## 4 Health Benefits of Blackcurrant Anthocyanins and Related Molecular Mechanisms
### Cardioprotective Effect  
BCA was reported effective at maintaining or improving cardiovascular health. A single dose of BCA along with smoking was shown to attenuate the acute endothelial dysfunction induced by smoking and improve the peripheral temperature in young smokers [81]. Short-term BCA intake mitigated central arterial stiffness and central blood pressure in senior subjects [82]. A seven day intake of BCA displayed dose-dependent changes on certain cardiovascular parameters, such as increased cardiac output, increased stroke volume, and decreased total peripheral resistance during supine rest in endurance-trained male cyclists [83]. Six months of BCA consumption also improved the endothelial function in healthy subjects with habitually low fruit and vegetable intake [84].  
The underlying pathology for cardiovascular diseases (CVD) is atherosclerosis. This pathology is complex and involves the structural elements of the arterial wall, circulating cells, and some inflammatory cells [85]. Given the complex pathology of atherosclerosis, the cardioprotective effect of BCA also involves a panel of action mechanisms.  
Two major initiations involved in the development of CVD are the production of reactive oxidation species (ROS) via vessels and lipid oxidation [86]. Excessive ROS may promote endothelial dysfunction, a contributing factor to atherosclerosis. The molecular mechanisms of BCA combatting excessive ROS are discussed in this review. On the other hand, the oxidation of low-density lipoprotein (LDL) in the vessel wall induced an inflammatory cascade that activates many atherogenic pathways, which led to the formation of foam cells [86]. The accumulation of foam cells results in the formation of a fatty streak, which is the earliest visible atherosclerotic lesion. The anti-inflammatory activity of BCA and related molecular mechanisms was covered in other parts of this review.  
Atherosclerotic lesions are initiated through elevated LDL uptake by monocytes and macrophages. The reduction of LDL reduces the risks of CVD [87]. Consumption of anthocyanins from bilberries and blackcurrants decreased LDL-cholesterol levels in dyslipidemia subjects and subjects with metabolic syndrome [88; 89]. One of the therapeutic goals to lower circulating LDL-cholesterol is to induce LDL receptor (LDLR) expression and activity in the liver. BCA increased protein levels of LDLR in Caco-2 cells, which led to the enhanced transport of LDL-cholesterol to the apical side of the enterocytes [90]. The BCA-induced increased hepatic LDLR protein expression was also reported in mice fed a high fat and high cholesterol diet [91].  
Nitric oxide (NO) is a key cellular messenger in the cardiovascular system [92]. NO maintains vascular integrity through inhibiting platelet aggregation, leukocyte-endothelium adhesion, and proliferation of vascular smooth muscle. Diminished NO bioavailability was shown to cause endothelial dysfunction and increased susceptibility to atherosclerosis [93]. NO is generated by three isoforms of nitric oxide synthases (NOS): neuronal, inducible, and endothelial NOS. BCA activated endothelial NOS in vitro in human endothelial cells and in vivo in blood vessel endothelial cells acquired from OVX rats [94; 95]. BCA-treated endothelial cells also showed higher NO levels [95].  
Considering the crucial role of inflammation in the pathogenesis of atherosclerosis, the anti-inflammatory activity of BCA also provided a cardioprotective effect.  
The cardiovascular effect of BCA was not observed in hyperlipidemic rabbits [96].