Metalloproteinase activity in heart is increased in mice treated with a low dose of corticosterone.

NAHUEL HERNAN FERNANDEZ MACHULSKY; VERONICA DANNUNZIO; TAMARA MAZO; RICARDO GELPI; LAURA SCHREIER; BIBIANA FABRE; GABRIELA BERG

CABA

Congreso; Joint meeting of bioscience societies. LXII Annual meeting of argentine society of clinical investigation (SAIC); 2017

Sociedad Argentina de Investigación Clínica

Continuous increase of glucocorticoids due to chronic activation ofthe pituitary axis is one of the consequences of chronic stress. Theknowledge of its effects on plaque vulnerability markers and cardiovasculardisease will help to elucidate different pathophysiologicalmechanisms. With this aim, we studied 15 C57BL/6j mice treated(TM) for 4 weeks with 35 μg/ml corticosterone and 15 control mice(CM). After euthanasia, heart, liver, adrenal glands, epididymal andintestinal adipose tissue (AT) were weighed. Serum lipid profile wasevaluated. We performed a zymography of homogenized cardiactissue and epididymal AT for measuring metalloprotease activity(MMPs). In isolated and isovolumetric hearts perfunded with Langendorfftechnique, we measured the left ventricle develop pressure(LVDP) and its response to ß adrenergic stimulus (Isoproterenol (iso)1 μM). Results: At the end of treatment, adrenal gland weight waslower in TM (0.002 (0.0002) vs 0.003 (0.0004) gr, p=0.03). Weightgain was observed in TM vs CM (5.0 (1.5-9.5) vs 3.3 (2.0-7.0) gr,p=0.007), at expense of epididymal AT (0.73 (0.06) vs. 0.33 (0.04) g,p <0.001), without differences in heart, liver or abdominal AT (p= ns).In TM, a higher concentration of triglycerides (98 (12) vs 63 (7) mg/dl, p=0.02) and total cholesterol (116 (11) vs 78 (4) mg/dl, p=0.002)was observed. In TM increased activity of MMP-9 (0.48 (0.42-0.49)vs 0.37 (0.34-0.40) relative units (RU), p = 0.01) in heart tissue andlower MMP-2 activity (1.03 (0.04) vs 1.26 (0.07) RU, p=0.01) in ATwas observed. Under baseline conditions, no differences in LVDPbetween TM and CT were observed. However, the response to Isowas lower in TM compared with CM (DLVDP: 14.9 vs 47.6 mmHg,p=0.02). Conclusions: After 4 weeks of treatment, we observed certaintypical metabolic consequences effects of glucocorticoids. Inaddition, the impact on heart evidenced through an increase in MMPactivity and a decrease in contractile reserve.