Impact of the Renin–Angiotensin System on the Endothelium in Vascular Dementia: Unresolved Issues and Future Perspectives

Noureddine, Fatima Y; Altara, Raffaele; Fan, Fan; Yabluchanskiy, Andriy; Booz, George W.; Zouein, Fouad A.

doi:10.3390/ijms21124268

Cited by 18 publications

(25 citation statements)

References 78 publications

(134 reference statements)

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“…Increasing amounts of evidence indicate that Ang II plays an important role in the initiation and progression of vascular endothelial dysfunction, inflammation and vascular remodelling [ 31 ]. Ang II–induced effects of hypertension on retinal vessels lead to vascular changes, including intimal hyperplasia, hyaline degeneration, endothelial cell barrier dysfunction and breakdown of the blood–retina barrier (BRB), which promote exudation of serum proteins and lipids into the retina, leading to fluid accumulation (oedema) in multiple layers of the retina [ [32] , [33] , [34] ].…”

Section: Discussionmentioning

confidence: 99%

CXCL1-CXCR2 signalling mediates hypertensive retinopathy by inducing macrophage infiltration

et al. 2022

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Section: Discussionmentioning

confidence: 99%

CXCL1-CXCR2 signalling mediates hypertensive retinopathy by inducing macrophage infiltration

et al. 2022

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“…The effects of the RAS dysregulation surpass the renal and cardiovascular systems to encompass other body tissues and organs, including the brain (Noureddine et al, 2020). Thus, it has been reported that SARS-CoV-2-infected patients can have a significant functional impairment of RAS (Osman et al, 2021;Wang et al, 2022a), which is a consequence of the binding of SARS-CoV-2' RBD of the viral S protein, precisely, the S1 subunit to the ACE2 enzyme in human cells.…”

Section: Systemic Renin-angiotensin System and Covid-19-associated Ne...mentioning

confidence: 99%

Role of the renin-angiotensin system in the development of COVID-19-associated neurological manifestations

Méndez-García

Escobedo

Minguer-Uribe

et al. 2022

Front. Cell. Neurosci.

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SARS-CoV-2 causes COVID-19, which has claimed millions of lives. This virus can infect various cells and tissues, including the brain, for which numerous neurological symptoms have been reported, ranging from mild and nonlife-threatening (e.g., headaches, anosmia, dysgeusia, and disorientation) to severe and life-threatening symptoms (e.g., meningitis, ischemic stroke, and cerebral thrombosis). The cellular receptor for SARS-CoV-2 is angiotensinconverting enzyme 2 (ACE2), an enzyme that belongs to the renin-angiotensin system (RAS). RAS is an endocrine system that has been classically associated with regulating blood pressure and fluid and electrolyte balance; however, it is also involved in promoting inflammation, proliferation, fibrogenesis, and lipogenesis. Two pathways constitute the RAS with counter-balancing effects, which is the key to its regulation. The first axis (classical) is composed of angiotensin-converting enzyme (ACE), angiotensin (Ang) II, and angiotensin type 1 receptor (AT1R) as the main effector, which -when activated-increases the production of aldosterone and antidiuretic hormone, sympathetic nervous system tone, blood pressure, vasoconstriction, fibrosis, inflammation, and reactive oxygen species (ROS) production. Both systemic and local classical RAS' within the brain are associated with cognitive impairment, cell death, and inflammation. The second axis (non-classical or alternative) includes ACE2, which converts Ang II to Ang-(1-7), a peptide molecule that activates Mas receptor (MasR) in charge of opposing Ang II/AT1R actions. Thus, the alternative RAS axis enhances cognition, synaptic remodeling, cell survival, cell signal transmission, and antioxidant/anti-inflammatory mechanisms in the brain. In a physiological state, both RAS axes remain balanced. However, some Frontiers in Cellular Neuroscience 01 frontiersin.org Méndez-García et al. 10.3389/fncel.2022.977039factors can dysregulate systemic and local RAS arms. The binding of SARS-CoV-2 to ACE2 causes the internalization and degradation of this enzyme, reducing its activity, and disrupting the balance of systemic and local RAS, which partially explain the appearance of some of the neurological symptoms associated with COVID-19. Therefore, this review aims to analyze the role of RAS in the development of the neurological effects due to SARS-CoV-2 infection. Moreover, we will discuss the RAS-molecular targets that could be used for therapeutic purposes to treat the short and long-term neurological COVID-19-related sequelae.

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“…Mechanistically, endothelial cells, smooth muscle cells, glial cells, and neurons all utilize ACE2 for proper function [41] in many brain regions [43]. Consequently, brain levels of ACE2 are relevant for the degree of ischemic injury and its subsequent potential impact on neurodegeneration, Alzheimer’s disease (AD), and dementia risk [43-45]. ACE2 levels are accordingly inversely correlated with parenchymal amyloid beta and tau in AD [46].…”

Section: Sars-cov-2 General Infection Characteristicsmentioning

confidence: 99%

The Impact of the COVID-19 Pandemic on Dementia Risk: Potential Pathways to Cognitive Decline

Pyne¹,

Brickman²

2021

Neurodegener Dis

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Background: Coronavirus disease 2019 (COVID-19), the far-reaching pandemic, has infected approximately 185 million of the world’s population to date. After infection, certain groups, including older adults, men, and people of color, are more likely to have adverse medical outcomes. COVID-19 can affect multiple organ systems, even among asymptomatic/mild severity individuals, with progressively worse damage for those with higher severity infections. Summary: The COVID-19 virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily attaches to cells through the angiotensin-converting enzyme 2 (ACE2) receptor, a universal receptor present in most major organ systems. As SARS-CoV-2 binds to the ACE2 receptor, its bioavailability becomes limited, thus disrupting homeostatic organ function and inducing an injury cascade. Organ damage can then arise from multiple sources including direct cellular infection, overactive detrimental systemic immune response, and ischemia/hypoxia through thromboembolisms or disruption of perfusion. In the brain, SARS-CoV-2 has neuroinvasive and neurotropic characteristics with acute and chronic neurovirulent potential. In the cardiovascular system, COVID-19 can induce myocardial and systemic vascular damage along with thrombosis. Other organ systems such as the lungs, kidney, and liver are all at risk for infection damage. Key Messages: Our hypothesis is that each injury consequence has the independent potential to contribute to long-term cognitive deficits with the possibility of progressing to or worsening pre-existing dementia. Already, reports from recovered COVID-19 patients indicate that cognitive alterations and long-term symptoms are prevalent. This critical review highlights the injury pathways possible through SARS-CoV-2 infection that have the potential to increase and contribute to cognitive impairment and dementia.

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Impact of the Renin–Angiotensin System on the Endothelium in Vascular Dementia: Unresolved Issues and Future Perspectives

Cited by 18 publications

References 78 publications

CXCL1-CXCR2 signalling mediates hypertensive retinopathy by inducing macrophage infiltration

CXCL1-CXCR2 signalling mediates hypertensive retinopathy by inducing macrophage infiltration

Role of the renin-angiotensin system in the development of COVID-19-associated neurological manifestations

The Impact of the COVID-19 Pandemic on Dementia Risk: Potential Pathways to Cognitive Decline

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