# _Vaccinium_ Species (Ericaceae): From Chemical Composition to Bio-Functional Activities
## 5 Biological Properties of _Vaccinium_ Species
### Vaccinium and Atherosclerosis  
Atherosclerosis is one of the major causes of cardiovascular diseases and is characterized by the accumulation of lipids and fibrous plaques in the large arteries, which may lead to heart attacks, strokes, and peripheral vascular diseases [115].  
[PERSON] et al. [116] tested a dried hydroalcoholic extract of _V. myrtillus_ leaves showing a lipid-lowering activity with decrease of 39% of the triglycerides in the blood of dyslipidemic animals. Similarly, _V. corymbosum_ berries decreased blood cholesterol levels, thus reducing cardiovascular risk and promoting atherosclerosis prevention [117; 118]. In addition, consumption of cranberry anthocyanins improved lipid profiles, increasing HDL and decreasing LDL in rats, hamsters fed a high-fat diet and hypercholesterolemic swine [119; 120; 121]. [PERSON] et al. [122] showed that blueberries induce a regression of atherosclerotic plaques in arteries. In this manuscript, the apolipoprotein-E deficient (apoE\(-\)/\(-\)) mice were fed either a control diet or an enriched diet supplemented with 1% freeze-dried wild blueberries for 20 weeks. The plaques, measured at two sites, were 39 and 58% smaller in the mice fed blueberries compared to those fed the control diet, and these effects were associated with the reduction in biomarkers of lipid peroxidation in the liver, such as F2-isoprostane [122]. Similarly, [PERSON] et al. [123] showed that in ApoE\(-\)/\(-\) mice fed either a low-fat diet or high-fat diet, with or without lingonberries, the size of the atherosclerotic plaques, the total, HDL and LDL-VLDL blood cholesterol, and triglycerides, as well as the hepatic gene expression of bile acid synthesis genes (cholesterol 7 \(\alpha\)-hydroxylase (Cyp7a1), sterol 12\(\alpha\)-hydroxylase (Cyp8b1)) were reduced.  
Although published animal studies primarily focused on the specific cardiovascular disease risk factors or biomarkers, and the antioxidant and anti-inflammatory effects, of _Vaccinium_ and its derivatives, clinical data have also been published [10]. Indeed, good results were also observed with cranberry juice in obese men, and hyper-triglyceridemic or diabetic patients [24].  
The molecular mechanisms of atheoprotective effects of _Vaccinium_ are not completely understood and are often associated with antioxidant and anti-inflammatory activities. In fact, the protective activity in atherosclerosis development have been associated with the reduction in oxidative stress, inhibition of inflammation, and regulation of cholesterol accumulation and trafficking [10].  
In apoE\(-\)/\(-\) mice, the treatment with 1% wild blueberries for 20 weeks modulated gene expression and protein levels of scavenger receptors CD36 and SR-A, the principal receptors responsible for the binding and uptake of modified LDL in macrophages [124].  
CD36 and SR-A were found to be lower in peritoneal macrophages of blueberry-fed mice, and fewer ox-LDL-induced foam cells were formed, probably through a mechanism involving PPARy [124]. In addition, [PERSON] et al. [125] demonstrated that blueberry consumption increased the levels of the cholesterol transporter ABCA1, indicating that blueberries may facilitate cholesterol efflux and lowering cholesterol accumulation. Overall, it has been shown that blueberry consumption increased PPAR\(\alpha\), PPAR\(\gamma\), ABCA1 and fatty acid synthase expression, while reducing SREBP-1 levels [10].  
Although several sources of experimental evidence support the atheoprotective effects of _Vaccinium_, further and more in-depth studies are needed to completely elucidate the molecular mechanisms underlying this activity.