**3. Conclusions**

character of the mutual effects between the activity of the inflammatory processes

Despite this, many hypotheses have been proposed regarding the association of elevated CRP values with depression using various covariates that can affect these relationships: from BMI and general physical health to the type of depression, which makes it likely that there is a multifactorial and bi-directional relationship between

Frasure-Smith et al. demonstrated that the association between CRP level and depression is important for predicting future adverse cardiovascular events [65]. There is a lot of evidence in the scientific literature about significant and sustained elevations of CRP level in depressed patients, which may or may not normalize after remission of depression symptoms, indicating a continued possibility of adverse

In 2015, the results of Setiawan E. et al. were published, where authors concluded that depression causes inflammation. The researchers obtained the first nonexperimental evidence that besides neurons, glial cells, namely, microglia, play an important role in depressive disorders [67]. However, despite these findings, it is difficult to conclude that depressive disorders are a trigger of inflammation. It is possible that stress and other risk factors lead to depressive disorders that affect the activation of microglia and a change in its structure, in turn, increasing the level of depression, i.e., it may be a continuum. The data obtained in the present study on the reduction of the level of depression (p < 0.05) accompanied by a decrease in the inflammatory activity of the endothelium with the help of a therapy that does not have an antidepressant effect also suggest the two-sided associations between

ED is a vascular phenotype that predisposes to atheromatosis and atherosclerosis

Endothelial dysfunction can lead to immunological changes, activation, adhesion of white blood cells, and aggregation of platelets in the vascular damage area. The attachment of monocytes and lymphocytes to endothelial cells is associated with the activation of cell adhesion molecules [69]. Chronic mild inflammation is known as a predictor of myocardial infarction and ischemic stroke. ED is a "critical intermediate phenotype" in the association between mild inflammation and CVD. ED can be considered as an "intermediate phenotype" in depression based on the presence of mild chronic inflammation in many patients with depressive symptoms [70]. Depression can be regarded as a chronic stressor that contributes to the development of ED due to the disruption of cell adhesion, platelet hypercoagulation. Depression is associated with higher levels of MCP-1, p-selectin, and others. Some researchers consider ED as a biomarker of arterial atheromatosis, which can be a sign of depression [71]. The present study has shown that there are strong associations between inflammatory markers and markers of proatherogenic activity (endothelin-1, CECs, and fibrinogen). Based on the values of CRP, MCP-1, endothelin-1, CECs, and fibrinogen, an integrative indicator of endothelial dysfunction had higher values in patients with clinically significant depression, compared with patients with subclinical depression (p < 0.01). An inverse statistically significant correlation was found between the integrative endothelial dysfunction index and severity of depression (r = 0.83; p < 0.05). Moreover, this association between the integrative endothelial dysfunction index and depression did not depend on age, type 2 diabetes mellitus, and obesity (p < 0.001)—the risk factors

Do et al. focused on the association of individual symptoms of depression (a symptom of hopelessness that can turn into suicidality) with markers of ED.

cardiovascular events even after recovery from depression [66].

and, therefore, may be a predictor of cardiovascular events [68].

and the level of depression.

depression and inflammation [64].

*Basic and Clinical Understanding of Microcirculation*

inflammation and depression.

known to raise the incidence of CVD.

**112**

Despite growing evidence that underlines the bilateral relationship between depression and CVD and the fact that the mechanisms of their connection were partially identified (e.g., inflammation, ED), further research with a large sample size is required.

Novel pharmacological approaches based on discoveries related to the immune and neurotransmitter systems are in high demand.

The development and implementation of preventive measures and lifestyle correction, which can reduce the burden of cerebrovascular diseases and depression, are required as well.
