**6. Oxidized low-density lipoproteins**

### **6.1. Pathogenesis of oxidized LDL**

In human organism, LDL particles undergo a series of oxidation processes, resulting in reactive oxygen species (ROS) and oxidized LDL (Ox-LDL) particles. These products create negative electric charges that will cause macrophagic stimulation and inflammation.

dysfunction by increasing endothelial adhesivity, by recruiting inflammatory cells into the

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Various studies have shown that Ox-LDL levels are associated with MetS. Holvoet et al. demonstrated that patients with MetS had higher Ox-LDL values. They also reported that hyperinsulinemia and impaired glycemic control were associated with increased Ox-LDL levels, independent from lipid levels. The same research found that elevated Ox-LDL levels could

Hurtado-Roca et al. in a study conducted on 3987 subjects demonstrated that Ox-LDL levels are positively correlated with MetS and its components even after adjustments for central obesity and insulin resistance. The strongest association was with triglyceride levels [27]. Another study conducted on overweighted/obese children showed that Ox-LDL positively correlated with BMI, percent body fat, waist circumference, percent trunk fat, abdominal visceral fat, abdominal subcutaneous fat (all p-values <0.0001), and with insulin resistance [28].

Pentraxins are a cluster of seric proteins with similar structures and calcium-dependent ligands that play important roles in body protection and in inflammatory mediation. The main mechanism is based on complement activation and interaction with Fc receptors [70].

PTX3 is being produced by immune cells as a response to bacterial substances, endotoxins, IL-1, and TNF-alpha. PTX3 is an acute phase protein with very low serum levels. PTX3 levels rise rapidly as a response to diverse inflammation stimuli. Therefore, PTX3 is considered to be

Recently, it has been shown that increased PTX3 levels are associated with MetS development and progression. In a study conducted on adolescent subjects with obesity, Kardas et al. have shown that subjects with obesity and MetS had higher values of PTX3 than the subjects without MetS. They also observed that low HDL cholesterol and high triglyceride levels were associated with increased PTX3 levels [29]. Also, Zanetti et al. demonstrated that PTX3 was higher in patients with MetS and subclinical atherosclerosis and that PTX3 was independently correlated with low HDL cholesterol levels [30]. Furthermore, a recent study found that PTX3 correlates with the severity of MetS, more precisely, after multivariate analysis PTX3 correlation persisted for glucose level (β = 0.23, p < 0.001), waist circumference (β = 0.37, p < 0.001), and HDL cholesterol (β = −0.31, p < 001) [31]. In conclusion, PTX3 could be a valu-

able biomarker in the prediction of MetS, but further studies should be conducted.

a marker of local and general inflammatory and immune response [71–73].

endothelial wall, and by reducing nitric oxide production **(Figure 6)** [68, 69].

**6.3. Oxidized LDL and metabolic syndrome**

predict the development of MetS in future [26].

**7.1. The role of pentraxins in human organism**

**7.2. Pentraxin-3 and metabolic syndrome**

**7. Pentraxin-3**

During LDL oxidation process, a series of products are generated: fatty acid oxidation products, lipid-derived products, protein oxidation products **(Figure 5)** [63].

Lara-Guzman et al. have shown that THP-1 human macrophage exposure to Ox-LDL caused a series of changes, such as an increased intake of Ox-LDL, overexpression of its receptors, and ROS production. Likewise, in the same study, it has been demonstrated that Ox-LDL determines the synthesis of isoprostanes as oxidation markers and of prostaglandines and prostaglandine metabolites as inflammation markers. Therefore, this study emphasizes that Ox-LDL links oxidative stress with inflammation via macrophages, resulting in systemic and local consequences [64]. Besides that, Schwarz et al. demonstrated that Ox-LDL increases Jun activation domain-binding protein-1 and stimulates inflammatory signaling in macrophages [65].

### **6.2. Oxidized LDL and endothelial dysfunction**

Atherosclerosis represents one of the main alterations caused by MetS, and endothelial dysfunction is the earliest event within it. As mentioned earlier, Ox-LDL triggers inflammation and oxidation process that determines macrophagic activation and ROS production with cytotoxic effect on vascular endothelium [66].

Ox-LDL interacts with lectin-type oxidized LDL receptor 1 (LOX-1) from the surface of endothelial cells and determines their activation [67]. Withal, Ox-LDL causes endothelial

**Figure 6.** LDL oxidation products.

dysfunction by increasing endothelial adhesivity, by recruiting inflammatory cells into the endothelial wall, and by reducing nitric oxide production **(Figure 6)** [68, 69].

## **6.3. Oxidized LDL and metabolic syndrome**

Various studies have shown that Ox-LDL levels are associated with MetS. Holvoet et al. demonstrated that patients with MetS had higher Ox-LDL values. They also reported that hyperinsulinemia and impaired glycemic control were associated with increased Ox-LDL levels, independent from lipid levels. The same research found that elevated Ox-LDL levels could predict the development of MetS in future [26].

Hurtado-Roca et al. in a study conducted on 3987 subjects demonstrated that Ox-LDL levels are positively correlated with MetS and its components even after adjustments for central obesity and insulin resistance. The strongest association was with triglyceride levels [27]. Another study conducted on overweighted/obese children showed that Ox-LDL positively correlated with BMI, percent body fat, waist circumference, percent trunk fat, abdominal visceral fat, abdominal subcutaneous fat (all p-values <0.0001), and with insulin resistance [28].
