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Published on: September 26, 2018
Catechin reduces atherosclerotic lesion development in apo E-deficient mice: a transcriptomic study
Sylvain Auclair1, Dragan Milenkovic, Catherine Besson
1Unité de Nutrition Humaine UMR1019, INRA-Clermont Ferrand/Theix, 63122 Saint Genès Champanelle, France.
Abstract:
Much experimental evidence supports a protective role of dietary flavonoids against cardiovascular diseases. The aim of the present study was to investigate the anti-atherosclerotic effects of catechin supplemented in the diet of apoE deficient mice at a low nutritional level and to explore the mechanisms of action by a transcriptomic approach. After 6 weeks of supplementation, atherosclerotic lesions were assessed by histomorphometry and several markers of lipid, inflammation and oxidative stress status were evaluated. Analysis of the global gene expression in the aorta was carried out using pangenomic arrays. Catechin supplementation reduced the mean atherosclerotic lesion area by 32% but had no effect on total cholesterol and triacylglycerol levels in the plasma and the liver. The plasma antioxidant capacity (FRAP) and inflammatory status (serum amyloid A) were unchanged. The expression of 450 genes was significantly modified by catechin supplementation. Some of the most significantly down-regulated genes included genes coding for adhesion molecules such as CD34 and PSGL-1 known to play a key role in leukocyte adhesion to the endothelium. Other genes involved in energy metabolism, lipid metabolism and lipids trafficking such as FABP4, LPL and SCARA5 were down-regulated and may contribute to the atheroprotective effect of catechin. This work shows that transcriptomic allows characterizing the biological effects of low doses of flavonoids where common markers were not significantly affected.
Insights
Dietary catechin supplementation reduced atherosclerotic lesion size in mice by 32%. This study utilized transcriptomics to reveal underlying mechanisms, identifying altered gene expression in lipid metabolism and adhesion molecules, offering new insights into flavonoid
Area of Science:
- Cardiovascular Research
- Nutritional Science
- Molecular Biology
Background:
- Dietary flavonoids, including catechin, are linked to cardiovascular protection.
- Atherosclerosis is a major cardiovascular disease driven by lipid accumulation and inflammation.
- Understanding the molecular mechanisms of flavonoid action is crucial for therapeutic development.
Purpose of the Study:
- To investigate the anti-atherosclerotic effects of dietary catechin in apolipoprotein E-deficient (apoE-/-) mice.
- To explore the molecular mechanisms of catechin's action using a transcriptomic approach.
- To assess catechin's impact on lesion development and related molecular pathways at a low nutritional level.
Main Methods:
- Supplementation of apoE-/- mice with catechin for 6 weeks.
- Assessment of atherosclerotic lesions via histomorphometry.
- Evaluation of plasma and liver lipid profiles, antioxidant capacity (FRAP), and inflammatory markers (serum amyloid A).
- Global gene expression analysis of aortic tissue using pangenomic arrays.
Main Results:
- Catechin supplementation significantly reduced atherosclerotic lesion area by 32%.
- No significant changes were observed in plasma or liver total cholesterol and triacylglycerol levels.
- Plasma antioxidant capacity and inflammatory status remained unchanged.
- Transcriptomic analysis revealed significant alterations in 450 genes, including down-regulation of adhesion molecules (e.g., CD34, PSGL-1) and genes involved in lipid metabolism (e.g., FABP4, LPL, SCARA5).
Conclusions:
- Dietary catechin exhibits anti-atherosclerotic effects in apoE-/- mice, even at low doses.
- Transcriptomic analysis provides a deeper understanding of catechin's mechanisms, highlighting its impact on gene expression related to leukocyte adhesion and lipid metabolism.
- This study demonstrates the utility of transcriptomics in identifying biological effects of low-dose flavonoids when traditional markers show no significant changes.
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