# Legumes as Functional Food for Cardiovascular Disease
## 3 Legumes as Functional Food for Cardiovascular Diseases
### Soybean (Glycine Max L.)  
#### 3.1.1 Benefits of Soybeans Relating to Cardiovascular Health  
Soybean (_Glycine max_ L.) is one of the most abundant plant sources constituting 36-56% protein [129]. Soybean proteins are categorized as complete proteins for human health and growth since they are highly digestible, supply all of the essential amino acids, and have a Protein Digestibility Corrected Amino Acid Score (PDCAAS) score of 1.0 which is comparable to casein and egg protein. These soybean proteins, though, are low in methionine:glycine and lysine:arginine ratios compared to casein [129]. Soybean proteins are ascribed to reduce cholesterol levels, control lipid metabolism and fatty acid oxidation, improve glucose homeostasis, are anti-hypertensive and anti-oxidative, and have the ability to control hunger and obesity [112; 113; 129; 135; 146; 195; 136; 137; 138; 139; 140; 135; 139; 141; 142; 143; 144; 145; 1  
humans, soybean peptides stimulated fecal steroid excretion that led to lower serum TC levels [118,119]. Soybean proteins also decreased plasma and hepatic TAGs due to the reduced transcription and translation of the hepatic sterol regulatory element binding protein (SREBP)-1 either through an insulin-dependent or -independent pathway [100,148,204,205,206,207,208,209,200,201,202,203,204,205,206,207]. These SREBPs are basic helix-loop-helix leucine zipper (bHLH-leu) and membrane-bound transcription factors that activate about 30 genes involved in fatty acid and cholesterol biosynthesis [158,159,208,209,210]. There are three SREBP isoforms, SREBP-1 (1a and 1c), which activate fatty acid synthesis and result from the altered transcription splicing of the SREBP-gene, and SREBP-2, which activate genes in the cholesterol pathway. These SREBPs are further regulated through autophagy and by the PI3K-mTORC1-AKT pathway through an unknown mechanism [158,208]. These SREBPs undergo a two-step proteolytic cleavage in the Golgi apparatus to release their N-terminal fragment that still contains the bHLH-leu motif. This N-terminal fragment enters the nucleus and binds to steroid response elements (SREs) found in a number of genes involved in cholesterol biosynthesis such as squalene synthase and HMG-CoA reductase [158,208]. Aside from the bHLH-leu motif, these SREBPs also contain an internal intronic region that produces miR-33 that reduces translation of other fatty acid oxidation genes including ATP binding cassette subfamily A member 1 (\(ABCA1\)) and ATP-binding cassette sub-family G member 1-like (\(ABCG\)). This miR-33 activity control fatty acid oxidation genes and is complementary to the activity of the SREBP-N-terminal domain found in SREBP-1a, -1c, and -2 described herein [208]. Via the insulin-dependent pathway, soybean proteins decrease insulin, thereby, reducing SREBP-1 expression in the liver and in rat primary hepatocytes [103], and increase the removal of hepatic insulin [204]. Through the insulin-independent pathway, soy proteins reduce SREBP-1 expression through the negative regulation of liver X receptor (LXR) mRNA expression [206] In either case, the reduction of SREBP-1 by the soybean proteins reduces the mRNA of various hepatic lipogenic enzymes such as glucose-6-phosphate dehydrogenase (G6 PDH), malate enzyme, FASN, acetyl-CoA carboxylase alpha, and beta (ACC\(\alpha\) and ACC\(\beta\)) and ATPase/ATP synthase reducing the biosynthesis of endogenous fatty acids [100,126,149,205,206,211,212,213,214]. Soybean proteins were found to reduce malate enzyme and fatty acid synthetase gene expression in rats [100,205,213]. ACC regulation mediated by soybean proteins is through the thyroid-receptor (TR)-dependent pathway, whereby thyroid hormones regulate the binding to the thyroid hormone receptor response elements found on the ACC promoter. Through the SREBP-dependent pathway, soybean protein isolates inhibit the binding of SREBP-1 to one of the two promoters controlling ACC-alpha gene expression [103,215,216].