Granty a projekty

Solubilní endoglin jako rizikovy faktor estrogeny-indukované cholestázy?

Soluble endoglin (sEng) is an important biomarker of various cardiovascular pathologies and moreover, it is involved in the pathogenesis of preeclampsia. Preeclampsia and intrahepatic cholestasis are serious complications of pregnancy, which threaten mothers and fetuses with adverse outcomes such as preterm delivery, or stillbirth. Clinical studies demonstrated strong co-incidence of both pathologies but the cause of this simultaneous worsening of especially liver functions is unknown. Our preliminary experiments have shown that sEng, may alter liver homeostasis of bile acids, the pivotal mediators of cholestasis in pregnancy. The aim of this project is therefore to determine the role of high sEng plasma levels in the pathophysiology of intrahepatic cholestasis. We will also study the role of labetalol, an alpha-/beta-adrenergic receptor antagonist that is recommended in the therapy of hypertension in pregnancy. To accomplish these goals, molecular analyses of plasma, bile, stool, and tissues will be performed in transgenic mice with high levels of sEng and cholestasis induced by ethinylestradiol. This grant proposal should elucidate new mechanistic insight into pathology of two serious complications of pregnancy and into corresponding effect of labetalol. Our results may create basis for future research in clinical practice that enables optimization of diagnostics and therapy of both diseases.

Číslo: GAUK1166119

Období: 01.01.2019 - 31.12.2021

Poskytovatel: Univerzita Karlova - Grantová agentura UK

Hlavní řešitel: Igreja e Sá Ivone Cristina, M.Sc. - Farmaceutická fakulta v Hradci Králové

Celkový objem financí: 857 000,00 Kč

Interní řešitelé

Hlavní řešitel: Ivone Cristina Igreja e Sá, M.Sc. - Farmaceutická fakulta v Hradci Králové, FaF HK
Spoluřešitel: PharmDr. Eva Doleželová, Ph.D. - Univerzita Karlova,
Spoluřešitel: Mgr. Katarína Tripská - Farmaceutická fakulta v Hradci Králové, FaF HK
Školitel: prof. PharmDr. Petr Nachtigal, Ph.D. - Univerzita Karlova,

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