LIVIVO - Search results -

Search results

Result 1 - 10 of total 32

Search options

Article: Crosstalk Between Cholesterol, ABC Transporters, and PIP2 in Inflammation and Atherosclerosis.

Gulshan, Kailash

Advances in experimental medicine and biology

2023 Volume 1422, Page(s) 353–377

Abstract: The lowering of plasma low-density lipoprotein cholesterol (LDL-C) is an easily achievable and highly reliable modifiable risk factor for preventing cardiovascular disease (CVD), as validated by the unparalleled success of statins in the last three ... ...

Abstract	The lowering of plasma low-density lipoprotein cholesterol (LDL-C) is an easily achievable and highly reliable modifiable risk factor for preventing cardiovascular disease (CVD), as validated by the unparalleled success of statins in the last three decades. However, the 2021 American Heart Association (AHA) statistics show a worrying upward trend in CVD deaths, calling into question the widely held belief that statins and available adjuvant therapies can fully resolve the CVD problem. Human biomarker studies have shown that indicators of inflammation, such as human C-reactive protein (hCRP), can serve as a reliable risk predictor for CVD, independent of all traditional risk factors. Oxidized cholesterol mediates chronic inflammation and promotes atherosclerosis, while anti-inflammatory therapies, such as an anti-interleukin-1 beta (anti-IL-1β) antibody, can reduce CVD in humans. Cholesterol removal from artery plaques, via an athero-protective reverse cholesterol transport (RCT) pathway, can dampen inflammation. Phosphatidylinositol 4,5-bisphosphate (PIP2) plays a role in RCT by promoting adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1)-mediated cholesterol efflux from arterial macrophages. Cholesterol crystals activate the nod-like receptor family pyrin domain containing 3 (Nlrp3) inflammasome in advanced atherosclerotic plaques, leading to IL-1β release in a PIP2-dependent fashion. PIP2 thus is a central player in CVD pathogenesis, serving as a critical link between cellular cholesterol levels, ATP-binding cassette (ABC) transporters, and inflammasome-induced IL-1β release.
MeSH term(s)	Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Inflammasomes/metabolism ; ATP-Binding Cassette Transporters/metabolism ; Atherosclerosis/metabolism ; Cholesterol/metabolism ; Plaque, Atherosclerotic ; Inflammation/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
Chemical Substances	Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Inflammasomes ; ATP-Binding Cassette Transporters ; Cholesterol (97C5T2UQ7J) ; NLR Family, Pyrin Domain-Containing 3 Protein
Language	English
Publishing date	2023-03-29
Publishing country	United States
Document type	Journal Article
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/978-3-031-21547-6_13
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Article: Editorial: Decoding complexity: new insights into the cellular and molecular mechanisms of cardiovascular and metabolic diseases.

Liu, Chia-Feng / Gulshan, Kailash / Basu, Jayati / Sun, Yu-Yo

Frontiers in cardiovascular medicine

2023 Volume 10, Page(s) 1239170

Language	English
Publishing date	2023-07-10
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2781496-8
ISSN	2297-055X
ISSN	2297-055X
DOI	10.3389/fcvm.2023.1239170
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Disulfiram Reduces Atherosclerosis and Enhances Efferocytosis, Autophagy, and Atheroprotective Gut Microbiota in Hyperlipidemic Mice.

Traughber, C Alicia / Timinski, Kara / Prince, Ashutosh / Bhandari, Nilam / Neupane, Kalash / Khan, Mariam R / Opoku, Esther / Opoku, Emmanuel / Brubaker, Gregory / Shin, Junchul / Hong, Junyoung / Kanuri, Babunageswararao / Ertugral, Elif G / Nagareddy, Prabhakara R / Kothapalli, Chandrasekhar R / Cherepanova, Olga / Smith, Jonathan D / Gulshan, Kailash

Journal of the American Heart Association

2024 Volume 13, Issue 8, Page(s) e033881

Abstract: Background: Pyroptosis executor GsdmD (gasdermin D) promotes atherosclerosis in mice and humans. Disulfiram was recently shown to potently inhibit GsdmD, but the in vivo efficacy and mechanism of disulfiram's antiatherosclerotic activity is yet to be ... ...

