Inhibition of 14q32 microRNA miR-495 reduces lesion formation, intimal hyperplasia and plasma cholesterol levels in experimental restenosis
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Inhibition of 14q32 microRNA miR-495 reduces lesion formation, intimal hyperplasia and plasma cholesterol levels in experimental restenosis. / Welten, Sabine M.J.; de Jong, Rob C.M.; Wezel, Anouk; de Vries, Margreet R.; Boonstra, Martin C.; Parma, Laura; Jukema, J. Wouter; van der Sluis, Tetje C.; Arens, Ramon; Bot, Ilze; Agrawal, Sudhir; Quax, Paul H.A.; Nossent, A. Yaël.
In: Atherosclerosis, Vol. 261, 01.06.2017, p. 26-36.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Inhibition of 14q32 microRNA miR-495 reduces lesion formation, intimal hyperplasia and plasma cholesterol levels in experimental restenosis
AU - Welten, Sabine M.J.
AU - de Jong, Rob C.M.
AU - Wezel, Anouk
AU - de Vries, Margreet R.
AU - Boonstra, Martin C.
AU - Parma, Laura
AU - Jukema, J. Wouter
AU - van der Sluis, Tetje C.
AU - Arens, Ramon
AU - Bot, Ilze
AU - Agrawal, Sudhir
AU - Quax, Paul H.A.
AU - Nossent, A. Yaël
N1 - Publisher Copyright: © 2017 Elsevier B.V.
PY - 2017/6/1
Y1 - 2017/6/1
N2 - Background and aims We aimed at investigating the role of 14q32 microRNAs in intimal hyperplasia and accelerated atherosclerosis; two major contributors to restenosis. Restenosis occurs regularly in patients treated for coronary artery disease and peripheral arterial disease. We have previously shown that inhibition of 14q32 microRNAs leads to increased post-ischemic neovascularization, and microRNA miR-494 also decreased atherosclerosis, while increasing plaque stability. We hypothesized that 14q32 microRNA inhibition has beneficial effects on intimal hyperplasia, as well as accelerated atherosclerosis. Methods Non-constrictive cuffs were placed around both femoral arteries of C57BL/6J mice to induce intimal hyperplasia. Accelerated atherosclerotic plaque formation was induced in hypercholesterolemic ApoE−/− mice by placing semi-constrictive collars around both carotid arteries. 14q32 microRNAs miR-329, miR-494 and miR-495 were inhibited in vivo using Gene Silencing Oligonucleotides (GSOs). Results GSO-495 administration led to a 32% reduction of intimal hyperplasia. Moreover, the number of macrophages in the arterial wall of mice treated with GSO-495 was reduced by 55%. Inhibition of miR-329 and miR-494 had less profound effects on intimal hyperplasia. GSO-495 administration also decreased atherosclerotic plaque formation by 52% and plaques of GSO-495 treated animals showed a more stable phenotype. Finally, cholesterol levels were also decreased in GSO-495 treated animals, via reduction of the VLDL-fraction. Conclusions GSO-495 administration decreased our primary outcomes, namely intimal hyperplasia, and accelerated atherosclerosis. GSO-495 administration also favourably affected multiple secondary outcomes, including macrophage influx, plaque stability and total plasma cholesterol levels. We conclude that 14q32 microRNA miR-495 is a promising target for prevention of restenosis.
AB - Background and aims We aimed at investigating the role of 14q32 microRNAs in intimal hyperplasia and accelerated atherosclerosis; two major contributors to restenosis. Restenosis occurs regularly in patients treated for coronary artery disease and peripheral arterial disease. We have previously shown that inhibition of 14q32 microRNAs leads to increased post-ischemic neovascularization, and microRNA miR-494 also decreased atherosclerosis, while increasing plaque stability. We hypothesized that 14q32 microRNA inhibition has beneficial effects on intimal hyperplasia, as well as accelerated atherosclerosis. Methods Non-constrictive cuffs were placed around both femoral arteries of C57BL/6J mice to induce intimal hyperplasia. Accelerated atherosclerotic plaque formation was induced in hypercholesterolemic ApoE−/− mice by placing semi-constrictive collars around both carotid arteries. 14q32 microRNAs miR-329, miR-494 and miR-495 were inhibited in vivo using Gene Silencing Oligonucleotides (GSOs). Results GSO-495 administration led to a 32% reduction of intimal hyperplasia. Moreover, the number of macrophages in the arterial wall of mice treated with GSO-495 was reduced by 55%. Inhibition of miR-329 and miR-494 had less profound effects on intimal hyperplasia. GSO-495 administration also decreased atherosclerotic plaque formation by 52% and plaques of GSO-495 treated animals showed a more stable phenotype. Finally, cholesterol levels were also decreased in GSO-495 treated animals, via reduction of the VLDL-fraction. Conclusions GSO-495 administration decreased our primary outcomes, namely intimal hyperplasia, and accelerated atherosclerosis. GSO-495 administration also favourably affected multiple secondary outcomes, including macrophage influx, plaque stability and total plasma cholesterol levels. We conclude that 14q32 microRNA miR-495 is a promising target for prevention of restenosis.
KW - 14q32
KW - Accelerated atherosclerosis
KW - microRNA
KW - Restenosis
UR - http://www.scopus.com/inward/record.url?scp=85018477788&partnerID=8YFLogxK
U2 - 10.1016/j.atherosclerosis.2017.04.011
DO - 10.1016/j.atherosclerosis.2017.04.011
M3 - Journal article
C2 - 28445809
AN - SCOPUS:85018477788
VL - 261
SP - 26
EP - 36
JO - Journal of atherosclerosis research
JF - Journal of atherosclerosis research
SN - 1567-5688
ER -
ID: 395077643