Abstract
The miR-143/145 cluster regulates VSMC specific gene expression, thus controlling differentiation, plasticity and contractile function, and promoting the VSMC phenotypic switch from a contractile/non-proliferative to a migrating/proliferative state. More recently increased miR-145 expression was observed in human carotid atherosclerotic plaques from symptomatic patients. The goal of this study was to investigate the contribution of miR-143/145 during atherogenesis by generating mice lacking miR-143/145 on an Ldlr-deficient background. Ldlr-/- and Ldlr-/--miR-143/145-/- (DKO) were fed a Western diet (WD) for 16 weeks. At the end of the treatment, the lipid profile and the atherosclerotic lesions were assessed in both groups of mice. Absence of miR-143/145 significantly reduced atherosclerotic plaque size and macrophage infiltration. Plasma total cholesterol levels were lower in DKO and FLPC analysis showed decreased cholesterol content in VLDL and LDL fractions. Interestingly miR-143/145 deficiency per se resulted in increased hepatic and vascular ABCA1 expression. We further confirmed the direct regulation of miR-145 on ABCA1 expression by qRT-PCR, Western blotting and 3’UTR-luciferase reporter assays. In summary, miR-143/145 deficiency significantly reduces atherosclerosis in mice. Therapeutic inhibition of miR-145 might be useful for treating atherosclerotic vascular disease.
| Original language | English |
|---|---|
| Pages (from-to) | 796-802 |
| Number of pages | 7 |
| Journal | Thrombosis and Haemostasis |
| Volume | 112 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2014 |
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Keywords
- ABCA1
- Atherosclerosis
- MiR-143/145
- Smooth muscle cells
ASJC Scopus subject areas
- Hematology
- Medicine(all)
Cite this
MiR-143/145 deficiency attenuates the progression of atherosclerosis in Ldlr-/- mice. / Sala, Federica; Aranda, Juan F.; Rotllan, Noemi; Ramírez, Cristina M.; Aryal, Binod; Elia, Leonardo; Condorelli, Gianluigi; Catapano, Alberico Luigi; Fernández-Hernando, Carlos; Norata, Giuseppe Danilo.
In: Thrombosis and Haemostasis, Vol. 112, No. 4, 2014, p. 796-802.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - MiR-143/145 deficiency attenuates the progression of atherosclerosis in Ldlr-/- mice
AU - Sala, Federica
AU - Aranda, Juan F.
AU - Rotllan, Noemi
AU - Ramírez, Cristina M.
AU - Aryal, Binod
AU - Elia, Leonardo
AU - Condorelli, Gianluigi
AU - Catapano, Alberico Luigi
AU - Fernández-Hernando, Carlos
AU - Norata, Giuseppe Danilo
PY - 2014
Y1 - 2014
N2 - The miR-143/145 cluster regulates VSMC specific gene expression, thus controlling differentiation, plasticity and contractile function, and promoting the VSMC phenotypic switch from a contractile/non-proliferative to a migrating/proliferative state. More recently increased miR-145 expression was observed in human carotid atherosclerotic plaques from symptomatic patients. The goal of this study was to investigate the contribution of miR-143/145 during atherogenesis by generating mice lacking miR-143/145 on an Ldlr-deficient background. Ldlr-/- and Ldlr-/--miR-143/145-/- (DKO) were fed a Western diet (WD) for 16 weeks. At the end of the treatment, the lipid profile and the atherosclerotic lesions were assessed in both groups of mice. Absence of miR-143/145 significantly reduced atherosclerotic plaque size and macrophage infiltration. Plasma total cholesterol levels were lower in DKO and FLPC analysis showed decreased cholesterol content in VLDL and LDL fractions. Interestingly miR-143/145 deficiency per se resulted in increased hepatic and vascular ABCA1 expression. We further confirmed the direct regulation of miR-145 on ABCA1 expression by qRT-PCR, Western blotting and 3’UTR-luciferase reporter assays. In summary, miR-143/145 deficiency significantly reduces atherosclerosis in mice. Therapeutic inhibition of miR-145 might be useful for treating atherosclerotic vascular disease.
AB - The miR-143/145 cluster regulates VSMC specific gene expression, thus controlling differentiation, plasticity and contractile function, and promoting the VSMC phenotypic switch from a contractile/non-proliferative to a migrating/proliferative state. More recently increased miR-145 expression was observed in human carotid atherosclerotic plaques from symptomatic patients. The goal of this study was to investigate the contribution of miR-143/145 during atherogenesis by generating mice lacking miR-143/145 on an Ldlr-deficient background. Ldlr-/- and Ldlr-/--miR-143/145-/- (DKO) were fed a Western diet (WD) for 16 weeks. At the end of the treatment, the lipid profile and the atherosclerotic lesions were assessed in both groups of mice. Absence of miR-143/145 significantly reduced atherosclerotic plaque size and macrophage infiltration. Plasma total cholesterol levels were lower in DKO and FLPC analysis showed decreased cholesterol content in VLDL and LDL fractions. Interestingly miR-143/145 deficiency per se resulted in increased hepatic and vascular ABCA1 expression. We further confirmed the direct regulation of miR-145 on ABCA1 expression by qRT-PCR, Western blotting and 3’UTR-luciferase reporter assays. In summary, miR-143/145 deficiency significantly reduces atherosclerosis in mice. Therapeutic inhibition of miR-145 might be useful for treating atherosclerotic vascular disease.
KW - ABCA1
KW - Atherosclerosis
KW - MiR-143/145
KW - Smooth muscle cells
UR - http://www.scopus.com/inward/record.url?scp=84908519519&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84908519519&partnerID=8YFLogxK
U2 - 10.1160/TH13-11-0905
DO - 10.1160/TH13-11-0905
M3 - Article
C2 - 25008143
AN - SCOPUS:84908519519
VL - 112
SP - 796
EP - 802
JO - Thrombosis and Haemostasis
JF - Thrombosis and Haemostasis
SN - 0340-6245
IS - 4
ER -