Abstract	Background: Pyroptosis executor GsdmD (gasdermin D) promotes atherosclerosis in mice and humans. Disulfiram was recently shown to potently inhibit GsdmD, but the in vivo efficacy and mechanism of disulfiram's antiatherosclerotic activity is yet to be explored. Methods and results: We used human/mouse macrophages, endothelial cells, and smooth muscle cells and a hyperlipidemic mouse model of atherosclerosis to determine disulfiram antiatherosclerotic efficacy and mechanism. The effects of disulfiram on several atheroprotective pathways such as autophagy, efferocytosis, phagocytosis, and gut microbiota were determined. Atomic force microscopy was used to determine the effects of disulfiram on the biophysical properties of the plasma membrane of macrophages. Disulfiram-fed hyperlipidemic apolipoprotein E Conclusions: Taken together, our data show that disulfiram can simultaneously modulate several atheroprotective pathways in a GsdmD-dependent as well as GsdmD-independent manner.
MeSH term(s)	Male ; Female ; Mice ; Humans ; Animals ; Disulfiram ; Efferocytosis ; Endothelial Cells/metabolism ; Gastrointestinal Microbiome ; Atherosclerosis/drug therapy ; Atherosclerosis/genetics ; Atherosclerosis/prevention & control ; Autophagy
Chemical Substances	Disulfiram (TR3MLJ1UAI)
Language	English
Publishing date	2024-04-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2653953-6
ISSN	2047-9980 ; 2047-9980
ISSN (online)	2047-9980
ISSN	2047-9980
DOI	10.1161/JAHA.123.033881
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Myeloid-cell-specific role of Gasdermin D in promoting lung cancer progression in mice.

Traughber, C Alicia / Deshpande, Gauravi M / Neupane, Kalash / Bhandari, Nilam / Khan, Mariam R / McMullen, Megan R / Swaidani, Shadi / Opoku, Emmanuel / Muppala, Santoshi / Smith, Jonathan D / Nagy, Laura E / Gulshan, Kailash

iScience

2023 Volume 26, Issue 2, Page(s) 106076

Abstract: The activities of the NLRP3 and AIM2 inflammasomes and Gasdermin D (GsdmD) are implicated in lung cancer pathophysiology but it's not clear if their contributions promote or retard lung cancer progression. Using a metastatic Lewis lung carcinoma (LLC) ... ...

Abstract	The activities of the NLRP3 and AIM2 inflammasomes and Gasdermin D (GsdmD) are implicated in lung cancer pathophysiology but it's not clear if their contributions promote or retard lung cancer progression. Using a metastatic Lewis lung carcinoma (LLC) cell model, we show that GsdmD knockout (GsdmD
Language	English
Publishing date	2023-01-31
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.106076
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Impavido attenuates inflammation, reduces atherosclerosis, and alters gut microbiota in hyperlipidemic mice.

Traughber, C Alicia / Iacano, Amanda J / Neupane, Kalash / Khan, Mariam R / Opoku, Emmanuel / Nunn, Tina / Prince, Ashutosh / Sangwan, Naseer / Hazen, Stanley L / Smith, Jonathan D / Gulshan, Kailash

iScience

2023 Volume 26, Issue 4, Page(s) 106453

Abstract: Impavido (Miltefosine) is an FDA-approved drug for treating leishmaniasis and primary amebic meningoencephalitis. We have shown previously that Miltefosine increased cholesterol release and dampened Nlrp3 inflammasome assembly in macrophages. Here, we ... ...

