Expansive Vascular Remodeling and Increased Vascular Calcification Response to Cholecalciferol in a Murine Model of Obesity and Insulin Resistance.

Autor: Carmo LS; From the Department of IIEP-Research and Teaching Institute (L.S.C., M.R.F., Y.E.A., L.A.P., E.F.-S., L.F.G., G.H.L., T.P.A.A., M.L.), Hospital Israelita Albert Einstein, São Paulo, Brazil.; the Division of Nephrology, LIM 12, University of São Paulo Medical School, Brazil (L.S.C., E.A.B.)., Burdmann EA; the Division of Nephrology, LIM 12, University of São Paulo Medical School, Brazil (L.S.C., E.A.B.)., Fessel MR; From the Department of IIEP-Research and Teaching Institute (L.S.C., M.R.F., Y.E.A., L.A.P., E.F.-S., L.F.G., G.H.L., T.P.A.A., M.L.), Hospital Israelita Albert Einstein, São Paulo, Brazil., Almeida YE; From the Department of IIEP-Research and Teaching Institute (L.S.C., M.R.F., Y.E.A., L.A.P., E.F.-S., L.F.G., G.H.L., T.P.A.A., M.L.), Hospital Israelita Albert Einstein, São Paulo, Brazil., Pescatore LA; From the Department of IIEP-Research and Teaching Institute (L.S.C., M.R.F., Y.E.A., L.A.P., E.F.-S., L.F.G., G.H.L., T.P.A.A., M.L.), Hospital Israelita Albert Einstein, São Paulo, Brazil., Farias-Silva E; From the Department of IIEP-Research and Teaching Institute (L.S.C., M.R.F., Y.E.A., L.A.P., E.F.-S., L.F.G., G.H.L., T.P.A.A., M.L.), Hospital Israelita Albert Einstein, São Paulo, Brazil., Gamarra LF; From the Department of IIEP-Research and Teaching Institute (L.S.C., M.R.F., Y.E.A., L.A.P., E.F.-S., L.F.G., G.H.L., T.P.A.A., M.L.), Hospital Israelita Albert Einstein, São Paulo, Brazil., Lopes GH; From the Department of IIEP-Research and Teaching Institute (L.S.C., M.R.F., Y.E.A., L.A.P., E.F.-S., L.F.G., G.H.L., T.P.A.A., M.L.), Hospital Israelita Albert Einstein, São Paulo, Brazil., Aloia TPA; From the Department of IIEP-Research and Teaching Institute (L.S.C., M.R.F., Y.E.A., L.A.P., E.F.-S., L.F.G., G.H.L., T.P.A.A., M.L.), Hospital Israelita Albert Einstein, São Paulo, Brazil., Liberman M; From the Department of IIEP-Research and Teaching Institute (L.S.C., M.R.F., Y.E.A., L.A.P., E.F.-S., L.F.G., G.H.L., T.P.A.A., M.L.), Hospital Israelita Albert Einstein, São Paulo, Brazil.; Department of Critical Care Medicine and Cardiology (M.L.), Hospital Israelita Albert Einstein, São Paulo, Brazil.
Jazyk: angličtina
Zdroj: Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2019 Feb; Vol. 39 (2), pp. 200-211.
DOI: 10.1161/ATVBAHA.118.311880
Abstrakt: Objective- We hypothesized that ob/ob mice develop expansive vascular remodeling associated with calcification. Approach and Results- We quantified and investigated mechanisms of vascular remodeling and vascular calcification in ob/ob mice after vitamin D 3 (VD) stimulation or PBS (control), compared with C57BL/6 mice. Both ob/ob (OBVD [VD-treated ob/ob mice]) and C57BL/6 (C57VD [VD-treated C57BL/6 mice]) received 8×10 3 IU/day of intraperitoneal VD for 14 days. Control ob/ob (OBCT [PBS-treated ob/ob mice]) and C57BL/6 (C57CT [PBS-treated C57BL/6 mice]) received intraperitoneal PBS for 14 days. Hypervitaminosis D increased the external and internal elastic length in aortae from OBVD, resulting in increased total vascular area and lumen vascular area, respectively, which characterizes expansive vascular remodeling. OBVD decreased the aortic wall thickness, resulting in hypotrophic vascular remodeling. We demonstrated increased collagen deposition, elastolysis, and calcification in aortae from OBVD. Our results showed a positive correlation between expansive vascular remodeling and vascular calcification in OBVD. We demonstrated increased serum calcium levels, augmented Bmp (bone morphogenetic protein)-2 and osteochondrogenic proteins expression in OBVD aortae. Furthermore, aortae from OBVD increased oxidative stress, coincidently with augmented in situ MMP (matrix metalloproteinase) activity and exhibited no VDR (VD receptor) inhibition after VD. Conclusions- Our data provide evidence that obese and insulin-resistant mice (ob/ob) developed expansive hypotrophic vascular remodeling correlated directly with increased vascular calcification after chronic VD stimulation. Positive hypotrophic vascular remodeling and vascular calcification in this mouse model is possibly mediated by the convergence of absence VDR downregulation after VD stimulation, increased reactive oxygen species generation, and MMP activation.
Databáze: MEDLINE
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