# Lycopene: A Natural Arsenal in the War against Oxidative Stress and Cardiovascular Diseases
## 5 Lycopene in Cardiovascular Diseases (CVDs)
### Coronary Artery Disease (CAD) and Lycopene  
Cardiovascular diseases with more that 17 million deaths every year include one of the major causes of death worldwide. CAD, which has become almost epidemic in many societies, is the most prominent CVD [183]. It is a chronic inflammatory disease caused by the remodeling of coronary arteries due to the narrowing of internal passage and hardening of vessels by plaque formation [184; 185]. In addition to the above, the activation of platelets and inflammatory factors also contribute to reduce the blood flow to the heart muscles, reducing the supply of oxygen and nutrients [186], especially during vigorous exertion. Atherosclerosis is a silent and gradual process demonstrated by the accumulation of low-density lipids and inflammatory factors in the arteries [187; 188; 189]. Oxidized low-density lipoprotein cholesterol LDL-C is the main contributor to the development of atherosclerosis and subsequent CAD via the activation and differentiation of monocytes to macrophages [191]. Macrophages interact with LDL-C, and the production of interleukins, cytokines, and tumor necrosis factors is induced. All these molecules contribute to the formation of first lesion of atherosclerosis [192; 193]. The smooth muscle cells are migrated to the intima from the medial layer of the artery, leading to the formation of a fibrous cap over the streak of lipid materials and subsequent formation of second lesion of atherosclerosis (plaque) [194]. The nature of the fibrous cap determines the properties of the plaque. Stable plaque is composed of an intact cap of smooth muscle cells in combination with collagen type I and III. Such a type of plaque results in stenosis, reduces the blood flow, and results in ischemia [195]. The second type of plaque, thin vulnerable plaques, is made up of type I collagen in combination with only a few smooth muscle cells. However, it contains a major proportion of proinflammatory molecules, macrophages, andthrombotic molecules [196; 197]. These plaques can erode or rapture, while the coagulatory proteins circulating in the blood can interact with them, resulting in thrombosis and acute coronary syndrome [198; 199]. Chronic CAD can cause heart failure [200], altered heart rate [201], myocardial ischemia, and left ventricular dysfunction [202]. In epidemiological research, the risk pattern for coronary artery disease has been thoroughly investigated. Age, male sex, raised LDL-C levels, low HDL-C levels, diabetes mellitus, food, genetics, and cigarette smoking are prominent risk factors for coronary heart disease [203; 204; 205; 206]. Obesity and metabolic disorders are also considered as the risk factors for CAD [36; 207]. Lycopene suppresses the formation of vascular smooth muscle cells (VSMCs) and foam cells, both of which have anti-atherosclerotic characteristics [208; 209; 210]. Contractile VSMCchange into proliferative and migratory cells during the atherosclerotic process, allowing them to move into the intima and build the plaque's extracellular matrix [211]. Phenotypic modulation refers to phenotypic alterations that are important in vascular remodeling, which might result in atherosclerosis, hypertension, or diabetic macroangiopathy [212]. Lycopene prevents G1 phase cells from entering the S phase of the cell cycle [213], not by inhibiting matrix metalloproteinase [214]. It was also found that minimally oxidized LDL-C can cause VSMC phenotypic modification; to suppress this process, lycopene may inhibit oxidized LDL formation [215; 216]. Direct binding to platelet-derived growth factor (PDGF) and reducing PDGF signaling [217] or acting as an antioxidant, since reactive oxygen species speed up the switch from contractile to synthetic phenotype [218], were observed to limit VSMC proliferation and migration. Lycopene also suppresses apoptosis in endothelial cells in vitro by interrupting the upregulation of p53 and caspase 3 mRNA, and prevents cluster of differentiation 14 (CD14) and toll-like receptor-4 expression in the endothelium membrane [219; 220].