Plaque stabilizing effects of apolipoprotein A-IV.

Geronimo, FRB; Barter, PJ; Rye, KA; Heather, AK; Shearston, KD; Rodgers, KJ

Plaque stabilizing effects of apolipoprotein A-IV.

Geronimo, FRB Barter, PJ Rye, KA Heather, AK Shearston, KD Rodgers, KJ

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Publisher:: ELSEVIER IRELAND LTD
Publication Type:: Journal Article
Citation:: Atherosclerosis, 2016, 251, pp. 39-46
Issue Date:: 2016-08

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Field	Value	Language
dc.contributor.author	Geronimo, FRB
dc.contributor.author	Barter, PJ
dc.contributor.author	Rye, KA
dc.contributor.author	Heather, AK
dc.contributor.author	Shearston, KD
dc.contributor.author	Rodgers, KJ
dc.date.accessioned	2022-02-11T04:00:48Z
dc.date.available	2016-04-24
dc.date.available	2022-02-11T04:00:48Z
dc.date.issued	2016-08
dc.identifier.citation	Atherosclerosis, 2016, 251, pp. 39-46
dc.identifier.issn	0021-9150
dc.identifier.issn	1879-1484
dc.identifier.uri	http://hdl.handle.net/10453/154401
dc.description.abstract	BACKGROUND AND AIMS: Apolipoprotein (apo) A-IV, the third most abundant HDL-associated protein, is atheroprotective and shares similar properties as apoA-I. We have reported previously that apoA-I, the most abundant apolipoprotein in HDL, inhibits plaque disruption in a mouse model. We aimed at examining the effects of apoA-IV on markers of plaque stability in vivo. METHODS: Plaques within brachiocephalic arteries of 16-week old apoE-knockout C57BL/6 mice were examined for changes in composition after 10 weeks on a high-fat diet (HFD). The animals received twice-weekly injections of human lipid-free apoA-IV (1 mg/kg, n = 31) or PBS (n = 32) during the 9th and 10th weeks of the HFD. RESULTS: In the apoA-IV treated mice, there were significantly fewer hemorrhagic plaque disruptions (9/31 vs. 18/32, p < 0.05), thicker fibrous caps, smaller lipid cores, a lower macrophage:SMC ratio, less MMP-9 protein, more collagen, and fewer proliferating cells. In the plaques of mice given apoA-IV, MCP-1, VCAM-1, and inducible NOS were also significantly lower. Based on the percentage of cleaved PARP-positive and TUNEL-positive plaque nuclei, apoA-IV reduced apoptosis. in HMDMs, apoA-IV reduced MMP-9 mRNA expression by half, doubled mRNA levels of TIMP1 and decreased MMP-9 activity. CONCLUSIONS: ApoA-IV treatment is associated with a more stable plaque phenotype and a reduced incidence of acute disruptions in this mouse model.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	ELSEVIER IRELAND LTD
dc.relation.ispartof	Atherosclerosis
dc.relation.isbasedon	10.1016/j.atherosclerosis.2016.04.019
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	1102 Cardiorespiratory Medicine and Haematology, 1103 Clinical Sciences
dc.subject.classification	Cardiovascular System & Hematology
dc.subject.mesh	Animals
dc.subject.mesh	Apolipoproteins A
dc.subject.mesh	Apoptosis
dc.subject.mesh	Arteries
dc.subject.mesh	Atherosclerosis
dc.subject.mesh	Diet, High-Fat
dc.subject.mesh	Humans
dc.subject.mesh	Inflammation
dc.subject.mesh	Lipoproteins, HDL
dc.subject.mesh	Macrophages
dc.subject.mesh	Male
dc.subject.mesh	Matrix Metalloproteinase 9
dc.subject.mesh	Mice
dc.subject.mesh	Mice, Inbred C57BL
dc.subject.mesh	Mice, Knockout, ApoE
dc.subject.mesh	Oxidative Stress
dc.subject.mesh	Phenotype
dc.subject.mesh	Plaque, Atherosclerotic
dc.subject.mesh	Vascular Cell Adhesion Molecule-1
dc.subject.mesh	Arteries
dc.subject.mesh	Macrophages
dc.subject.mesh	Animals
dc.subject.mesh	Mice, Inbred C57BL
dc.subject.mesh	Humans
dc.subject.mesh	Mice
dc.subject.mesh	Inflammation
dc.subject.mesh	Lipoproteins, HDL
dc.subject.mesh	Apolipoproteins A
dc.subject.mesh	Vascular Cell Adhesion Molecule-1
dc.subject.mesh	Apoptosis
dc.subject.mesh	Oxidative Stress
dc.subject.mesh	Phenotype
dc.subject.mesh	Male
dc.subject.mesh	Atherosclerosis
dc.subject.mesh	Matrix Metalloproteinase 9
dc.subject.mesh	Plaque, Atherosclerotic
dc.subject.mesh	Diet, High-Fat
dc.subject.mesh	Mice, Knockout, ApoE
dc.title	Plaque stabilizing effects of apolipoprotein A-IV.
dc.type	Journal Article
utslib.citation.volume	251
utslib.location.activity	Ireland
utslib.for	1103 Clinical Sciences
utslib.for	1102 Cardiorespiratory Medicine and Haematology
utslib.for	1103 Clinical Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Medical and Molecular Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Centre for Health Technologies (CHT)
utslib.copyright.status	closed_access	*
dc.date.updated	2022-02-11T04:00:46Z
pubs.publication-status	Published
pubs.volume	251

Abstract:

BACKGROUND AND AIMS: Apolipoprotein (apo) A-IV, the third most abundant HDL-associated protein, is atheroprotective and shares similar properties as apoA-I. We have reported previously that apoA-I, the most abundant apolipoprotein in HDL, inhibits plaque disruption in a mouse model. We aimed at examining the effects of apoA-IV on markers of plaque stability in vivo. METHODS: Plaques within brachiocephalic arteries of 16-week old apoE-knockout C57BL/6 mice were examined for changes in composition after 10 weeks on a high-fat diet (HFD). The animals received twice-weekly injections of human lipid-free apoA-IV (1 mg/kg, n = 31) or PBS (n = 32) during the 9th and 10th weeks of the HFD. RESULTS: In the apoA-IV treated mice, there were significantly fewer hemorrhagic plaque disruptions (9/31 vs. 18/32, p < 0.05), thicker fibrous caps, smaller lipid cores, a lower macrophage:SMC ratio, less MMP-9 protein, more collagen, and fewer proliferating cells. In the plaques of mice given apoA-IV, MCP-1, VCAM-1, and inducible NOS were also significantly lower. Based on the percentage of cleaved PARP-positive and TUNEL-positive plaque nuclei, apoA-IV reduced apoptosis. in HMDMs, apoA-IV reduced MMP-9 mRNA expression by half, doubled mRNA levels of TIMP1 and decreased MMP-9 activity. CONCLUSIONS: ApoA-IV treatment is associated with a more stable plaque phenotype and a reduced incidence of acute disruptions in this mouse model.

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http://hdl.handle.net/10453/154401