CC BY-NC-ND 4.0 · Thromb Haemost 2021; 121(06): 741-754
DOI: 10.1055/s-0040-1721505
Endothelium and Angiogenesis

Endothelial β1 Integrin-Mediated Adaptation to Myocardial Ischemia

Carina Henning*
1  Institute of Metabolic Physiology, Department of Biology, Heinrich-Heine-University, Düsseldorf, Germany
,
Anna Branopolski*
1  Institute of Metabolic Physiology, Department of Biology, Heinrich-Heine-University, Düsseldorf, Germany
2  Division of Cardiology, Pulmonology, and Vascular Medicine, Heinrich-Heine-University, Düsseldorf, Germany
,
Paula Follert
1  Institute of Metabolic Physiology, Department of Biology, Heinrich-Heine-University, Düsseldorf, Germany
,
Oksana Lewandowska
1  Institute of Metabolic Physiology, Department of Biology, Heinrich-Heine-University, Düsseldorf, Germany
,
Aysel Ayhan
2  Division of Cardiology, Pulmonology, and Vascular Medicine, Heinrich-Heine-University, Düsseldorf, Germany
,
Marcel Benkhoff
2  Division of Cardiology, Pulmonology, and Vascular Medicine, Heinrich-Heine-University, Düsseldorf, Germany
,
Ulrich Flögel
3  Institute for Molecular Cardiology, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany
,
Malte Kelm
2  Division of Cardiology, Pulmonology, and Vascular Medicine, Heinrich-Heine-University, Düsseldorf, Germany
,
2  Division of Cardiology, Pulmonology, and Vascular Medicine, Heinrich-Heine-University, Düsseldorf, Germany
4  Department of Clinical and Experimental Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom
5  Surrey and Sussex Healthcare NHS Trust, Redhill, Surrey, United Kingdom
,
Eckhard Lammert*
1  Institute of Metabolic Physiology, Department of Biology, Heinrich-Heine-University, Düsseldorf, Germany
6  Institute for Vascular and Islet Cell Biology, German Diabetes Center (DDZ)—Leibniz Center for Diabetes Research, Düsseldorf, Germany
7  German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
› Author Affiliations
Funding This project was supported and funded by the Deutsche Forschungsgemeinschaft (DFG) through the SFB 1116 (“Master Switches in Cardiac Ischemia”), the SFB 974 (“Communication and Systems Relevance during Liver Damage and Regeneration”), the IRTG 1902 (“Intra- and Interorgan Communication of the Cardiovascular System”) and the Federal Ministry of Health, the Ministry of Culture and Science of North Rhine-Westphalia, and the German Center for Diabetes Research (DZD e.V.).

Abstract

Background Short episodes of myocardial ischemia can protect from myocardial infarction. However, the role of endothelial β1 integrin in these cardioprotective ischemic events is largely unknown.

Objective In this study we investigated whether endothelial β1 integrin is required for cardiac adaptation to ischemia and protection from myocardial infarction.

Methods Here we introduced transient and permanent left anterior descending artery (LAD) occlusions in mice. We inhibited β1 integrin by intravenous injection of function-blocking antibodies and tamoxifen-induced endothelial cell (EC)-specific deletion of Itgb1. Furthermore, human ITGB1 was silenced in primary human coronary artery ECs using small interfering RNA. We analyzed the numbers of proliferating ECs and arterioles by immunohistochemistry, determined infarct size by magnetic resonance imaging (MRI) and triphenyl tetrazolium chloride staining, and analyzed cardiac function by MRI and echocardiography.

Results Transient LAD occlusions were found to increase EC proliferation and arteriole formation in the entire myocardium. These effects required β1 integrin on ECs, except for arteriole formation in the ischemic part of the myocardium. Furthermore, this integrin subunit was also relevant for basal and mechanically induced proliferation of human coronary artery ECs. Notably, β1 integrin was needed for cardioprotection induced by transient LAD occlusions, and the absence of endothelial β1 integrin resulted in impaired growth of blood vessels into the infarcted myocardium and reduced cardiac function after permanent LAD occlusion.

Conclusion We showed that endothelial β1 integrin is required for adaptation of the heart to cardiac ischemia and protection from myocardial infarction.

* These authors contributed equally to this work.


Supplementary Material



Publication History

Received: 22 October 2020

Accepted: 28 October 2020

Publication Date:
14 January 2021 (online)

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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