione ; guinea pigs ; hydroperoxides ; inflammation ; lipid content ; lipids ; liver ; messenger RNA ; neonates ; oxidative stress ; total parenteral nutrition
Language	English
Dates of publication	2012-08
Size	p. 526-534.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	604812-2
ISSN	1532-1983 ; 0261-5614
ISSN (online)	1532-1983
ISSN	0261-5614
DOI	10.1016/j.clnu.2011.12.012
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Gut microbiota influences pathological angiogenesis in obesity‐driven choroidal neovascularization

Elisabeth MMA Andriessen / Ariel M Wilson / Gaelle Mawambo / Agnieszka Dejda / Khalil Miloudi / Florian Sennlaub / Przemyslaw Sapieha

EMBO Molecular Medicine, Vol 8, Iss 12, Pp 1366-

2016 Volume 1379

Abstract: Abstract Age‐related macular degeneration in its neovascular form (NV AMD) is the leading cause of vision loss among adults above the age of 60. Epidemiological data suggest that in men, overall abdominal obesity is the second most important ... ...

Abstract	Abstract Age‐related macular degeneration in its neovascular form (NV AMD) is the leading cause of vision loss among adults above the age of 60. Epidemiological data suggest that in men, overall abdominal obesity is the second most important environmental risk factor after smoking for progression to late‐stage NV AMD. To date, the mechanisms that underscore this observation remain ill‐defined. Given the impact of high‐fat diets on gut microbiota, we investigated whether commensal microbes influence the evolution of AMD. Using mouse models of NV AMD, microbiotal transplants, and other paradigms that modify the gut microbiome, we uncoupled weight gain from confounding factors and demonstrate that high‐fat diets exacerbate choroidal neovascularization (CNV) by altering gut microbiota. Gut dysbiosis leads to heightened intestinal permeability and chronic low‐grade inflammation characteristic of inflammaging with elevated production of IL‐6, IL‐1β, TNF‐α, and VEGF‐A that ultimately aggravate pathological angiogenesis.
Keywords	age‐related macular degeneration ; angiogenesis ; gut microbiota ; inflammaging ; obesity ; Medicine (General) ; R5-920 ; Genetics ; QH426-470
Language	English
Publishing date	2016-12-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
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Article ; Online: Hexapeptides from human milk prevent the induction of oxidative stress from parenteral nutrition in the newborn guinea pig.

Miloudi, Khalil / Tsopmo, Apollinaire / Friel, James K / Rouleau, Thérèse / Comte, Blandine / Lavoie, Jean-Claude

Pediatric research

2012 Volume 71, Issue 6, Page(s) 675–681

Abstract: Introduction: In preterm neonates, peroxides contaminating total parenteral nutrition (TPN) contribute to oxidative stress, which is suspected to be a strong inducer of hepatic complications related to prematurity. Recently, others reported that ... ...

Abstract	Introduction: In preterm neonates, peroxides contaminating total parenteral nutrition (TPN) contribute to oxidative stress, which is suspected to be a strong inducer of hepatic complications related to prematurity. Recently, others reported that hexapeptides derived from human milk (HM) exerted free radical-scavenging activities in vitro. Therefore, the aim of this study was to assess the capacity of these hexapeptides to limit the generation of peroxides in TPN and to prevent TPN-induced hepatic oxidative stress. Methods: At 3 d of life, guinea pigs were infused, through a catheter in jugular vein, with TPN containing or not peptide-A (YGYTGA) or peptide-B (ISELGW). Peroxide concentrations were measured in TPN solutions, whereas glutathione, glutathionyl-1,4-dihydroxynonenal (GS-HNE) and mRNA levels of interleukin-1 (IL-1) and tumor necrosis factor-α (TNFα) were determined in liver after 4 d of infusion. Results: The addition of peptide-A to TPN allowed a reduction in peroxide contamination by half. In vivo, peptide-A or peptide-B corrected the hepatic oxidative status induced by TPN. Indeed, both peptides lowered the hepatic redox potential of glutathione and the level of GS-HNE, a marker of lipid peroxidation. As compared with animals infused with TPN without peptide, the hepatic mRNA levels of IL-1 and TNFα were lower in animals infused with TPN containing peptide-A or peptide-B. Discussion: These results suggest that the addition of YGYTGA or ISELGW to TPN will reduce oxidative stress in newborns. The reduction in mRNA of two proinflammatory cytokines could be important for the incidence of hepatic complications related to TPN.
MeSH term(s)	Animals ; Animals, Newborn/physiology ; Enkephalins/pharmacology ; Free Radical Scavengers/metabolism ; Glutathione/metabolism ; Guinea Pigs ; Humans ; Interleukin-1/metabolism ; Liver/metabolism ; Male ; Milk, Human ; Models, Animal ; Oncogene Protein pp60(v-src)/pharmacology ; Oxidative Stress/drug effects ; Oxidative Stress/physiology ; Parenteral Nutrition/adverse effects ; Peptide Fragments/pharmacology ; Peroxides/metabolism ; Protein Precursors/pharmacology ; Tumor Necrosis Factor-alpha/metabolism
Chemical Substances	Enkephalins ; Free Radical Scavengers ; Interleukin-1 ; Peptide Fragments ; Peroxides ; Protein Precursors ; Tumor Necrosis Factor-alpha ; peptide A ; peptide B ; Oncogene Protein pp60(v-src) (EC 2.7.10.2) ; Glutathione (GAN16C9B8O)
Language	English
Publishing date	2012-02-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	4411-8
ISSN	1530-0447 ; 0031-3998
ISSN (online)	1530-0447
ISSN	0031-3998
DOI	10.1038/pr.2012.29
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Zs.A 564: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 373: Show issues

