1. Hyperdynamic circulatory syndrome in a mouse model transgenic for SerpinB3.
- Author
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Villano G, Verardo A, Martini A, Brocco S, Pesce P, Novo E, Parola M, Sacerdoti D, Di Pascoli M, Fedrigo M, Castellani C, Angelini A, Pontisso P, and Bolognesi M
- Subjects
- Angiotensin II Type 1 Receptor Blockers pharmacology, Animals, Antigens, Neoplasm pharmacology, Cardiac Output, Hemodynamics drug effects, Hepatic Artery diagnostic imaging, Hepatic Artery physiopathology, Humans, Irbesartan pharmacology, Mesenteric Arteries drug effects, Mice, Mice, Inbred C57BL, Mice, Transgenic, Microvessels drug effects, Phenylephrine pharmacology, Pulsatile Flow drug effects, Pulsatile Flow genetics, Rats, Rats, Inbred WKY, Serpins pharmacology, Splanchnic Circulation drug effects, Syndrome, Ultrasonography, Vasoconstriction drug effects, Vasoconstriction genetics, Vasodilation drug effects, Vasodilation genetics, Antigens, Neoplasm genetics, Hemodynamics genetics, Serpins genetics, Splanchnic Circulation genetics
- Abstract
Introduction and Objectives: SerpinB3 is a cysteine protease inhibitor involved in several biological activities. It is progressively expressed in chronic liver disease, but not in normal liver. The role in vascular reactivity of this serpin, belonging to the same family of Angiotensin II, is still unknown. Our aim was to evaluate the in vivo and in vitro effects of SerpinB3 on systemic and splanchnic hemodynamics., Material and Methods: Different hemodynamic parameters were evaluated by ultrasonography in two colonies of mice (transgenic for human SerpinB3 and C57BL/6J controls) at baseline and after chronic carbon tetrachloride (CCl
4 ) treatment. In vitro SerpinB3 effect on mesenteric microvessels of 5 Wistar-Kyoto rats was analyzed measuring its direct action on: (a) preconstricted arteries, (b) dose-response curves to phenylephrine, before and after inhibition of angiotensin II type 1 receptors with irbesartan. Hearts of SerpinB3 transgenic mice and of the corresponding controls were also analyzed by morphometric assessment., Results: In SerpinB3 transgenic mice, cardiac output (51.6±21.5 vs 30.1±10.8ml/min, p=0.003), hepatic artery pulsatility index (0.85±0.13 vs 0.65±0.11, p<0.001) and portal vein blood flow (5.3±3.2 vs 3.1±1.8ml/min, p=0.03) were significantly increased, compared to controls. In vitro, recombinant SerpinB3 had no direct hemodynamic effect on mesenteric arteries, but it increased their sensitivity to phenylephrine-mediated vasoconstriction (p<0.01). This effect was suppressed by inhibiting angiotensin II type-1 receptors., Conclusions: In transgenic mice, SerpinB3 is associated with a hyperdynamic circulatory syndrome-like pattern, possibly mediated by angiotensin receptors., (Copyright © 2019 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)- Published
- 2020
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