**4.4 How the gut microbiota affects on vascular endothelium**

Gut microbiota is the collection of bacteria that inhabitat gastrointestinal tract and have many repercussions in health. Several studies have indicated that gut microbiota plays a contributing role in atherosclerosis through modulating inflammation and the

secretion of microbial metabolites. Recent studies have shown the influence of gut disbiosis and progression of atherosclerosis and cardiovascular disease. Bacteria such as *Akkermansia muciniphila* promote barrier function and have attenuating effect against atherosclerosis [27].

Scientists have found that the relative abundance of Roseburia and Eubacterium was lower, while Collinsella was higher in atherosclerosis patients compared with healthy controls [28].

Variety of metabolites are derived from the gut microbiota, as well as co-metabolism of gut microbiota such as amines methylamines, polyamines, short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), and secondary bile acids (BAs). SCFAs are a group of well-established gut microbial metabolites that are critically involved in metabolic diseases [27].

Diet has an important role in biodiversity of microbiome and hemostasis for maintaining human health. Disbiosis has been associated with progression of various diseases including CVD, obesity, diabetes, nonalcoholic fatty liver disease, and some types of cancer.

#### **4.5 Molecular endothelial dysfunction in obesity**

There are many bioquimical makers of endothelial dysfunction: first MCP1 (monocyte chemotactic and activating factor). This protein is synthesized by several types of cells, including inflammatory and inflammation-mediated cells, monocytic cells, human tubular epithelial cells (TECs), and renal-mediated cells in response to various stimuli and when joint to chemokine receptor 2 (CCR2) initiates various monocyte-mediated proinflammatory signals and monocyte chemoattractant activities, facilitating monocytes migration to the subendothelium and combines with ox-LDL to form foam cells, forming a fatty streak and eventual atherosclerotic plaque (**Figure 4**) [29].

## **5. Obesity and atherosclerosis**

Obesity increases morbidity and mortality especially when associated to hypertension and CAD [30].

Obesity is associated with overt atherosclerotic lesions even after accounting for the impact of these metabolic cardiovascular risk factors. The association of obesity with raised atherosclerotic lesions among men in the Pathobiological Determinants of Atherosclerosis in Youth study was present only for those with a thick abdominal panniculus, indicating the fundamental role of central adiposity in the development of atherosclerotic disease [31]. Chronic inflammation induced by obesity increases the likelihood of low-density lipoprotein oxidation, which promotes atherogenesis [32]. Other factors together increase atherosclerosis are insulin resistance and metabolic syndrome.

Endothelial dysfunction in obesity is principally caused by diminished bioavailability of nitric oxide in the setting of inflammation and oxidative stress [33].

A prospective study published by Whintlock et al. describes an increase of probability of mortality stroke in a range of 25–50 kg/m2, each 5 kg/m2 is associated with 40% higher stroke mortality. A prospective cohort study with 3.2 million person-year by follow-up from 1964 to 2015 concluded that overweight and obesity shortened longevity and increased lifetime risk [34].

*Obesity and Cardiovascular Risk DOI: http://dx.doi.org/10.5772/intechopen.106877*

#### **Figure 4.** *Bioquimical markers of endothelial dysfunction.*

There are important differences in obesity according to gender that must be taken into account, such as the impact of hormones in women against the development of atherosclerosis.

Before menopause, women generally have greater vagal than sympathetic tone, and lower levels of total cholesterol and LDL-C than men. Additionally, differences in glucose and lipid metabolism, sex hormones, and cytokine production are thought to explain why men are at an increased risk of CVD [35, 36]. This recalls the protective effect of estrogens in maintaining health and distribution of body fat. This is likely explained by the aforementioned differences in hormone-driven patterns of fat distribution, with men more likely to deposit visceral fat, compared with subcutaneous fat in women, considering that visceral fat has been associated with greater cardiometabolic risk [37, 38].

Obesity is characterized by an increased risk of diabetes, hypertension, and dyslipidemia, and independently associated with CVD. Several prospective epidemiological studies demonstrate that obesity is associated with higher risk of incident coronary artery disease [39]. There are controversies if obesity causes high risk of CVD or the complications of obesity are the cause of them. Some large prospective analyses have indicated that the link between obesity and CAD is mediated largely by hypertension, dyslipidemia, diabetes, and other comorbidities, whereas other prospective studies suggest a significant residual CAD risk in obesity even after accounting for these risk factors [40].

A meta-analysis of 21 studies including 1.8 million individuals suggested that approximately half of the associations of overweight and obesity with CAD are explained by levels of blood pressure, cholesterol, and glucose [41]. There are three mechanisms linked to metabolic syndrome, that is, production of adipocytokines, oxidative stress, and a prothrombotic state [42].

Other important causative factor is the ectopic fat deposition, especially pericardial and epicardial spaces, which may further contribute to the burden of coronary atherosclerosis [43].

Some studies of pathobiology have shown that arteries with intramyocardial course in perfect condition could have atherosclerosis in epicardial segment of the same artery. Thus, local production of adipocytokines by epicardial fat may modulates blood vessel biology through paracrine signaling or through vasa vasorum [44].
