# Legumes as Functional Food for Cardiovascular Disease
## 3 Legumes as Functional Food for Cardiovascular Diseases
### Lupin (Lupinus spp.) Lupin is a generic term for proteins derived from four domesticated _Lupinus_ species-_Lupinus_ (white lupin), _L. luteus_ (yellow lupin), _L. mutabilis_ (blue lupin) and _L. angusfolius_ (narrow-leaf lupin) [153; 287]. These are mostly produced in Australia, France, Poland, Russia, Hungary, and Italy [153]. These are excellent legumes since their protein content is comparable to soybean and is a good source of minerals, unsaturated fatty acids, vitamins, and tocopherols while having negligible amounts of phytoestrogens such as isoflav and other antinutrients [153; 288; 289; 290; 281; 282; 283; 284; 285; 286; 287; 288; 289; 291; 292]. Lupin and its protein isolates were found to decrease cholesterol levels in various model animal systems such as rats, hamsters, pigs, and humans [152; 153; 157; 160; 290; 293]. Lupin proteins are ascribed in lowering plasma TC and LDL-C in rats fed with a high-fat diet [153] and the significant improvement of LDL:HDL-C ratios in humans [160]. Male Sprague Dawley rats fed with 50 mg/rat of the lupin total protein extract for two weeks showed significant reduction in TAGs by 16% (_p_ < 0.01), TC by 21%, and VLDL-LDL-C by 30% (_p_ < 0.001) while increasing HDL-C by 20% (_p_ < 0.10) compared to the vehicle-fed rats [152]. Pregnant female rats fed with 200 g/kg lupin proteins during pregnancy until the post-lactation stage showed decreased levels of plasma TAG (by 55%), plasma TC, VLDL, LDL, and hepatic cholesterol compared to dams fed with a casein-rich diet. Such lupin protein-fed rats also exhibited higher TAG and LDL receptors levels in their liver by more than twofold and in their milk by 81% and were found to have significantly (_p_ < 0.05) upregulated lipogenic genes in their mammary glands [290]. In human trials, lupin protein isolates (25 g per day) significantly lowered blood pressure (_p_ < 0.044), LDL-C levels (_p_ < 0.036), and LDL:HDL-C ratios (_p_ = 0.003) after four weeks compared to individuals who consumed a milk protein isolate or a casein diet [157; 160]. According to the [PERSON] et al., (2010), the significant reduction in plasma TC due to the ingestion of the lupin proteins was mainly due to the decrease HDL-C levels, independent of LDL-C changes, leading to lower cardiovascular risk [160]. [PERSON] et al., (2004) [153] demonstrated significant reduction of VLDL and LDL in rats fed with high-cholesterol and cholic acid that were supplemented with lupin protein isolates (50 mg/day). In a leporine model, [PERSON] et al., (2008) [155] detected significantly lower cholesterol levels after 60 days by 40% and after 90 days by 33% (_p_ < 0.05) and a significant reduction in focal lesion progression by 37% (_p_ < 0.05) after feeding such animals with lupin proteins compared to the casein-fed group. Lupin proteins were found to downregulate the SREBP-1 transcription factor in rat livers resulting in decreased fatty acid synthesis [153; 154; 294] and upregulated LDL receptors in human hepatoma cells [153; 290; 294]. Lupin proteins also significantly reduced the inflammation-associated C-reactive protein (CPT) biomarker that is linked to the risk of cardiovascular events [157; 295; 296]. _Lupinus albus_ and _L. angustifolius_ were shown to improve the lipoprotein profile and lower blood pressure in rat models [153; 156; 157; 290; 297; 298]. In in vitro studies using HepG2 cell lines, [PERSON] et al., (2014) [299] discovered that pepsin and trypsin-digested _L. albus_ proteins induced the LDL receptor protein resulting in the subsequent LDL uptake and stimulated the AKT-GSK signaling pathway suggesting that the AKT-GSK is involved in the upregulation of the LDL-receptor-SREBP2 pathway. Interestingly, [PERSON] et al., (2012) determined that black soybean (_Glycine max_ L.) peptides also stimulated the same AKT-GSK signaling pathway via the phosphorylation of GSK and FoxO1 in HepG2 cells [106].