Impact of the renin–angiotensin system on the endothelium in vascular dementia: Unresolved issues and future perspectives
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Multidisciplinary Digital Publishing Institute (MDPI)
Abstract
The effects of the renin–angiotensin system (RAS) surpass the renal and cardiovascular systems to encompass other body tissues and organs, including the brain. Angiotensin II (Ang II), the most potent mediator of RAS in the brain, contributes to vascular dementia via different mechanisms, including neuronal homeostasis disruption, vascular remodeling, and endothelial dysfunction caused by increased inflammation and oxidative stress. Other RAS components of emerging significance at the level of the blood–brain barrier include angiotensin-converting enzyme 2 (ACE2), Ang(1–7), and the AT2, Mas, and AT4 receptors. The various angiotensin hormones perform complex actions on brain endothelial cells and pericytes through specific receptors that have either detrimental or beneficial actions. Increasing evidence indicates that the ACE2/Ang(1–7)/Mas axis constitutes a protective arm of RAS on the blood–brain barrier. This review provides an update of studies assessing the different effects of angiotensins on cerebral endothelial cells. The involved signaling pathways are presented and help highlight the potential pharmacological targets for the management of cognitive and behavioral dysfunctions associated with vascular dementia. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
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Ace1, Ace2, Ang(1–7), At2 receptor, Blood–brain barrier, Mas receptor, Animals, Blood-brain barrier, Dementia, vascular, Gene expression regulation, Humans, Renin-angiotensin system, Signal transduction, Aminopeptidase, Amyloid precursor protein, Angiotensin 1 receptor, Angiotensin 2 receptor, Angiotensin 4 receptor, Angiotensin converting enzyme 2, Angiotensin ii, Carboxypeptidase, Cyclooxygenase 1, Cyclooxygenase 2, Deoxycorticosterone acetate, Dipeptidyl carboxypeptidase, Elastin, Endothelium derived hyperpolarizing factor, Immunoglobulin enhancer binding protein, Interleukin 1, Mammalian target of rapamycin, Membrane metalloendopeptidase, Mineralocorticoid receptor, Nitric oxide, Nitric oxide synthase, Peroxisome proliferator activated receptor alpha, Peroxisome proliferator activated receptor gamma, Phosphatidylinositol 3 kinase, Prostaglandin synthase, Reactive oxygen metabolite, Reduced nicotinamide adenine dinucleotide phosphate oxidase 2, Streptozocin, Unclassified drug, Unindexed drug, Vasculotropin, Akt/mtor signaling, Alzheimer disease, Angiogenesis, Apoptosis, Arterial stiffness, Astrocytosis, Atherosclerosis, Behavior disorder, Blood brain barrier, Blood vessel tone, Brain hemorrhage, Brain pericyte, Cardiovascular system, Carotid artery, Cell growth, Chronic kidney failure, Cognition, Cognitive defect, Dna damage, Endothelial dysfunction, Gene expression, Heart failure, Heart output, Homeostasis, Human, Hypertension, Inflammation, Middle cerebral artery occlusion, Mouse, Multiinfarct dementia, Nonhuman, Oxidative stress, Pi3k/akt signaling, Renin angiotensin aldosterone system, Review, Tight junction, Vascular remodeling, Vasodilatation, Animal, Metabolism