Abstract	Impavido (Miltefosine) is an FDA-approved drug for treating leishmaniasis and primary amebic meningoencephalitis. We have shown previously that Miltefosine increased cholesterol release and dampened Nlrp3 inflammasome assembly in macrophages. Here, we show that Miltefosine reduced LPS-induced choline uptake by macrophages, and attenuated Nlrp3 inflammasome assembly in mice. Miltefosine-fed mice showed reduced plasma IL-1β in a polymicrobial cecal slurry model of systemic inflammation. Miltefosine-fed mice showed increased reverse cholesterol transport to the plasma, liver, and feces. Hyperlipidemic apoE
Language	English
Publishing date	2023-03-20
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.106453
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: First eight residues of apolipoprotein A-I mediate the C-terminus control of helical bundle unfolding and its lipidation.

Brubaker, Gregory / Lorkowski, Shuhui W / Gulshan, Kailash / Hazen, Stanley L / Gogonea, Valentin / Smith, Jonathan D

PloS one

2020 Volume 15, Issue 1, Page(s) e0221915

Abstract: The crystal structure of a C-terminal deletion of apolipoprotein A-I (apoA1) shows a large helical bundle structure in the amino half of the protein, from residues 8 to 115. Using site directed mutagenesis, guanidine or thermal denaturation, cell free ... ...

Abstract	The crystal structure of a C-terminal deletion of apolipoprotein A-I (apoA1) shows a large helical bundle structure in the amino half of the protein, from residues 8 to 115. Using site directed mutagenesis, guanidine or thermal denaturation, cell free liposome clearance, and cellular ABCA1-mediated cholesterol efflux assays, we demonstrate that apoA1 lipidation can occur when the thermodynamic barrier to this bundle unfolding is lowered. The absence of the C-terminus renders the bundle harder to unfold resulting in loss of apoA1 lipidation that can be reversed by point mutations, such as Trp8Ala, and by truncations as short as 8 residues in the amino terminus, both of which facilitate helical bundle unfolding. Locking the bundle via a disulfide bond leads to loss of apoA1 lipidation. We propose a model in which the C-terminus acts on the N-terminus to destabilize this helical bundle. Upon lipid binding to the C-terminus, Trp8 is displaced from its interaction with Phe57, Arg61, Leu64, Val67, Phe71, and Trp72 to destabilize the bundle. However, when the C-terminus is deleted, Trp8 cannot be displaced, the bundle cannot unfold, and apoA1 cannot be lipidated.
MeSH term(s)	ATP Binding Cassette Transporter 1/chemistry ; ATP Binding Cassette Transporter 1/genetics ; ATP-Binding Cassette Transporters/genetics ; Animals ; Apolipoprotein A-I/chemistry ; Apolipoprotein A-I/genetics ; Biological Transport/genetics ; Circular Dichroism ; Crystallography, X-Ray ; Humans ; Kinetics ; Lipid Metabolism/genetics ; Lipids/chemistry ; Lipids/genetics ; Mice ; Mutagenesis, Site-Directed ; Protein Binding ; Protein Structure, Secondary ; Protein Unfolding ; RAW 264.7 Cells ; Sequence Deletion/genetics
Chemical Substances	ABCA1 protein, human ; ATP Binding Cassette Transporter 1 ; ATP-Binding Cassette Transporters ; Apolipoprotein A-I ; Lipids
Language	English
Publishing date	2020-01-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0221915
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Biomarkers of Cardiovascular Disease.

Huang, Ying / Gulshan, Kailash / Nguyen, Truc / Wu, Yuping

Disease markers

2017 Volume 2017, Page(s) 8208609

MeSH term(s)	Biomarkers/metabolism ; Cardiovascular Diseases/diagnosis ; Cardiovascular Diseases/metabolism ; Early Diagnosis ; Humans ; Prognosis
Chemical Substances	Biomarkers
Language	English
Publishing date	2017-11-07
Publishing country	United States
Document type	Editorial ; Introductory Journal Article
ZDB-ID	604951-5
ISSN	1875-8630 ; 0278-0240
ISSN (online)	1875-8630
ISSN	0278-0240
DOI	10.1155/2017/8208609
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1856: 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)
Einzelsignatur: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: V-ATPase (Vacuolar ATPase) Activity Required for ABCA1 (ATP-Binding Cassette Protein A1)-Mediated Cholesterol Efflux.

