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Several epidemiological studies have clearly shown the high co-morbidity between depression and Cardiovascular Diseases (CVD). Different studies have been conducted to identify the common pathophysiological events of these diseases such as the overactivation of the hypothalamic- pituitary-adrenal axis and, most importantly, the dysregulation of immune system which causes a chronic pro-inflammatory status. The biological link between depression, inflammation, and CVD can be related to high levels of pro-inflammatory cytokines, such as IL-1β, TNF-α, and IL-6, released by macrophages which play a central role in the pathophysiology of both depression and CVD. Pro-inflammatory cytokines interfere with many of the pathophysiological mechanisms relevant to depression by upregulating the rate-limiting enzymes in the metabolic pathway of tryptophan and altering serotonin metabolism. These cytokines also increase the risk to develop CVD, because activation of macrophages under this pro-inflammatory status is closely associated with endothelial dysfunction and oxidative stress, a preamble to atherosclerosis and atherothrombosis. Carnosine (β-alanyl-L-histidine) is an endogenous dipeptide which exerts a strong antiinflammatory activity on macrophages by suppressing reactive species and pro-inflammatory cytokines production and altering pro-inflammatory/anti-inflammatory macrophage polarization. This dipeptide exhibits antioxidant properties scavenging reactive species and preventing oxidative stress-induced pathologies such as CVD. In the present review we will discuss the role of oxidative stress and chronic inflammation as common pathophysiological events both in depression and CVD and the preclinical and clinical evidence on the protective effect of carnosine in both diseases as well as the therapeutic potential of this dipeptide in depressed patients with a high co-morbidity of cardiovascular diseases.

Nitric oxide (NO) is involved in many biological functions, including blood pressure regulation, the immune response, and neurotransmission. However, excess production of NO can lead to the generation of reactive nitrogen species and nitrosative stress and has been linked to several neurodegenerative diseases and cardiovascular disorders. Because NO is short-lived and generally difficult to detect, its primary stable degradation product, nitrite, is frequently monitored in its place. In this paper, an improved method using microchip electrophoresis with electrochemical detection (ME-EC) was developed for the separation and detection of nitrite in cell lysates. A separation of nitrite from several electroactive cell constituents and interferences was optimized, and the effect of sample and buffer conductivity on peak efficiency was explored. It was found that the addition of 10 mM NaCl to the run buffer caused stacking of the nitrite peak and improved limits of detection. A platinum black working electrode was also evaluated for the detection of nitrite and other electroactive cellular species after electrophoretic separation. The use of a modified platinum working electrode resulted in 2.5-, 1.7-, and 7.2-fold signal enhancement for nitrite, ascorbic acid, and hydrogen peroxide, respectively, and increased the sensitivity of the method for nitrite 2-fold. The optimized ME-EC method was used to compare nitrite production by native and lipopolysaccharide-stimulated RAW 264.7 macrophage cells.

Carnosine, a dipeptide found in a variety of tissues, is believed to possess antioxidant properties. It serves as a scavenger of reactive nitrogen and oxygen species (RNOS), which are important stress mediators of pro-inflammatory conditions and can lead to macrophage activation. In this study, intracellular concentrations of carnosine in murine RAW 264.7 macrophage cells were determined using microchip electrophoresis with laser-induced fluorescence detection following derivatization with naphthalene-2,3-dicarboxaldehyde and cyanide. The method was linear from 25 nM to 5 μM with a limit of detection in cell lysate samples of 65 nM. Using the method of standard additions, the basal intracellular content of carnosine in macrophage cells was determined to be 0.079 ± 0.02 nmol per 106cells. The uptake of carnosine by these cells was then investigated under both physiological and pro-inflammatory conditions. There was a 2.8-fold increase in carnosine uptake for macrophages exposed to lipopolysaccharides and interferon-γ prior to incubation, compared to the controls. This suggests that macrophages may use carnosine uptake as a defense mechanism under pro-inflammatory conditions. Future studies will investigate the role of the carnosine transporter in carnosine uptake and its possible correlation with cell morphological changes observed after stimulation.