Diabetes mellitus comprises a group of carbohydrate metabolism disorders that share a common main feature of chronic hyperglycemia that results from defects of insulin secretion, insulin action, or both. Insulin is an important anabolic hormone, and its deficiency leads to various metabolic abnormalities in proteins, lipids, and carbohydrates. Atherosclerosis develops as a result of a multistep process ultimately leading to cardiovascular disease associated with high morbidity and mortality. Alteration of lipid metabolism is a risk factor and characteristic feature of atherosclerosis. Possible links between the two chronic disorders depending on altered metabolic pathways have been investigated in numerous studies. It was shown that both types of diabetes mellitus can actually induce atherosclerosis development or further accelerate its progression. Elevated glucose level, dyslipidemia, and other metabolic alterations that accompany the disease development are tightly involved in the pathogenesis of atherosclerosis at almost every step of the atherogenic process. Chronic inflammation is currently considered as one of the key factors in atherosclerosis development and is present starting from the earliest stages of the pathology initiation. It may also be regarded as one of the possible links between atherosclerosis and diabetes mellitus. However, the data available so far do not allow for developing effective anti-inflammatory therapeutic strategies that would stop atherosclerotic lesion progression or induce lesion reduction. In this review, we summarize the main aspects of diabetes mellitus that possibly affect the atherogenic process and its relationship with chronic inflammation. We also discuss the established pathophysiological features that link atherosclerosis and diabetes mellitus, such as oxidative stress, altered protein kinase signaling, and the role of certain miRNA and epigenetic modifications.

Cardiovascular pathologies maintain the leading position in mortality worldwide. Atherosclerosis is a chronic disease that can result in a variety of serious complications, such as myocardial infarction, stroke, and cardiovascular disease. Inflammation and lipid metabolism alterations play a crucial role in atherogenesis, but the details of relationships and causality of these fundamental processes remain not clear. The oxidation of LDL was considered the main atherogenic modification of LDL within the vascular wall for decades. However, recent investigations provided a growing body of evidence in support of the multiple LDL modification theory. It suggests that LDL particles undergo numerous modifications that change their size, density, and chemical properties within the blood flow and vascular wall. Oxidation is the last stage in this cascade resulting in the atherogenic properties. Moreover, recent investigations have discovered that oxLDL may have both anti-inflammatory and pro-inflammatory properties. Oxidized LDL can trigger inflammation through the activation of macrophages and other cells. After all, oxidized LDL is still a promising object for further investigations that have the potential to clarify the unknown parts of the atherogenic process. In this review, we discuss the role of oxLDL in atherosclerosis development on different levels.

Atherosclerosis is a predecessor of numerous cardiovascular diseases (CVD), which often lead to morbidity and mortality. Despite the knowledge of the pathogenesis of atherosclerosis, an essential gap in our understanding is the exact trigger mechanism. A wide range of risk factors have been discovered; however, a majority of them are too general to clarify the launching mechanism of atherogenesis. Some risk factors are permanent (age, gender, genetic heritage) and others can be modified [tobacco smoking, physical inactivity, poor nutrition, high blood pressure, type 2 diabetes (T2D), dyslipidemia, and obesity]. All of them have to be taken into account. In the scope of this review, our attention is focused on hypertension, which is considered the most widespread among all modifiable risk factors for atherosclerosis development. Moreover, high blood pressure is the most investigated risk factor. The purpose of this review is to summarize the data on hypertension as a risk factor for atherosclerosis development and the risk assessment.

People exposed to chronic stress age rapidly. The telomeres in their cells of all types shorten faster. Inflammation is another important feature of stress that, along with aging, accounts for the phenomenon of inflammaging. In addition to aging itself, inflammaging can contribute to the development of several pathologies, including atherosclerosis, diabetes, hypertension, and others. Oxidative stress is one of the main mechanisms related to stress. Oxidative stress is caused by the over-production of reactive oxygen species (ROS) that can damage various tissues. The main source of ROS is mitochondria. Being suppressed by mitochondrial mutations, mitophagy can aggravate the situation. In this case, the aging-specific pro-inflammatory changes are amplified. It happens because of the inability of cells to maintain the normal state of mitochondria. Macrophages are the crucial element of the innate immunity associated with the chronic inflammation and, subsequently, with the inflammaging. In this review, we focus on the therapy approaches potentially reducing the deleterious effects of oxidative stress. These include stimulation of mitophagy, activation of mitochondrial uncoupling, induction of the expression of the telomerase catalytic component gene, and use of antioxidants. Any method reducing oxidative stress should improve post-traumatic stress disorder.

Atherosclerosis can be regarded as chronic inflammatory disease affecting the arterial wall. Despite the recent progress in studying the pathogenesis of atherosclerosis, some of the pathogenic mechanisms remain to be fully understood. Among these mechanisms is oxidative stress, which is closely linked to foam cells formation and other key events in atherosclerosis development. Two groups of enzymes are involved in the emergence of oxidative stress: Pro-oxidant (including NADPH oxidases, xanthine oxidases, and endothelial nitric oxide synthase) and antioxidant (such as superoxide dismutase, catalases, and thioredoxins). Pro-oxidant enzymes in normal conditions produce moderate concentrations of reactive oxidant species that play an important role in cell functioning and can be fully utilized by antioxidant enzymes. Under pathological conditions, activities of both pro-oxidant and antioxidant enzymes can be modified by numerous factors that can be relevant for developing novel therapies. Recent studies have explored potential therapeutic properties of antioxidant molecules that are capable to eliminate oxidative damage. However, the results of these studies remain controversial. Other perspective approach is to inhibit the activity of pro-oxidant enzymes and thus to slow down the progression of atherosclerosis. In this review we summarized the current knowledge on oxidative stress in atherosclerosis and potential antioxidant approaches. We discuss several important antioxidant molecules of plant origin that appear to be promising for treatment of atherosclerosis.

Atherosclerosis has complex pathogenesis, which involves at least three serious aspects: inflammation, lipid metabolism alterations, and endothelial injury. There are no effective treatment options, as well as preventive measures for atherosclerosis. However, this disease has various severe complications, the most severe of which is cardiovascular disease (CVD). It is important to note, that CVD is among the leading causes of death worldwide. The renin–angiotensin–aldosterone system (RAAS) is an important part of inflammatory response regulation. This system contributes to the recruitment of inflammatory cells to the injured site and stimulates the production of various cytokines, such as IL-6, TNF-a, and COX-2. There is also an association between RAAS and oxidative stress, which is also an important player in atherogenesis. Angiotensin-II induces plaque formation at early stages, and this is one of the most crucial impacts on atherogenesis from the RAAS. Importantly, while stimulating the production of ROS, Angiotensin-II at the same time decreases the generation of NO. The endothelium is known as a major contributor to vascular function. Oxidative stress is the main trigger of endothelial dysfunction, and, once again, links RAAS to the pathogenesis of atherosclerosis. All these implications of RAAS in atherogenesis lead to an explicable conclusion that elements of RAAS can be promising targets for atherosclerosis treatment. In this review, we also summarize the data on treatment approaches involving cytokine targeting in CVD, which can contribute to a better understanding of atherogenesis and even its prevention.