Razina Nigmatullina

Disrupted Serotonergic and Sympathoadrenal Systems in Patients with Chronic Heart Failure May Serve as New Therapeutic Targets and Novel Biomarkers to Assess Severity, Progression and Response to Treatment

Background: It is well established that the serotonergic system (SS) plays important roles in the pathogenesis of cardiovascular diseases. However, the impact of serotonin and its inter-relation with the sympathoadrenal system (SAS) in chronic heart failure (CHF) is poorly understood. Methods: Utilizing high-performance liquid chromatography with electrochemical detection, we determined blood plasma levels of serotonin (5-hydroxy-triptamine, [5-HT]p), 5- hydroxy-indole-acetic acid ([5-HIAA]p), epinephrine ([E]p), norepinephrine ([NE]p), 3,4-dihydroxy-L-phenyl-alanine ([DOPA]p), dopamine ([DA]p) and the platelet concentration of serotonin ([5-HT]pt) in CHF patients with different morphofunctional alterations of myocardium. The morphofunctional alterations included diastolic dysfunction (DD), diastolic dysfunction with left ventricular hypertrophy (DD&LVH), and diastolic and systolic dysfunction (D&SD). Results: All CHF groups showed significant rises of [5-HT]p and [5-HT]pt. DD&LVH and D&SD individuals also had increased [5-HIAA]p. Levels of SAS blood biomarkers were also significantly changed. The correlation between SS and SAS was increased in CHF and corresponded with disease severity. Conclusions: These results clearly demonstrate that in CHF patients significant changes in SS and SAS occur, which are thought to relate to the morphofunctional alterations of myocardium. The observed changes in the levels of these biomarkers may serve as potential surrogates to monitor severity of disease, to evaluate response to drug treatment, and as a rational basis for new therapeutic approaches.

Increased concentrations of serotonin and 5-hydroxyindoleacetic acid in blood plasma from patients with pulmonary hypertension due to mitral valve disease.

Serotonin content in the plasma and platelets and 5-hydroxyindoleacetic acid concentration in the plasma were shown to increase in patients with pulmonary arterial hypertension due to mitral valve disease. A positive correlation was found between the severity of pulmonary arterial hypertension and concentrations of serotonin (r=0.48) and 5- hydroxyindoleacetic acid in the plasma (r=0.9).

Upgraded Methodology for the Development of Early Diagnosis of Parkinson’s Disease Based on Searching Blood Markers in Patients and Experimental Models

Numerous attempts to develop an early diagnosis of Parkinson’s disease (PD) by searching biomarkers in biological fluids were unsuccessful. The drawback of this methodology is searching markers in patients at the clinical stage without guarantee that they are also characteristic of either preclinical stage or prodromal stage (preclinical–prodromal stage). We attempted to upgrade this methodology by selecting only markers that are found both in patients and in PD animal models. HPLC and RT-PCR were used to estimate the concentration of amino acids, catecholamines/metabolites in plasma and gene expression in lymphocytes in 36 untreated early-stage PD patients and 52 controls, and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice at modeling the clinical (“symptomatic”) stage and preclinical–prodromal (“presymptomatic”) stage of PD. It was shown that among 13 blood markers found in patients, 7 markers are characteristic of parkinsonian symptomatic mice and 3 markers of both symptomatic and presymptomatic mice. According to our suggestion, the detection of the same marker in patients and symptomatic animals indicates adequate reproduction of pathogenesis along the corresponding metabolic pathway, whereas the detection of the same marker in presymptomatic animals indicates its specificity for preclinical–prodromal stage. This means that the minority of markers found in patients—decreased concentration of l-3,4-dihydroxyphenylalanine (l-DOPA) and dihydroxyphenylacetic acid (DOPAC) and increased dopamine D3 receptor gene expression—are specific for preclinical–prodromal stage and are suitable for early diagnosis of PD. Thus, we upgraded a current methodology for development of early diagnosis of PD by searching blood markers not only in patients but also in parkinsonian animals.

Nitrogen Oxide, Endothelin-1, and Serotonin in the Blood of Immature Spontaneously Hypertensive Rats

Endothelial function is an early and sensitive marker of subclinical increase of BP in children and adolescents. It is associated with an imbalance of the key vasoactive factors (NO, endothelin-1, and serotonin). Immature spontaneously hypertensive rats (SHR line) are characterized by increased plasma concentrations of NO and endothelin-1 (by 14.7% and 2.9 times, respectively) and increased serotonin content in the plasma and platelets (by 2.7 and 2.3 times, respectively) in comparison with Wistar-Kyoto rats. Platelet count in the blood of SHR rats is by 50% higher than in Wistar-Kyoto rats.