Role of purinergic signalling in endothelial dysfunction and thrombo-inflammation in ischaemic stroke and cerebral small vessel disease

Lee, Natasha Ting and Ong, Lin Kooi and Gyawali, Prajwal ORCID: https://orcid.org/0000-0003-0975-5576 and Che Mohd Nassir, Che Mohd Nasril and Mustapha, Muzaimi and Nandurkar, Harshal H. and Sashindranath, Maithili (2021) Role of purinergic signalling in endothelial dysfunction and thrombo-inflammation in ischaemic stroke and cerebral small vessel disease. Biomolecules, 11 (7):994.

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Abstract

The cerebral endothelium is an active interface between blood and the central nervous system. In addition to being a physical barrier between the blood and the brain, the endothelium also actively regulates metabolic homeostasis, vascular tone and permeability, coagulation, and movement of immune cells. Being part of the blood–brain barrier, endothelial cells of the brain have specialized morphology, physiology, and phenotypes due to their unique microenvironment. Known cardiovascular risk factors facilitate cerebral endothelial dysfunction, leading to impaired vasodilation, an aggravated inflammatory response, as well as increased oxidative stress and vascular proliferation. This culminates in the thrombo-inflammatory response, an underlying cause of ischemic stroke and cerebral small vessel disease (CSVD). These events are further exacerbated when blood flow is returned to the brain after a period of ischemia, a phenomenon termed ischemia-reperfusion injury. Purinergic signaling is an endogenous molecular pathway in which the enzymes CD39 and CD73 catabolize extracellular adenosine triphosphate (eATP) to adenosine. After ischemia and CSVD, eATP is released from dying neurons as a damage molecule, triggering thrombosis and inflammation. In contrast, adenosine is anti-thrombotic, protects against oxidative stress, and suppresses the immune response. Evidently, therapies that promote adenosine generation or boost CD39 activity at the site of endothelial injury have promising benefits in the context of atherothrombotic stroke and can be extended to current CSVD known pathomechanisms. Here, we have reviewed the rationale and benefits of CD39 and CD39 therapies to treat endothelial dysfunction in the brain.


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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Faculty/School / Institute/Centre: Current - Faculty of Health, Engineering and Sciences - School of Health and Wellbeing (1 Jan 2015 -)
Faculty/School / Institute/Centre: Current - Faculty of Health, Engineering and Sciences - School of Health and Wellbeing (1 Jan 2015 -)
Date Deposited: 09 Jul 2021 03:14
Last Modified: 27 Oct 2021 01:32
Uncontrolled Keywords: CD39; endothelial dysfunction; brain; stroke; endothelial cells; purinergic signaling
Fields of Research (2008): 11 Medical and Health Sciences > 1109 Neurosciences > 110904 Neurology and Neuromuscular Diseases
11 Medical and Health Sciences > 1102 Cardiovascular Medicine and Haematology > 110299 Cardiovascular Medicine and Haematology not elsewhere classified
11 Medical and Health Sciences > 1102 Cardiovascular Medicine and Haematology > 110201 Cardiology (incl. Cardiovascular Diseases)
Fields of Research (2020): 32 BIOMEDICAL AND CLINICAL SCIENCES > 3201 Cardiovascular medicine and haematology > 320101 Cardiology (incl. cardiovascular diseases)
32 BIOMEDICAL AND CLINICAL SCIENCES > 3201 Cardiovascular medicine and haematology > 320199 Cardiovascular medicine and haematology not elsewhere classified
Socio-Economic Objectives (2008): C Society > 92 Health > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases
C Society > 92 Health > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920111 Nervous System and Disorders
Socio-Economic Objectives (2020): 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280103 Expanding knowledge in the biomedical and clinical sciences
Identification Number or DOI: https://doi.org/10.3390/biom11070994
URI: http://eprints.usq.edu.au/id/eprint/42647

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