The influence of depression on risk development of acute cardiovascular diseases in the female population aged 25–64 in Russia

Background. Recent studies showed that depression was an independent predictor of mortality from cardio-vascular disease in healthy women. Objective. To explore the effect of depression (D) on relative risk (RR) of myocardial infarction (MI) and stroke for 16 years (1995–2010) in the female population aged 25–64 years from Novosibirsk, Russia. Materials and methods. Under the third screening of the WHO “MONICA-psychosocial” (MOPSY) programme, a cohort of women aged 25–64 years (N=560) was surveyed. Women were followed for 16 years for the incidence of MI and stroke (1995–2010). D was measured at the baseline examination by means of test “MOPSY”. Participants having stroke, MI, arterial hypertension, coronary artery diseases and diabetes in their medical history at the baseline were excluded from this analysis. Results. The prevalence of D in women aged 25–64 years was 55.2%. With the growth of D levels, positive self-rated health reduced and almost 100% of those women have complaints about their health, but considered the care of their health insufficient. Women with major D significantly extended negative behavioural habits: smoking and unsuccessful attempts to give up, low physical activity, and less likely to follow a diet (healthy food). Major D associated with high job strain and family stress. Relative risk (RR) of MI development in women with D during 16 years of study was higher in 2.53 cases (p<0.05) and risk of stroke was higher in 4.63 cases (p<0.05). Conclusions. The prevalence of D in women aged 25–64 years was >50%. Women with D had a 2.53-fold risk of MI and 4.63-fold risk of stroke during the 16 years of follow-up

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease