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Article ; Online: From the vulnerable plaque to the vulnerable patient: Current concepts in atherosclerosis.

Sage, Andrew P / Antoniades, Charalambos

2021 Volume 178, Issue 11, Page(s) 2165–2167

MeSH term(s)	Atherosclerosis ; Humans ; Plaque, Atherosclerotic
Language	English
Publishing date	2021-02-10
Publishing country	England
Document type	Editorial
ZDB-ID	80081-8
ISSN	1476-5381 ; 0007-1188
ISSN (online)	1476-5381
ISSN	0007-1188
DOI	10.1111/bph.15347
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Article ; Online: Calcioprotein particles: The LDL of vascular calcification?

Sage, Andrew P

Atherosclerosis

2016 Volume 251, Page(s) 516–517

MeSH term(s)	Calcinosis ; Humans ; Muscle, Smooth, Vascular ; Vascular Calcification
Language	English
Publishing date	2016
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	80061-2
ISSN	1879-1484 ; 0021-9150
ISSN (online)	1879-1484
ISSN	0021-9150
DOI	10.1016/j.atherosclerosis.2016.06.032
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Article ; Online: Readapting the adaptive immune response - therapeutic strategies for atherosclerosis.

Sage, Andrew P / Mallat, Ziad

British journal of pharmacology

2017 Volume 174, Issue 22, Page(s) 3926–3939

Abstract: Cardiovascular diseases remain a major global health issue, with the development of atherosclerosis as a major underlying cause. Our treatment of cardiovascular disease has improved greatly over the past three decades, but much remains to be done reduce ... ...

Abstract	Cardiovascular diseases remain a major global health issue, with the development of atherosclerosis as a major underlying cause. Our treatment of cardiovascular disease has improved greatly over the past three decades, but much remains to be done reduce disease burden. Current priorities include reducing atherosclerosis advancement to clinically significant stages and preventing plaque rupture or erosion. Inflammation and involvement of the adaptive immune system influences all these aspects and therefore is one focus for future therapeutic development. The atherosclerotic vascular wall is now recognized to be invaded from both sides (arterial lumen and adventitia), for better or worse, by the adaptive immune system. Atherosclerosis is also affected at several stages by adaptive immune responses, overall providing many opportunities to target these responses and to reduce disease progression. Protective influences that may be defective in diseased individuals include humoral responses to modified LDL and regulatory T cell responses. There are many strategies in development to boost these pathways in humans, including vaccine-based therapies. The effects of various existing adaptive immune targeting therapies, such as blocking critical co-stimulatory pathways or B cell depletion, on cardiovascular disease are beginning to emerge with important consequences for both autoimmune disease patients and the potential for wider use of such therapies. Entering the translation phase for adaptive immune targeting therapies is an exciting and promising prospect. Linked articles: This article is part of a themed section on Targeting Inflammation to Reduce Cardiovascular Disease Risk. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.22/issuetoc and http://onlinelibrary.wiley.com/doi/10.1111/bcp.v82.4/issuetoc.
MeSH term(s)	Adaptive Immunity ; Animals ; Atherosclerosis/drug therapy ; Atherosclerosis/immunology ; Humans
Language	English
Publishing date	2017-02-01
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	80081-8
ISSN	1476-5381 ; 0007-1188
ISSN (online)	1476-5381
ISSN	0007-1188
DOI	10.1111/bph.13700
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Article ; Online: Sialyltransferase activity and atherosclerosis.

Sage, Andrew P / Mallat, Ziad

Circulation research

2014 Volume 114, Issue 6, Page(s) 935–937

MeSH term(s)	Animals ; Atherosclerosis/enzymology ; Chemokine CCL5/physiology ; Female ; Leukocyte Rolling/physiology ; Male ; Myeloid Cells/pathology ; Sialyltransferases/deficiency
Chemical Substances	Ccl5 protein, mouse ; Chemokine CCL5 ; Sialyltransferases (EC 2.4.99.-) ; beta-galactoside alpha-2,3-sialyltransferase (EC 2.4.99.4)
Language	English
Publishing date	2014-03-14
Publishing country	United States
Document type	Comment ; Editorial ; Research Support, Non-U.S. Gov't
ZDB-ID	80100-8
ISSN	1524-4571 ; 0009-7330 ; 0931-6876
ISSN (online)	1524-4571
ISSN	0009-7330 ; 0931-6876
DOI	10.1161/CIRCRESAHA.114.303480
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Article ; Online: The Sunlight: A New Immunomodulatory Approach of Atherosclerosis.