Lorkowski, Shuhui Wang / Brubaker, Gregory / Gulshan, Kailash / Smith, Jonathan D

Arteriosclerosis, thrombosis, and vascular biology

2018 Volume 38, Issue 11, Page(s) 2615–2625

Abstract: Objective- We have shown that ABCA1 (ATP-binding cassette protein A1) mediates unfolding of the apoA1 (apolipoprotein A1) N-terminal helical hairpin during apoA1 lipidation. Others have shown that an acidic pH exposes the hydrophobic surface of apoA1. We ...

Abstract	Objective- We have shown that ABCA1 (ATP-binding cassette protein A1) mediates unfolding of the apoA1 (apolipoprotein A1) N-terminal helical hairpin during apoA1 lipidation. Others have shown that an acidic pH exposes the hydrophobic surface of apoA1. We postulated that the V-ATPase (vacuolar ATPase) proton pump facilitates apoA1 unfolding and promotes ABCA1-mediated cholesterol efflux. Approach and Results- We found that V-ATPase inhibitors dose-dependently decreased ABCA1-mediated cholesterol efflux to apoA1 in baby hamster kidney cells and RAW264.7 cells; and similarly, siRNA knockdown of ATP6V
MeSH term(s)	ATP Binding Cassette Transporter 1/metabolism ; Animals ; Apolipoprotein A-I/chemistry ; Apolipoprotein A-I/metabolism ; Cell Membrane/enzymology ; Cholesterol/metabolism ; Cricetinae ; Enzyme Inhibitors/pharmacology ; Hydrogen-Ion Concentration ; Macrolides/pharmacology ; Macrophages/drug effects ; Macrophages/enzymology ; Mice ; Protein Transport ; Protein Unfolding ; RAW 264.7 Cells ; Vacuolar Proton-Translocating ATPases/antagonists & inhibitors ; Vacuolar Proton-Translocating ATPases/genetics ; Vacuolar Proton-Translocating ATPases/metabolism
Chemical Substances	ABCA1 protein, human ; ABCA1 protein, mouse ; APOA1 protein, human ; ATP Binding Cassette Transporter 1 ; Apolipoprotein A-I ; Enzyme Inhibitors ; Macrolides ; bafilomycin A1 (88899-55-2) ; Cholesterol (97C5T2UQ7J) ; Vacuolar Proton-Translocating ATPases (EC 3.6.1.-)
Language	English
Publishing date	2018-10-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1221433-4
ISSN	1524-4636 ; 1079-5642
ISSN (online)	1524-4636
ISSN	1079-5642
DOI	10.1161/ATVBAHA.118.311814
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1705: 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)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Gasdermin D Mediates Inflammation-Induced Defects in Reverse Cholesterol Transport and Promotes Atherosclerosis.

Opoku, Emmanuel / Traughber, Cynthia Alicia / Zhang, David / Iacano, Amanda J / Khan, Mariam / Han, Juying / Smith, Jonathan D / Gulshan, Kailash

Frontiers in cell and developmental biology

2021 Volume 9, Page(s) 715211

Abstract: Activation of inflammasomes, such as Nlrp3 and AIM2, can exacerbate atherosclerosis in mice and humans. Gasdermin D (GsdmD) serves as a final executor of inflammasome activity, by generating membrane pores for the release of mature Interleukin-1beta (IL- ... ...

