Role of thyroid hormones, TGF-β1 and ON in arterial hypertension generated by environmental toxins

DEZA Z; CASTILLA R; ROMERO CAIMI G; BONAZZOLA P; ALVAREZ L; GUTIERREZ C; CHIAPPINI F

Mar del Plata

Congreso; LXIV Reunión Anual de la Sociedad Argentina de Investigacion Clínica; 2019

Sociedad Argentina de Investigación Clínica, Sociedad Argentina de Inmunología, Sociedad Argentina de Farmacología Experimental, Sociedad Argentina de Biología

Hypertension is one of the main pathologies associated with environmental pollution. Among the environmental pollutants is hexachlorobenzene (HCB). We demonstrate that HCB increases blood pressure (BP) and alters morphology and vascular functionality (VF) in vivo. TGF-β1 and RE-α are involved in these effects. Since the effects on the VF were endothelium dependent, in this work we deepen the study of the mechanism of action of HCB on VF in the EA-hy926 endothelial line, grown in DMEM, 10% FBS, at 37 ° C treated with HCB (0.05, 0.05 and 5μM) at different times (18 and 24 hours). We analyze: a-Molecules involved in contractility and BP , TGF-β1 and RE-α [Western blot (W), RT-PCR]. b-Levels of eNOs and nitrites (W, Greiss). c-Role of TGF-β1 in the expression of RE-α (TGF-R RII inhibitor, SB431542). d-Rol of thyroid hormones (TH) in the expression of TGF-β1 and RE-α [serum depleted TH, exogenous T3 (10-7M)], since HCB is an endocrine disruptor and induces hypothyroxinemia, and that TH regulates the expression of these parameters.a-T TGF-β1 (protein) increased 24%, (p <0.05), HCB (0.05) and 38, 40% (p <0.01), HCB (0.05 and 5μM), its mRNA 28 and 36%, (p <0.01), HCB (0.05 and 5μM). RE-α decreased 28 and 36% (p <0.01), HCB (0.05 and 5 μM) (18, 24hs). b -eNOs decreased 25% (p <0.05), HCB (5μM), and nitrites 20% and 38% (p <0.05, p <0.01), HCB (0.05 and 5 μM) (24hs). Inhibition of RII TGF-β1 increased RE-α, HCB (5μM) (24hs).d-The TGF-β1 increase in TH depleted cells dose-dependent, contrary to RE-α. HCB and T3 administration normalized the effect of HCB on both parameters (24hs).HCB alters hormonal homeostasis, deregulates molecules involved in VF via TGF- and NO. TGF- and the decrease in NO decreased, in a paracrine manner, could be responsible for the effects observed in vivo in vascular muscle cells of animals treated with HCB, increasing BP.