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Article ; Online: The mode of administration of total parenteral nutrition and nature of lipid content influence the generation of peroxides and aldehydes.

Miloudi, Khalil / Comte, Blandine / Rouleau, Thérèse / Montoudis, Alain / Levy, Emile / Lavoie, Jean-Claude

Clinical nutrition (Edinburgh, Scotland)

2012 Volume 31, Issue 4, Page(s) 526–534

Abstract: Background & aims: The absence of light protection of neonatal total parenteral nutrition (PN) contributes to the generation of 4-hydroxynonenal and peroxides. 4-Hydroxynonenal is suspected to be involved in PN-related liver complications.: Aims: To ... ...

Abstract	Background & aims: The absence of light protection of neonatal total parenteral nutrition (PN) contributes to the generation of 4-hydroxynonenal and peroxides. 4-Hydroxynonenal is suspected to be involved in PN-related liver complications. Aims: To find a practical modality to reduce 4-hydroxynonenal in PN and assess in vivo the impact of PN containing low 4-hydroxynonenal concentration. Methods: Six modalities of delivering PN were compared for the in vitro generation of peroxides and 4-hydroxynonenal: 1) MV-AA-L: light-protected (-L) solution containing multivitamin (MV) mixed with amino acids + dextrose (AA); 2) MV-AA+L: MV-AA without photo-protection (+L); 3) MV-LIP+L: MV mixed with lipid emulsion (LIP). LIP was a) Intralipid20%(®) or b) Omegaven(®). Hepatic markers of oxidative stress (glutathione, F(2α)-isoprostanes, GS-HNE) and inflammation (mRNA of TNF-α and IL-1) were measured in newborn guinea pigs infused during 4-days with MV-AA+L compounded with Intralipid20%(®) or Omegaven(®). Results: Hydroperoxides and 4-hydroxynonenal were the lowest in MV-AA-L and the highest in MV-LIP+L. MV-AA+L with Omegaven(®) was associated with the lowest levels of markers of oxidative stress and inflammation. Conclusion: Compared to Intralipid20%(®), Omegaven(®) reduces oxidative stress associated with PN and prevents liver inflammation. These findings offer an alternative strategy to light protection of PN, which in the clinical setting is a cumbersome modality.
MeSH term(s)	Aldehydes/metabolism ; Amino Acids/administration & dosage ; Animals ; Emulsions/administration & dosage ; Fish Oils/administration & dosage ; Glucose/administration & dosage ; Glutathione/metabolism ; Guinea Pigs ; Hydrogen Peroxide/metabolism ; Inflammation/drug therapy ; Inflammation/prevention & control ; Interleukin-1/metabolism ; Liver/metabolism ; Liver/pathology ; Oxidative Stress/drug effects ; Parenteral Nutrition Solutions/administration & dosage ; Parenteral Nutrition, Total/methods ; Phospholipids/administration & dosage ; Soybean Oil/administration & dosage ; Tumor Necrosis Factor-alpha/metabolism ; Vitamins/administration & dosage
Chemical Substances	Aldehydes ; Amino Acids ; Emulsions ; Fish Oils ; Interleukin-1 ; Parenteral Nutrition Solutions ; Phospholipids ; Tumor Necrosis Factor-alpha ; Vitamins ; soybean oil, phospholipid emulsion ; Soybean Oil (8001-22-7) ; Hydrogen Peroxide (BBX060AN9V) ; Glutathione (GAN16C9B8O) ; Glucose (IY9XDZ35W2) ; 4-hydroxy-2-nonenal (K1CVM13F96) ; Omegaven (XGF7L72M0F)
Language	English
Publishing date	2012-01-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604812-2
ISSN	1532-1983 ; 0261-5614
ISSN (online)	1532-1983
ISSN	0261-5614
DOI	10.1016/j.clnu.2011.12.012
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Article ; Online: MicroRNA signatures in vitreous humour and plasma of patients with exudative AMD.