Ait-Oufella, Hafid / Sage, Andrew P

Arteriosclerosis, thrombosis, and vascular biology

2016 Volume 37, Issue 1, Page(s) 7–9

MeSH term(s)	Atherosclerosis ; Autoimmunity ; Humans ; Sunlight
Language	English
Publishing date	2016-12-28
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	1221433-4
ISSN	1524-4636 ; 1079-5642
ISSN (online)	1524-4636
ISSN	1079-5642
DOI	10.1161/ATVBAHA.116.308637
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Article ; Online: Immunobiology of a rationally-designed AAV2 capsid following intravitreal delivery in mice.

Whitehead, Michael / Sage, Andrew / Burgoyne, Tom / Osborne, Andrew / Yu-Wai-Man, Patrick / Martin, Keith R

Gene therapy

2023 Volume 30, Issue 9, Page(s) 723–735

Abstract: Adeno-associated virus serotype 2 (AAV2) is a viral vector that can be used to deliver therapeutic genes to diseased cells in the retina. One strategy for altering AAV2 vectors involves the mutation of phosphodegron residues, which are thought to be ... ...

Abstract	Adeno-associated virus serotype 2 (AAV2) is a viral vector that can be used to deliver therapeutic genes to diseased cells in the retina. One strategy for altering AAV2 vectors involves the mutation of phosphodegron residues, which are thought to be phosphorylated/ubiquitinated in the cytosol, facilitating degradation of the vector and the inhibition of transduction. As such, mutation of phosphodegron residues have been correlated with increased transduction of target cells, however, an assessment of the immunobiology of wild-type and phosphodegron mutant AAV2 vectors following intravitreal (IVT) delivery to immunocompetent animals is lacking in the current literature. In this study, we show that IVT of a triple phosphodegron mutant AAV2 capsid is associated with higher levels of humoral immune activation, infiltration of CD4 and CD8 T-cells into the retina, generation of splenic germinal centre reactions, activation of conventional dendritic cell subsets, and elevated retinal gliosis compared to wild-type AAV2 capsids. However, we did not detect significant changes in electroretinography arising after vector administration. We also demonstrate that the triple AAV2 mutant capsid is less susceptible to neutralisation by soluble heparan sulphate and anti-AAV2 neutralising antibodies, highlighting a possible utility for the vector in terms of circumventing pre-existing humoral immunity. In summary, the present study highlights novel aspects of rationally-designed vector immunobiology, which may be relevant to their application in preclinical and clinical settings.
MeSH term(s)	Mice ; Animals ; Capsid/metabolism ; Serogroup ; Transduction, Genetic ; Capsid Proteins/genetics ; Capsid Proteins/metabolism ; Parvovirinae/genetics ; Dependovirus/metabolism ; Genetic Vectors/genetics
Chemical Substances	Capsid Proteins
Language	English
Publishing date	2023-06-29
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1191036-7
ISSN	1476-5462 ; 0969-7128
ISSN (online)	1476-5462
ISSN	0969-7128
DOI	10.1038/s41434-023-00409-x
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Zs.A 3991: Show issues

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Article ; Online: β-Carbolines found in cigarette smoke elevate intracranial self-stimulation thresholds in rats.

Harris, Andrew C / Muelken, Peter / LeSage, Mark G

Pharmacology, biochemistry, and behavior

2020 Volume 198, Page(s) 173041

Abstract: Identifying novel constituents that contribute to tobacco addiction is essential for developing more effective treatments and informing FDA regulation of tobacco products. While preclinical data indicate that monoamine oxidase (MAO) inhibitors can have ... ...

