CMX_SEMINAR（神戸大学CMX創発医学講演会）
Biomarkers of endothelial dysfunction＜内皮機能不全のバイオマーカー＞

Speaker: Prof. Maria Walczak「血管内皮機能」を大きなテーマとしてその機能不全に着目、 医薬品開発過程における候補物質の安全性評価において考慮されるべきことについて、臨床薬理学スペシャリストが最新の知見をご紹介下さいます。

日時： 2022. 12. 6（火） 16:00-17:20
オンライン開催

ZOOM URL：https://kobe-u-ac-jp.zoom.us/j/89101334465?pwd=YzFnekNybS83cnlEcUlvQ3c2cTdoUT09
ミーティングID: 891 0133 4465
パスコード: 675516

Abstract:
The strategic position of endothelium infers its indispensable role in controlling many biological processes, such as
regulation of vascular tone, haemostasis and inflammation. A healthy endothelium is essential for the undisturbed
functioning of the cardiovascular system, while an endothelial dysfunction is involved in the pathophysiology ofmultiple human diseases including atherothrombosis, diabetes, heart failure, sepsis, pulmonary hypertension,
microangiopathies of neurodegenerative diseases, liver steatosis and cancer metastasis. As confirmed by numerous
studies, the dysfunction of endothelium is either the cause or/and the effect of various diseases. Functional
alterations of numerous endothelial mediators and mechanisms may contribute to the pathologies associated withthe endothelial dysfunction. These include the loss of glycocalyx integrity, impairment of the production ofvasoprotective mediators, activation of pro-thrombotic, anti-fibrynolytic and pro-inflammatory mechanisms. Taking
into consideration the endothelium complexity, and the heterogeneous alterations of endothelial mediators invarious diseases, we suspect that the simultaneous quantification of multiple biomarkers might enable a better
insight into pathophysiology of the endothelial dysfunction and can provide a useful tool to stratify the risk as wellas to monitor the efficacy of endothelium-oriented therapy. Many drugs used today have an impact on theendothelial function, and their therapeutic efficacy is linked to the endothelial function improvement. Altogether,evidence have accumulated that a significant number of drugs are withdrawn years or decades after being in themarket. Endothelial toxicity might be the offender of the cardiovascular adverse effects observed for a significant
number of drugs. In this regard, endothelium-dependent side effects should be taken into account in the safetyassessment of a new drug candidate during the development process.
References:
1. Walczak M, Suraj J, Kus K, Kij A, Zakrzewska A, Chlopicki S: Towards a comprehensive endothelial biomarkers profiling and endotheliumguided pharmacotherapy. Pharmacol Rep. 2015 Aug;67(4):771-7. doi: 10.1016/j.pharep.2015.06.008.
2. Kurpińska A, Suraj J, Bonar E, Zakrzewska A, Stojak M, Sternak M, Jasztal A, Walczak M: Proteomic characterization of early lung response tobreast cancer metastasis in mice. Exp Mol Pathol. 2019 Apr;107:129-140. doi: 10.1016/j.yexmp.2019.02.001.
3. Suraj J, Kurpińska A, Sternak M, Smolik M, Niedzielska-Andres E, Zakrzewska A, Sacha T, Kania A, Chlopicki S, Walczak M. Quantitative
measurement of selected protein biomarkers of endothelial dysfunction in plasma by micro-liquid chromatography-tandem mass spectrometry
based on stable isotope dilution method. Talanta. 2019 Mar 1;194:1005-1016. doi: 10.1016/j.talanta.2018.10.067.
4. Suraj J, Kurpińska A, Zakrzewska A, Sternak M, Stojak M, Jasztal A, Walczak M, Chlopicki S: Early and late endothelial response in breast cancer
metastasis in mice: simultaneous quantification of endothelial biomarkers using a mass spectrometry-based method. Dis Model Mech. 2019 Mar
1;12(3):dmm036269. doi: 10.1242/dmm.036269
5. Matyjaszczyk-Gwarda K, Kij A, Olkowicz M, Fels B, Kusche-Vihrog K, Walczak M. Chlopicki S: Simultaneous quantification of selected
glycosaminoglycans by butanolysis-based derivatization and LC-SRM/MS analysis for assessing glycocalyx disruption in vitro and in vivo. Talanta.
2022 Feb 1;238(Pt 1):123008. doi: 10.1016/j.talanta.2021.123008.

Introducing the speaker (Self-introduction):
Maria Walczak has graduated at the Faculty of Pharmacy, Medical Academy in Krakow (Poland).
She received her PhD degree and habilitation at the Faculty of Pharmacy, Jagiellonian University
Medical College (UJ CM). Currently she is a head of the Chair and Department of Toxicology at theFaculty of Pharmacy UJ CM and a group leader at the Jagiellonian Centre for Experimental
Therapeutics (JCET, UJ). Her research primaly focuses on the pharmacokinetic and toxicokinetic
studies of bioactive compounds, metabolite identification, assessment of drug protein binding subsequently crucial for drug development. At the core of her work stands the bioanalysis ofbiomarkers related to civilisation deseases, as prognostic and diagnostic targets using mass
spectrometry-based methods. She is a specialist in clinical pharmacy.

Coordinator: 教授・島扶美（担当：創薬科学 内線：6582）
Organizer:メディカルトランスフォーメーション研究センター
Contact: 研究支援課研究企画係
E-mail: k9shien@med.kobe-u.ac.jp（内線:5195/5189 ）