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RNA interference of myocyte enhancer factor 2A accelerates atherosclerosis in apolipoprotein E-deficient mice.

Zhou WP, Zhang H, Zhao YX, Liu GQ, Zhang JY - PLoS ONE (2015)

Bottom Line: Myocyte enhancer factor-2A (MEF 2A) has been shown to be involved in atherosclerotic lesion development, but its role in preexisting lesions is still unclear.Six weeks after surgery, lentiviral shRNA construct was used to silence the expression of MEF 2A.The expression level of MEF 2A was significantly reduced in plasma and plaque in the RNAi group, compared to the control and NC groups, whereas the expression level of pro-inflammatory cytokines was markedly increased.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China.

ABSTRACT

Objective: Myocyte enhancer factor-2A (MEF 2A) has been shown to be involved in atherosclerotic lesion development, but its role in preexisting lesions is still unclear. In the present study we aim to assess the role of MEF 2A in the progression of pre-existing atherosclerosis.

Methods: Eighty apolipoprotein E-deficient mice (APOE KO) were randomly allocated to control, scramble and MEF 2A RNA interference (RNAi) groups, and constrictive collars were used to induce plaque formation. Six weeks after surgery, lentiviral shRNA construct was used to silence the expression of MEF 2A. Carotid plaques were harvested for analysis 4 weeks after viral vector transduction. Inflammatory gene expression in the plasma and carotid plaques was determined by using ELISAs and real-time RT-PCR.

Results: The expression level of MEF 2A was significantly reduced in plasma and plaque in the RNAi group, compared to the control and NC groups, whereas the expression level of pro-inflammatory cytokines was markedly increased. Silencing MEF 2A using lentiviral shRNA significantly reduced the plaque collagen content and fibrous cap thickness, as well as increased plaque area. However, silencing MEF 2A had no obvious effect on plaque lipid content.

Conclusions: Lentivirus-mediated MEF 2A shRNA accelerates inflammation and atherosclerosis in APOE KO mice, but has no effect on lipoprotein levels in plasma.

No MeSH data available.


Related in: MedlinePlus

Knockdown of MEF 2A in vivo.(A) mRNA expression of MEF 2A in the plaques of the control, NC, and MEF 2A shRNA groups at week 10; (B) Protein expression of MEF 2A in the plaques of the control, NC, and shRNA groups; (C) The concentration MEF 2A in the plasma; (D) Representative Western blots used for quantification. Data are presented in the mean ± SD. * P < 0.05
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pone.0121823.g002: Knockdown of MEF 2A in vivo.(A) mRNA expression of MEF 2A in the plaques of the control, NC, and MEF 2A shRNA groups at week 10; (B) Protein expression of MEF 2A in the plaques of the control, NC, and shRNA groups; (C) The concentration MEF 2A in the plasma; (D) Representative Western blots used for quantification. Data are presented in the mean ± SD. * P < 0.05

Mentions: We examined the mRNA and protein expression of MEF 2A in the carotid plaques, as well as the MEF 2A expression in the plasma following lentiviral vector delivery. MEF 2A mRNA and protein expression was statistically reduced in plasma of APO E KO mice in the MEF 2A knockdown group compared to scramble control and NC groups (Fig. 2). MEF 2A mRNA expression was reduced by 68.6% (P < 0.01, Fig. 2A), while the MEF 2A protein was decreased by 60.5% (P < 0.01, Fig. 2B and D) and the plasma concentration of MEF 2A was lowered by 56.4% (P < 0.05, Fig. 2C), compared to those in the scramble control and NC groups. In contrast, the NC group did not differ from the control group in MEF 2A expression.


RNA interference of myocyte enhancer factor 2A accelerates atherosclerosis in apolipoprotein E-deficient mice.

Zhou WP, Zhang H, Zhao YX, Liu GQ, Zhang JY - PLoS ONE (2015)

Knockdown of MEF 2A in vivo.(A) mRNA expression of MEF 2A in the plaques of the control, NC, and MEF 2A shRNA groups at week 10; (B) Protein expression of MEF 2A in the plaques of the control, NC, and shRNA groups; (C) The concentration MEF 2A in the plasma; (D) Representative Western blots used for quantification. Data are presented in the mean ± SD. * P < 0.05
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4368513&req=5

pone.0121823.g002: Knockdown of MEF 2A in vivo.(A) mRNA expression of MEF 2A in the plaques of the control, NC, and MEF 2A shRNA groups at week 10; (B) Protein expression of MEF 2A in the plaques of the control, NC, and shRNA groups; (C) The concentration MEF 2A in the plasma; (D) Representative Western blots used for quantification. Data are presented in the mean ± SD. * P < 0.05
Mentions: We examined the mRNA and protein expression of MEF 2A in the carotid plaques, as well as the MEF 2A expression in the plasma following lentiviral vector delivery. MEF 2A mRNA and protein expression was statistically reduced in plasma of APO E KO mice in the MEF 2A knockdown group compared to scramble control and NC groups (Fig. 2). MEF 2A mRNA expression was reduced by 68.6% (P < 0.01, Fig. 2A), while the MEF 2A protein was decreased by 60.5% (P < 0.01, Fig. 2B and D) and the plasma concentration of MEF 2A was lowered by 56.4% (P < 0.05, Fig. 2C), compared to those in the scramble control and NC groups. In contrast, the NC group did not differ from the control group in MEF 2A expression.

Bottom Line: Myocyte enhancer factor-2A (MEF 2A) has been shown to be involved in atherosclerotic lesion development, but its role in preexisting lesions is still unclear.Six weeks after surgery, lentiviral shRNA construct was used to silence the expression of MEF 2A.The expression level of MEF 2A was significantly reduced in plasma and plaque in the RNAi group, compared to the control and NC groups, whereas the expression level of pro-inflammatory cytokines was markedly increased.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China.

ABSTRACT

Objective: Myocyte enhancer factor-2A (MEF 2A) has been shown to be involved in atherosclerotic lesion development, but its role in preexisting lesions is still unclear. In the present study we aim to assess the role of MEF 2A in the progression of pre-existing atherosclerosis.

Methods: Eighty apolipoprotein E-deficient mice (APOE KO) were randomly allocated to control, scramble and MEF 2A RNA interference (RNAi) groups, and constrictive collars were used to induce plaque formation. Six weeks after surgery, lentiviral shRNA construct was used to silence the expression of MEF 2A. Carotid plaques were harvested for analysis 4 weeks after viral vector transduction. Inflammatory gene expression in the plasma and carotid plaques was determined by using ELISAs and real-time RT-PCR.

Results: The expression level of MEF 2A was significantly reduced in plasma and plaque in the RNAi group, compared to the control and NC groups, whereas the expression level of pro-inflammatory cytokines was markedly increased. Silencing MEF 2A using lentiviral shRNA significantly reduced the plaque collagen content and fibrous cap thickness, as well as increased plaque area. However, silencing MEF 2A had no obvious effect on plaque lipid content.

Conclusions: Lentivirus-mediated MEF 2A shRNA accelerates inflammation and atherosclerosis in APOE KO mice, but has no effect on lipoprotein levels in plasma.

No MeSH data available.


Related in: MedlinePlus