The prevalence of ischemic heart disease (IHD) and diabetes mellitus type 2 (DM type 2) is permanently increasing both worldwide and in theRussian Federation. That is why studies of mechanisms of pathogenesis of both diseases is continuing for prevention of complications and mortality. DM type 2 contributes a lot to deterioration of IHD. One of pathogenetic features these two pathologies share is pronounced blood vessel wall fibrosis. In this review we present analysis of studies devoted to the determination of the role of metalloproteinase-9 and tissue inhibitor of metalloproteinases-1 indevelopment of vascular wall fibrosis.

Aim To determine levels of markers for endothelial dysfunction and inflammation, endothelin-1, E-selectin, and tumor necrosis factor α (TNF-α) in patients with ischemic heart disease (IHD) and non-obstructive and obstructive coronary artery (CA) disease.Material and methods This study included 32 patients with verified IHD and non-obstructive (main group, n=19) and obstructive (comparison group, n=13) CA disease. Endothelial dysfunction was diagnosed by photoplethysmography and videocapillaroscopy. Serum concentrations of endothelin-1, E-selectin, and TNF- α were measured in all patients.Results Patients with non-obstructive CA disease showed a tendency towards more pronounced endothelial dysfunction (alternative stiffness index, 7.8 m /s [6.35; 9.08]; reflection index, 36.95 % [23.4; 52.65]; capillary density following reactive hyperemia, 54.33 cap /mm2 [48.92; 75.83]; capillary density following venous occlusion, 74.33 cap /mm2 [67.83; 93.00]) compared to the comparison group (alternative stiffness index, 9.05 m/s [7.08; 10.58]; reflection index, 28.25 % [23.35; 53.75]; capillary density following reactive hyperemia, 66.83 cap /mm2 [50.83; 78.67]; capillary density following venous occlusion, 87.0 cap /mm2 [77.58; 78.67]), although statistically significant differences were not found. Concentration of endothelin-1 was significantly higher in the IHD group with non-obstructive CA disease (0.45 ng/ml [0.28;0.65]) compared to patients with CA atherosclerotic stenosis (0.35 ng/ml [0.25; 0.38], p=0.035). Concentrations of E-selectin did not significantly differ between the groups (main group, 21.1 ng/ml [18.45; 35.03]; comparison group, 28.55 ng/ml [19.08; 35.01], p=0.29). In both groups, concentrations of TNF-α did not exceed the lower threshold of sensitivity (<2.3 pg/ml).Conclusion Endothelial dysfunction and increased endothelin-1 in patients with non-obstructive CA disease along with inflammation may additionally contribute to the pathogenesis of IHD in the absence of hemodynamically significant CA stenoses. Too low level of TNFα in both groups prevented us from using it as a diagnostic marker. Further study is needed that would include a greater number of patients and a search for alternative markers.

Aim To determine concentration of the endothelial dysfunction (ED) marker, serum E-selectine, in patients with ischemic heart disease (IHD) in combination with type 2 diabetes mellitus (DM) and without DM.Material and methods The study included 60 IHD patients; 31 of them also had type 2 DM. E-selectin was measured in blood of all patients. In addition, a comprehensive evaluation of the morpho-functional condition of large blood vessels and microvasculature (MV) was performed by laser finger plethysmography (LFP) and nailfold computed videocapillaroscopy (CVC).Results Concentration of E-selectin was increased in IHD patients with type 2 DM (35.2 [29.0; 47.35] ng / ml vs. 31.7 [20.85; 36.68] ng / ml for IHD patients; p=0.028). A significant (p=0.018 and 0.016, respectively) decrease in the phase shift was observed in IHD patients with type 2 DM ( – 4.4 [ – 8.7; – 2.45] ms) compared to IHD patients ( – 1.9 [ – 3.95; – 0.38] ms). The capillary density evaluated in the venous occlusion test was reduced in IHD patients with type 2 DM (67.70 [57.83; 80.69]) compared to IHD patients (80.80 [69.05; 99.08]).Conclusion The signs of ED observed in patients of both groups were more pronounced in IHD patients with type 2 DM.

The prevalence of coronary heart disease (CHD) and type 2 diabetes mellitus (type 2 diabetes) in Russia and in the world continues to increase. Despite the prevention and optimization of therapy, CHD retains its leadership among all causes of death, and the mortality rate from type 2 diabetes and its complications gradually increases too. To improve the treatment of the above mentioned diseases, it is necessary to clarify the pathogenetic mechanisms of their development. The formation of endothelial dysfunction, characterized by an increase in the level of cell adhesion molecules and vasoconstriction, is a common link characteristic for the course and progression of CHD and type 2 diabetes. This article presents an analysis of preand clinical studies on the role of endothelial dysfunction markers: cell adhesion molecules (E-selectin), vasoconstriction (endothelin-1) and von Willebrand factor in patients with CHD, including those with type 2 diabetes mellitus.

Chronic heart failure (CHF) with preserved ejection fraction (CHFpEF) is an unsolved, socially relevant challenge since it is associated with a high level of morbidity and mortality. Early markers for this pathology are unavailable, and therapeutic approaches are undeveloped. This necessitates extensive studying the mechanisms of CHFpEF to identify therapeutic targets. According to current notions, systemic inflammation and endothelial dysfunction play an important role in the pathogenesis of CHFpEF. These processes induce the development of myocardial fibrosis and impairment of cardiomyocyte relaxation, thereby resulting in diastolic dysfunction and increased left ventricular (LV) filling pressure. Neuregulin-1 (NRG-1) is a paracrine growth factor and a natural agonist of ErbB receptor family synthesized in the endothelium of coronary microvessels. The NRG-1 / ErbB4 system of the heart is activated at early stages of CHFpEF to enhance the cardiomyocyte resistance to oxidative stress. Preclinical and clinical (phases II and III) studies have shown that the recombinant NRG-1 therapy results in improvement of myocardial contractility and in LV reverse remodeling. Results of recent studies suggest possible anti-inflammatory and antifibrotic effects of NRG-1, which warrants studying the activity of this system in patients with CHFpEF.