Abstract	Identifying novel constituents that contribute to tobacco addiction is essential for developing more effective treatments and informing FDA regulation of tobacco products. While preclinical data indicate that monoamine oxidase (MAO) inhibitors can have abuse liability or potentiate the addiction-related effects of nicotine, most of these studies have used clinical MAO inhibitors (e.g., tranylcypromine) that are not present in cigarette smoke. The primary goal of this study was to evaluate the abuse potential of the β-carbolines harmane, norharmane, and harmine - MAO inhibitors that are found in cigarette smoke - in an intracranial self-simulation (ICSS) model in rats. A secondary goal was to evaluate the ability of norharmane to influence nicotine's acute effects on ICSS. None of the β-carbolines lowered ICSS thresholds at any dose studied when administered alone, suggesting a lack of abuse liability. Rather, all three β-carbolines produced dose-dependent elevations in ICSS thresholds, indicating aversive/anhedonic effects. Harmane and harmine also elevated ICSS response latencies, suggesting a disruption of motor function, albeit with reduced potency compared to their ICSS threshold-elevating effects. Norharmane (2.5 mg/kg) modestly attenuated the effects of nicotine on ICSS thresholds. Our findings indicate that these β-carbolines produced only aversive/anhedonic effects in an ICSS model when administered alone, and that norharmane unexpectedly attenuated nicotines acute effects on ICSS. Future work evaluating the addiction-related effects of nicotine combined with these and other MAO inhibitors present in smoke may be useful for understanding the role of MAO inhibition in tobacco addiction and informing FDA tobacco regulation.
MeSH term(s)	Animals ; Behavior, Addictive ; Brain/drug effects ; Carbolines/chemistry ; Carbolines/pharmacology ; Female ; Harmine/analogs & derivatives ; Harmine/pharmacology ; Male ; Monoamine Oxidase Inhibitors/chemistry ; Monoamine Oxidase Inhibitors/pharmacology ; Motor Activity/drug effects ; Nicotine/pharmacology ; Rats ; Rats, Sprague-Dawley ; Reinforcement, Psychology ; Self Stimulation/drug effects ; Smoke/adverse effects ; Smoke/analysis ; Nicotiana/adverse effects ; Nicotiana/chemistry
Chemical Substances	Carbolines ; Monoamine Oxidase Inhibitors ; Smoke ; Harmine (4FHH5G48T7) ; Nicotine (6M3C89ZY6R) ; harman (82D6J0535P) ; norharman (94HMA1I78O)
Language	English
Publishing date	2020-09-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	191042-5
ISSN	1873-5177 ; 0091-3057
ISSN (online)	1873-5177
ISSN	0091-3057
DOI	10.1016/j.pbb.2020.173041
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Article ; Online: Multiple potential roles for B cells in atherosclerosis.

Sage, Andrew P / Mallat, Ziad

Annals of medicine

2014 Volume 46, Issue 5, Page(s) 297–303

Abstract: The development of atherosclerosis is the major etiological factor causing cardiovascular disease and constitutes a lipid-induced, chronic inflammatory and autoimmune disease of the large arteries. A long-standing view of the protective role of B cells ... ...

Abstract	The development of atherosclerosis is the major etiological factor causing cardiovascular disease and constitutes a lipid-induced, chronic inflammatory and autoimmune disease of the large arteries. A long-standing view of the protective role of B cells in atherosclerosis has been challenged by recent studies using B cell depletion in animal models. Whereas complete B cell deficiency increases atherosclerosis, depletion of B2 but not B1 cells reduces atherosclerosis. This has led to a re-evaluation of the multiple potential pathways by which B cells can regulate atherosclerosis, and the apparent opposing roles of B1 and B2 cells. B cells, in addition to having the unique ability to produce antibodies, are now recognized to play a number of important roles in the immune system, including cytokine production and direct regulation of T cell responses. This review summarizes current knowledge on B cell subsets and functions, and how these could distinctly influence atherosclerosis development.
MeSH term(s)	Animals ; Atherosclerosis/immunology ; Atherosclerosis/physiopathology ; B-Lymphocyte Subsets/immunology ; B-Lymphocytes/immunology ; Cytokines/immunology ; Disease Models, Animal ; Humans ; T-Lymphocytes/immunology
Chemical Substances	Cytokines
Language	English
Publishing date	2014-05-09
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1004226-x
ISSN	1365-2060 ; 1651-2219 ; 0785-3890 ; 1743-1387
ISSN (online)	1365-2060 ; 1651-2219
ISSN	0785-3890 ; 1743-1387
DOI	10.3109/07853890.2014.900272
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Article ; Online: Validation of the structured interview section of the penn computerized adaptive test for neurocognitive and clinical psychopathology assessment (CAT GOASSESS).

