Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 39-46 |
| Journal | Atherosclerosis |
| Volume | 251 |
| DOIs | |
| Publication status | Published - 2016 |
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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 journal › Article
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 -