Changes Of Extracellular Matrix Metalloproteinase-2 Of Isoproterenol Injured Normotensive And Hypertensive Rats Are Hampered By Treatment With Omega-3 Fatty Acids And Melatonin
JOURNAL OF HYPERTENSION(2018)
Abstract
Objectives: Experimental and clinical studies suggest that melatonin and omega-3 fatty acids (PUFA) are cardioprotective, but underlying molecular mechanisms are still not fully explored. We hypothesize that both compounds may affect extracellular matrix remodeling by modulation of extracellular matrix metalloproteinases (MMP) activity. We aimed to explore MMP-2 activity in plasma, aorta and heart in normotensive and hypertensive rats after infarct-like cardiac injury induced by high dose of isoproterenol (ISO) as well as the effects of treatments with PUFA and melatonin. Methods: We used in our experiment Wistar (W) and spontaneously hypertensive rats (SHR) which were divided into four groups. 1)Controls without treatment; 2)Iso-injured rats (118 mg/kg totally, s.c./7days); 3)Iso-injured rats treated with melatonin (10 mg/kg, p.o., 2-mo); 4)Iso-injured rats treated with PUFA (Omacor, 1.68 g/kg, p.o.,2-mo). Samples from plasma, left and right ventricles and aorta were used to determine activity of MMP-2 by using gelatin zymography. Results: There was higher plasma but lower heart tissue-related MMP-2 activity in non-treated SHR vs W rats and no difference in aorta. ISO caused an increase of MMP-2 activity in plasma as well as in atria and decrease in left and right ventricles of W rats. In contrast, ISO decreased MMP-2 activity in plasma, aorta and increased in left and right ventricles of SHR. Melatonin and Omacor suppressed plasma MMP-2 activity in Iso-treated W but not in Iso-SHR. Both compounds lowered MMP-2 activity in atria of Iso-W rats but elevated in iso-SHR as well as decreased MMP-2 activity in ventricles of Iso-treated SHR only. Conclusion: Data indicates that both melatonin and Omacor modulate circulating and cardiovascular tissue-related MMP-2 activity. Supported:VEGA 2/0167/15, 2/0076/12; APVV-15-0119
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Key words
omega-3 fatty acids, melatoninm, matrix metalloproteinase-2
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