Ménard, Catherine / Rezende, Flavio A / Miloudi, Khalil / Wilson, Ariel / Tétreault, Nicolas / Hardy, Pierre / SanGiovanni, John Paul / De Guire, Vincent / Sapieha, Przemyslaw

Oncotarget

2016 Volume 7, Issue 15, Page(s) 19171–19184

Abstract: 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 ... ...

Abstract	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 miRNAs in the vitreous humour and plasma of patients with NV AMD. We identified a disease-associated increase in miR-146a and a decrease in miR-106b and miR-152 in the vitreous humour which was reproducible in plasma. Moreover, miR-146a/miR-106b ratios discriminated patients with NV AMD with an area under the Receiver Operating Characteristic curve (ROC AUC) of 0,977 in vitreous humour and 0,915 in plasma suggesting potential for a blood-based diagnostic. Furthermore, using the AMD Gene Consortium (AGC) we mapped a NV AMD-associated SNP (rs1063320) in a binding site for miR-152-3p in the HLA-G gene. The relationship between our detected miRNAs and NV AMD related genes was also investigated using gene sets derived from the Ingenuity Pathway Analysis (IPA). To our knowledge, our study is the first to correlate vitreal and plasma miRNA signatures with NV AMD, highlighting potential future worth as biomarkers and providing insight on NV AMD pathogenesis.
Language	English
Publishing date	2016-04-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.8280
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Article ; Online: Senescence-associated secretory phenotype contributes to pathological angiogenesis in retinopathy.

Oubaha, Malika / Miloudi, Khalil / Dejda, Agnieszka / Guber, Vera / Mawambo, Gaëlle / Germain, Marie-Anne / Bourdel, Guillaume / Popovic, Natalija / Rezende, Flavio A / Kaufman, Randal J / Mallette, Frédérick A / Sapieha, Przemyslaw

Science translational medicine

2016 Volume 8, Issue 362, Page(s) 362ra144

Abstract: Pathological angiogenesis is the hallmark of diseases such as cancer and retinopathies. Although tissue hypoxia and inflammation are recognized as central drivers of vessel growth, relatively little is known about the process that bridges the two. In a ... ...

Abstract	Pathological angiogenesis is the hallmark of diseases such as cancer and retinopathies. Although tissue hypoxia and inflammation are recognized as central drivers of vessel growth, relatively little is known about the process that bridges the two. In a mouse model of ischemic retinopathy, we found that hypoxic regions of the retina showed only modest rates of apoptosis despite severely compromised metabolic supply. Using transcriptomic analysis and inducible loss-of-function genetics, we demonstrated that ischemic retinal cells instead engage the endoplasmic reticulum stress inositol-requiring enzyme 1α (IRE1α) pathway that, through its endoribonuclease activity, induces a state of senescence in which cells adopt a senescence-associated secretory phenotype (SASP). We also detected SASP-associated cytokines (plasminogen activator inhibitor 1, interleukin-6, interleukin-8, and vascular endothelial growth factor) in the vitreous humor of patients suffering from proliferative diabetic retinopathy. Therapeutic inhibition of the SASP through intravitreal delivery of metformin or interference with effectors of senescence (semaphorin 3A or IRE1α) in mice reduced destructive retinal neovascularization in vivo. We conclude that the SASP contributes to pathological vessel growth, with ischemic retinal cells becoming prematurely senescent and secreting inflammatory cytokines that drive paracrine senescence, exacerbate destructive angiogenesis, and hinder reparative vascular regeneration. Reversal of this process may be therapeutically beneficial.
Language	English
Publishing date	2016-10-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	2518854-9
ISSN	1946-6242 ; 1946-6234
ISSN (online)	1946-6242
ISSN	1946-6234
DOI	10.1126/scitranslmed.aaf9440
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