**7. Pentraxin-3**

**Figure 6.** LDL oxidation products.

**6. Oxidized low-density lipoproteins**

**6.2. Oxidized LDL and endothelial dysfunction**

cytotoxic effect on vascular endothelium [66].

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 nega-

During LDL oxidation process, a series of products are generated: fatty acid oxidation prod-

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].

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

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

tive electric charges that will cause macrophagic stimulation and inflammation.

ucts, lipid-derived products, protein oxidation products **(Figure 5)** [63].

**6.1. Pathogenesis of oxidized LDL**

96 Ultimate Guide to Insulin

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

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

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

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