Abstract	Activation of inflammasomes, such as Nlrp3 and AIM2, can exacerbate atherosclerosis in mice and humans. Gasdermin D (GsdmD) serves as a final executor of inflammasome activity, by generating membrane pores for the release of mature Interleukin-1beta (IL-1β). Inflammation dampens reverse cholesterol transport (RCT) and promotes atherogenesis, while anti-IL-1β antibodies were shown to reduce cardiovascular disease in humans. Though Nlrp3/AIM2 and IL-1β nexus is an emerging atherogenic pathway, the direct role of GsdmD in atherosclerosis is not yet fully clear. Here, we used
Language	English
Publishing date	2021-07-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2021.715211
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Miltefosine increases macrophage cholesterol release and inhibits NLRP3-inflammasome assembly and IL-1β release.

Iacano, Amanda J / Lewis, Harvey / Hazen, Jennie E / Andro, Heather / Smith, Jonathan D / Gulshan, Kailash

Scientific reports

2019 Volume 9, Issue 1, Page(s) 11128

Abstract: Miltefosine is an FDA approved oral drug for treating cutaneous and visceral leishmaniasis. Leishmania is a flagellated protozoa, which infects and differentiates in macrophages. Here, we studied the effects of Miltefosine on macrophage's lipid ... ...

Abstract	Miltefosine is an FDA approved oral drug for treating cutaneous and visceral leishmaniasis. Leishmania is a flagellated protozoa, which infects and differentiates in macrophages. Here, we studied the effects of Miltefosine on macrophage's lipid homeostasis, autophagy, and NLRP3 inflammasome assembly/activity. Miltefosine treatment conferred multiple effects on macrophage lipid homeostasis leading to increased cholesterol release from cells, increased lipid-raft disruption, decreased phosphatidylserine (PS) flip from the cell-surface, and redistribution of phosphatidylinositol 4,5-bisphosphate (PIP2) from the plasma membrane to actin rich regions in the cells. Enhanced basal autophagy, lipophagy and mitophagy was observed in cells treated with Miltefosine vs. control. Miltefosine treated cells showed marked increased in phosphorylation of kinases involved in autophagy induction such as; Adenosine monophosphate-activated protein kinase (AMPK) and Unc-51 like autophagy activating kinase (ULK1). The Toll like receptor (TLR) signaling pathway was blunted by Miltefosine treatment, resulting in decreased TLR4 recruitment to cell-surface and ~75% reduction in LPS induced pro-IL-1β mRNA levels. Miltefosine reduced endotoxin-mediated mitochondrial reactive oxygen species and protected the mitochondrial membrane potential. Miltefosine treatment induced mitophagy and dampened NLRP3 inflammasome assembly. Collectively, our data shows that Miltefosine induced ABCA1 mediated cholesterol release, induced AMPK phosphorylation and mitophagy, while dampening NLRP3 inflammasome assembly and IL-1β release.
MeSH term(s)	Animals ; Autophagy/drug effects ; Cell Line ; Cholesterol/metabolism ; HEK293 Cells ; Humans ; Inflammasomes/drug effects ; Inflammasomes/metabolism ; Interleukin-1beta/metabolism ; Macrophages/drug effects ; Macrophages/metabolism ; Mice ; Mitochondria/drug effects ; Mitochondria/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Phosphorylation/drug effects ; Phosphorylcholine/analogs & derivatives ; Phosphorylcholine/pharmacology ; RAW 264.7 Cells ; Reactive Oxygen Species/metabolism ; Signal Transduction/drug effects
Chemical Substances	IL1B protein, human ; Inflammasomes ; Interleukin-1beta ; NLR Family, Pyrin Domain-Containing 3 Protein ; NLRP3 protein, human ; Reactive Oxygen Species ; Phosphorylcholine (107-73-3) ; miltefosine (53EY29W7EC) ; Cholesterol (97C5T2UQ7J)
Language	English
Publishing date	2019-07-31
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-47610-w
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

To top

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito