Endothelial β1 Integrin-Mediated Adaptation to Myocardial Ischemia

Autor: Oksana Lewandowska, Aysel Ayhan, Malte Kelm, Eckhard Lammert, Marcel Benkhoff, Paula Follert, Christian Heiss, Carina Henning, Anna Branopolski, Ulrich Flögel
Rok vydání: 2021
Předmět:
Male
0301 basic medicine
Cardiac function curve
medicine.medical_specialty
Nitric Oxide Synthase Type III
Integrin
Myocardial Infarction
Ischemia
Neovascularization
Physiologic
030204 cardiovascular system & hematology
Young Adult
03 medical and health sciences
0302 clinical medicine
Arteriole
endothelial β1 integrin
Internal medicine
medicine.artery
Animals
Humans
Medicine
cardiovascular diseases
Myocardial infarction
Cell Proliferation
Mice
Knockout
Cardioprotection
biology
business.industry
Integrin beta1
Endothelial Cells
cardiac vascular growth
Hematology
medicine.disease
Coronary Vessels
Endothelium and Angiogenesis
Mice
Inbred C57BL
Endothelial stem cell
Disease Models
Animal
030104 developmental biology
medicine.anatomical_structure
cardioprotection
Ischemic Preconditioning
Myocardial
cardiovascular system
Cardiology
biology.protein
business
Signal Transduction
Artery
Zdroj: Thrombosis and Haemostasis
ISSN: 2567-689X
0340-6245
DOI: 10.1055/s-0040-1721505
Popis: 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.
Databáze: OpenAIRE
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