EFFECT OF OBESITY PRESENCE ON INSULIN-LIKE GROWTH FACTOR-1 AND ENDOSTATIN IN PATIENTS WITH MYOCARDIAL INFARCTION.

Aim of the study - to study the markers of angiogenesis‒IGF-1 and endostatin ‒ in patients with acute myocardial infarction according to the presence or absence of obesity. The study involved 105 patients with acute myocardial infarction (MI) with concomitant obesity who were treated in the infarctional department (mean age 64.6±7.4 years), 55 of them ‒ with acute MI with comorbidant obesity and 60 patients ‒ with acute MI without obesity. The groups were comparable by sex and age. The control group consisted of 20 healthy persons of corresponding age and sex. In obese and non-obese patients with MI the levels of IGF-1 were statistically significantly higher than those of persons in the control group (p<0.05). The levels of IGF-1 in acute MI with obesity were statistically significantly higher than in the serum of patients with MI without obesity (180.64±12.2 ng/ml and 128.76±8.1 ng/ml, accordingly, p<0.05). Patients with acute MI showed increased IGF-1 and endostatin in comparison with the controls. The presence of obesity in MI was accompanied by an increased IGF-1 and decreased endostatin as compared to patients with MI. In patients with MI and obesity, high activity of IGF-1 was accompanied by high levels of proaterogenic lipids with reduced volumes and thickening of the interventricular wall of the left ventricle. Unlike IGF-1 hyperendostatinemia was associated with left ventricle dilation.

Systemic injection of AAV9-GDNF provides modest functional improvements in the SOD1G93A ALS rat but has adverse side effects.

Injecting proteins into the central nervous system that stimulate neuronal growth can lead to beneficial effects in animal models of disease. In particular, glial cell line-derived neurotrophic factor (GDNF) has shown promise in animal and cell models of Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis (ALS). Here, systemic AAV9-GDNF was delivered via tail vein injections to young rats to determine whether this could be a safe and functional strategy to treat the SOD1G93A rat model of ALS and, therefore, translated to a therapy for ALS patients. We found that GDNF administration in this manner resulted in modest functional improvement, whereby grip strength was maintained for longer and the onset of forelimb paralysis was delayed compared to non-treated rats. This did not, however, translate into an extension in survival. In addition, ALS rats receiving GDNF exhibited slower weight gain, reduced activity levels and decreased working memory. Collectively, these results confirm that caution should be applied when applying growth factors such as GDNF systemically to multiple tissues.