Plaque stabilizing effects of apolipoprotein A-IV

F.R.B. Geronimo, P.J. Barter, K.A. Rye, A.K. Heather, Kate Shearston, K.J. Rodgers

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

© 2016. 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.
Original languageEnglish
Pages (from-to)39-46
JournalAtherosclerosis
Volume251
DOIs
Publication statusPublished - 2016

Fingerprint

Apolipoproteins A
Apolipoprotein A-I
Matrix Metalloproteinases
High Fat Diet
Lipids
Messenger RNA
Vascular Cell Adhesion Molecule-1
Apolipoproteins
In Situ Nick-End Labeling
Apolipoproteins E
Inbred C57BL Mouse
Knockout Mice
apolipoprotein A-IV
Proteins
Collagen
Arteries
Macrophages
Apoptosis
Phenotype
Injections

Cite this

Geronimo, F. R. B., Barter, P. J., Rye, K. A., Heather, A. K., Shearston, K., & Rodgers, K. J. (2016). Plaque stabilizing effects of apolipoprotein A-IV. Atherosclerosis, 251, 39-46. https://doi.org/10.1016/j.atherosclerosis.2016.04.019
Geronimo, F.R.B. ; Barter, P.J. ; Rye, K.A. ; Heather, A.K. ; Shearston, Kate ; Rodgers, K.J. / Plaque stabilizing effects of apolipoprotein A-IV. In: Atherosclerosis. 2016 ; Vol. 251. pp. 39-46.
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abstract = "{\circledC} 2016. 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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Geronimo, FRB, Barter, PJ, Rye, KA, Heather, AK, Shearston, K & Rodgers, KJ 2016, 'Plaque stabilizing effects of apolipoprotein A-IV' Atherosclerosis, vol. 251, pp. 39-46. https://doi.org/10.1016/j.atherosclerosis.2016.04.019

Plaque stabilizing effects of apolipoprotein A-IV. / Geronimo, F.R.B.; Barter, P.J.; Rye, K.A.; Heather, A.K.; Shearston, Kate; Rodgers, K.J.

In: Atherosclerosis, Vol. 251, 2016, p. 39-46.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Plaque stabilizing effects of apolipoprotein A-IV

AU - Geronimo, F.R.B.

AU - Barter, P.J.

AU - Rye, K.A.

AU - Heather, A.K.

AU - Shearston, Kate

AU - Rodgers, K.J.

PY - 2016

Y1 - 2016

N2 - © 2016. 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.

AB - © 2016. 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.

U2 - 10.1016/j.atherosclerosis.2016.04.019

DO - 10.1016/j.atherosclerosis.2016.04.019

M3 - Article

VL - 251

SP - 39

EP - 46

JO - Atherosclerosis

JF - Atherosclerosis

SN - 0021-9150

ER -