Key result
CCN3 overexpression cuts LDL-C ~49% and reduces atherosclerotic plaque in mice.
Why the study?
Although CCN3 plays a role in regulating vascular endothelial cell inflammation, its specific role in the inflammation and progression of atherosclerosis remained unclear.
Does adenovirus-mediated overexpression of CCN3 inhibit vascular inflammation, improve dyslipidemia, and reduce plaque progression in an apolipoprotein E-deficient mouse model of atherosclerosis?
Does adenovirus-mediated overexpression of CCN3 inhibit vascular inflammation, improve dyslipidemia, and reduce plaque progression in an apolipoprotein E-deficient mouse model of atherosclerosis?
Answers are grounded in this paper and cite their sources.
Preclinical evidence demonstrates that CCN3 overexpression attenuates vascular inflammation, improves lipid profiles, and stabilizes atherosclerotic plaques in ApoE-deficient mice, identifying CCN3 as a potential therapeutic target for atherosclerosis.
Background Cysteine-rich 61/connective tissue growth factor/nephroblastoma overexpressed (CCN) 3 has been recently reported to play a role in regulating inflammation of vascular endothelial cells. However, the role of CCN3 in atherosclerosis, which is characterized by vascular inflammation, remains unclear. Hypothesis and Objectives Overexpression of CCN3 may relieve the inflammation response in and inhibit the progress of atherosclerosis. We aimed to explore the potential roles of CCN3 in inflammation in atherosclerosis. Strategy and Main Results In in vitro studies using cultured human aortic endothelial cells and human umbilical vein endothelial cells, CCN3 mRNA and protein expression significantly decreased in response to tumor necrosis factor-α and interleukin-1β treatments (p<0.05), when analyzed by quantitative real-time polymerase chain reaction and Western blot. Using a mouse model of atherosclerosis, the mRNA and protein levels of CCN3 decreased by 72.2% (p = 0.041) and 86.4% (p = 0.036), respectively, compared with levels in wild-type control mice, respectively. Overexpression of CCN3 by adenovirus-mediated gene overexpression decreased low-density lipoprotein cholesterol by 48.9% (p = 0.017), total cholesterol by 58.9% (p = 0.031), and triglycerides by 56.8% (p = 0.022), and it increased high-density lipoprotein cholesterol level by 2.16-fold (p = 0.039), compared with control groups. Additionally, a reduced plaque area and increased fibrous cap were observed (p<0.05). Furthermore, CCN3 overexpression decreased cell adhesion molecule-1 mRNA expression by 84.7% (p = 0.007) and intercellular adhesion molecule-1 mRNA expression by 61.2% (p = 0.044). Inflammatory factors, including matrix metalloproteinases, cyclooxygenase 2, and tissue factor also significantly (p<0.05) decreased with CCN3 overexpression in the atherosclerotic mouse model. Additionally, CCN1 and CCN2, which have been reported to be highly expressed in aortic atherosclerotic plaques, were significantly downregulated (p<0.05) by CCN3 overexpression. Conclusion CCN3 overexpression is associated with control of inflammatory processes and reversion of dyslipidemia in the process of atherosclerosis, which implies that CCN3 may be a promising target in the treatment of atherosclerosis.
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Liu et al. (2014) studied Atherosclerosis. Adenovirus-mediated CCN3 gene overexpression vs. Control groups and wild-type control mice was evaluated on Lipid profile, atherosclerotic plaque area, fibrous cap, and inflammatory factor expression (p=<0.05). Adenovirus-mediated CCN3 overexpression in ApoE-deficient mice decreased LDL-C by 48.9% (p=0.017) and total cholesterol by 58.9% (p=0.031) while reducing plaque area and vascular inflammation (p<0.05).
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