# 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 proteins also decrease dephosphorylation of the mitochondrial ATPase/ATP synthase \(\beta\) subunit, thus, increasing the enzyme's activity [214]. The hypocholesterolemic benefit of soybean proteins was also associated with the control of other cholesterol synthesis genes and their translated proteins. Soybean isolates significantly reduced HMG-CoA reductase in rat livers reducing cholesterol biosynthesis, thereby, decreasing TC and VLDL-C [100,101]. Consumption of soybean proteins also significantly reduced the severity of retinoic-acid induced hypertriglyceridemia in rats through the interaction with the retinoid receptors [102,217]. [PERSON] et al., (2008) found that soybean isolate consumption in rats elevated both hepatic c (RAR\(\beta\)) translation and/or through its post-translational modification(s), thus, suppressing its ability to bind to the DNA of its target genes to alleviate this retinoid-induced hypertriglyceridemia [103,104,218]. Soybean proteins also stimulated LDL receptor gene expression in cultured human hepatic cells [116,145,150] and in various animals such as rats [101,219], in moderate hypercholesterolemics [220], and in those with familial hypercholesterolemia and hypercholesterolic type 2 diabetic patients [221]. Aside from the reduced hepatic TAG levels, ingestion of soybean proteins also decreased epididymal adipose tissue weight and increased the expression of the skeletal muscle carnitine-palmitoyl transferase 1 (CPT1), a key enzyme involved in the transfer of fatty acids into the mitochondria to promote hepatic \(\beta\)-oxidation [222] and of the peroxisome proliferator-activated receptor-alpha (PPAR\(\alpha\)) in male Sprague Dawley rats [223]. It is the activation PPAR\(\alpha\) gene expression that leads to the activation of CPT1 in the rat liver [206]. CPT-1 is part of the mitochondrial fatty acid \(\beta\)-oxidation system that permits acyl-CoA to be transferred through the mitochondrial matrix and cross into the inner mitochondrial membrane to enter this fatty acid pathway [224]. In dogs, CPT-1 inhibition regulates this \(\beta\)-oxidation system and slows cardiac left ventricle remodeling and the deterioration of the function in pacing-induced heart failure [225]. The peroxisome proliferator-activated receptors (PPARs) including alpha (\(\alpha\)), beta (\(\beta\)), delta (\(\delta\)), and gamma (\(\gamma\)) are transcription activators that regulate glucose and lipid metabolism [226], including those for the 3-hydroxyl-CoA-dehydrogenase (HAD) and CPT-1 [226; 227; 228]. [PERSON] et al., (2009) found that PPAR\(\alpha\), and \(\beta/\delta\) inhibit the angiotensin-II mediated reduction of the fatty acid \(\beta\)-oxidation pathway by activating the TNF-\(\alpha\) in adult rat cardiac (ARC) myocytes [229]. PPAR\(\alpha\) regulates lipid metabolism in various tissues such as the heart, liver and skeletal muscle to decrease circulating lipid levels and improve hyperlipidemia. Stimulation of this transcription activator suppresses post-prandial lipidemia by enhancing fatty acid \(\beta\)-oxidation in enterocytes, thus, reducing circulating lipid levels [230]. Much like the other PPARs, PPAR\(\alpha\) promotes the expression of key enzymes involved in fatty acid oxidative metabolism [231; 232; 233]. In the nucleus of various cells including the myocardium, PPAR\(\alpha\) heterodimerizes with the retinoid X-receptors (RXR), a common nuclear receptor binding partner of the PPARs. The PPAR\(\alpha\)-RXR heterodimer binds to the DNA of their specific targets such as acyl-CoA [231; 234; 235; 236] and CPT-1 [231; 237] to activate the enzymes involved in lipid metabolism including that for free fatty acids. In healthy hearts, these free fatty acids serve as the primary energy source while a failing heart reverts back to a fetal metabolic pathway with reduced enzyme activity for free fatty acid oxidation [231; 238; 239].