Zoupou, Eirini / Moore, Tyler M / Kennedy, Kelly P / Calkins, Monica E / Gorgone, Alesandra / Sandro, Akira Di / Rush, Sage / Lopez, Katherine C / Ruparel, Kosha / Daryoush, Tarlan / Okoyeh, Paul / Savino, Andrew / Troyan, Scott / Wolf, Daniel H / Scott, J Cobb / Gur, Raquel E / Gur, Ruben C

Psychiatry research

2024 Volume 335, Page(s) 115862

Abstract: Large-scale studies and burdened clinical settings require precise, efficient measures that assess multiple domains of psychopathology. Computerized adaptive tests (CATs) can reduce administration time without compromising data quality. We examined ... ...

Abstract	Large-scale studies and burdened clinical settings require precise, efficient measures that assess multiple domains of psychopathology. Computerized adaptive tests (CATs) can reduce administration time without compromising data quality. We examined feasibility and validity of an adaptive psychopathology measure, GOASSESS, in a clinical community-based sample (N = 315; ages 18-35) comprising three groups: healthy controls, psychosis, mood/anxiety disorders. Assessment duration was compared between the Full and CAT GOASSESS. External validity was tested by comparing how the CAT and Full versions related to demographic variables, study group, and socioeconomic status. The relationships between scale scores and criteria were statistically compared within a mixed-model framework to account for dependency between relationships. Convergent validity was assessed by comparing scores of the CAT and the Full GOASSESS using Pearson correlations. The CAT GOASSESS reduced interview duration by more than 90 % across study groups and preserved relationships to external criteria and demographic variables as the Full GOASSESS. All CAT GOASSESS scales could replace those of the Full instrument. Overall, the CAT GOASSESS showed acceptable psychometric properties and demonstrated feasibility by markedly reducing assessment time compared to the Full GOASSESS. The adaptive version could be used in large-scale studies or clinical settings for intake screening.
MeSH term(s)	Humans ; Anxiety Disorders/psychology ; Psychopathology ; Mood Disorders/diagnosis ; Psychotic Disorders ; Anxiety ; Psychometrics ; Reproducibility of Results
Language	English
Publishing date	2024-03-15
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	445361-x
ISSN	1872-7123 ; 1872-7506 ; 0925-4927 ; 0165-1781
ISSN (online)	1872-7123 ; 1872-7506
ISSN	0925-4927 ; 0165-1781
DOI	10.1016/j.psychres.2024.115862
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Article: Cigarette Smoke Extract, but Not Electronic Cigarette Aerosol Extract, Inhibits Monoamine Oxidase

Harris, Andrew C / Muelken, Peter / Alcheva, Aleksandra / Stepanov, Irina / LeSage, Mark G

Frontiers in neuroscience

2022 Volume 16, Page(s) 868088

Abstract: Conventional tobacco cigarettes appear to have greater abuse liability than non-combusted products such as electronic cigarettes (ECs) and nicotine replacement therapy (NRT). This may be due to the higher levels of behaviorally active non-nicotine ... ...

Abstract	Conventional tobacco cigarettes appear to have greater abuse liability than non-combusted products such as electronic cigarettes (ECs) and nicotine replacement therapy (NRT). This may be due to the higher levels of behaviorally active non-nicotine constituents [e.g., monoamine oxidase (MAO) inhibitors such as β-carbolines] in cigarette smoke (CS) compared to non-combusted products. To evaluate this hypothesis, the current studies compared the relative abuse liability of CS and EC aerosol extracts containing nicotine and a range of non-nicotine constituents to that of nicotine alone (NRT analog) using intracranial self-stimulation (ICSS) in rats. Effects of formulations on brain MAO activity
Language	English
Publishing date	2022-05-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2022.868088
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