ACE2 in Brain Physiology and Pathophysiology: Evidence from Transgenic Animal Models

Alenina, Natalia; Bäder, Michael

doi:10.1007/s11064-018-2679-4

Cited by 125 publications

(123 citation statements)

References 87 publications

(105 reference statements)

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“…In addition, loss of ACE2 in brain cardiovascular centers short of neuronal death may impair proper autonomic nervous system regulation of blood pressure and potentially respiration (52). The loss of ACE2 in the brain stem may facilitate an increase in sympathetic drive, alterations in the baroreflex, and exacerbation of hypertension (1,8,54). Reduced expression of ACE2 in the vasculature may also promote endothelial dysfunction and inflammation and exacerbate existing atherosclerosis and diabetes (9,34,42,45,56,59).…”

mentioning

confidence: 99%

COVID-19, ACE2, and the cardiovascular consequences

South

Diz

Chappell

2020

American Journal of Physiology-Heart and Circulatory Physiology

685

721

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The novel SARS coronavirus SARS-CoV-2 pandemic may be particularly deleterious to patients with underlying cardiovascular disease (CVD). The mechanism for SARS-CoV-2 infection is the requisite binding of the virus to the membrane-bound form of angiotensin-converting enzyme 2 (ACE2) and internalization of the complex by the host cell. Recognition that ACE2 is the coreceptor for the coronavirus has prompted new therapeutic approaches to block the enzyme or reduce its expression to prevent the cellular entry and SARS-CoV-2 infection in tissues that express ACE2 including lung, heart, kidney, brain, and gut. ACE2, however, is a key enzymatic component of the renin-angiotensin-aldosterone system (RAAS); ACE2 degrades ANG II, a peptide with multiple actions that promote CVD, and generates Ang-(1-7), which antagonizes the effects of ANG II. Moreover, experimental evidence suggests that RAAS blockade by ACE inhibitors, ANG II type 1 receptor antagonists, and mineralocorticoid antagonists, as well as statins, enhance ACE2 which, in part, contributes to the benefit of these regimens. In lieu of the fact that many older patients with hypertension or other CVDs are routinely treated with RAAS blockers and statins, new clinical concerns have developed regarding whether these patients are at greater risk for SARS-CoV-2 infection, whether RAAS and statin therapy should be discontinued, and the potential consequences of RAAS blockade to COVID-19-related pathologies such as acute and chronic respiratory disease. The current perspective critically examines the evidence for ACE2 regulation by RAAS blockade and statins, the cardiovascular benefits of ACE2, and whether ACE2 blockade is a viable approach to attenuate COVID-19.

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mentioning

confidence: 99%

COVID-19, ACE2, and the cardiovascular consequences

South

Diz

Chappell

2020

American Journal of Physiology-Heart and Circulatory Physiology

685

721

View full text Add to dashboard Cite

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“…SARS-CoV-2 can invade the cardio-cerebrovascular system and damage the nervous system, which has been reported in several articles [8][9][10][11][12][13][14]. Angiotensin converting enzyme 2(ACE2) is highly expressed in human tissues such as vascular endothelial cells, heart, liver, digestive tract, and kidneys [15][16]. Studies have found that ACE2 is an important target for SARS-CoV-2 infection in humans.…”

Section: Discussionmentioning

confidence: 99%

“…On February 18, the patient had a high fever with a body temperature of 39.6℃, Re-examination of the craniocerebral CT revealed that: post craniocerebral operation, intracranial gas was accumulated, a drainage tube was placed, part of the left frontal parietal temporal bone was missing, and the left temporal lobe, basal ganglia and radiative coronal area showed patchy high-density lesions, which were significantly reduced compared with the previous (2020- [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]. The center line structure was less offset to the right than before, highdensity shadows on both sides of the ventricle were slightly reduced compared to before.…”

Section: Case Reportsmentioning

confidence: 91%

Clinical Features of COVID‐19 in a Young Man with Massive Cerebral Hemorrhage: Case Report

Bao

Lin

Cheng

et al. 2020

Preprint

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COVID-19 is currently a pandemic in the world, can invade multiple systems, and has a high morbidity and mortality. So far, no cases of acute cerebrovascular disease have been reported. This article reports the clinical features of a COVID-19 patient whose first symptom was cerebral hemorrhage. More importantly, after the craniotomy, the patient had high fever and it was difficult to retreat. After cerebrospinal fluid testing, it was determined that an intracranial infection had occurred. After anti-infection and plasma infusion of the recovered person, the patient's symptoms gradually improved. This case suggests that COVID-19 may infringe on cerebral blood vessels and cause cerebral hemorrhage. Transfusion of plasma from rehabilitation patients is effective for critically ill patients.

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“…We could detect Cltrn transcripts in brain (Figure c) and this is in line with the already described expression of ACE2 in the nervous system (Komatsu et al, ). ACE2 is a protein consisting of two domains; the N‐terminus is a carboxypeptidase homologous to angiotensin‐converting enzyme (ACE) and the C‐terminus is homologous to collectrin (Alenina & Bader, ). Additionally, CLTRN has been found in secretory vesicles and in proximity to vesicle/membrane fusion events in pancreatic β cells (Akpinar et al, ), and it binds to soluble N‐ethylmaleimide‐sensitive‐factor attachment protein receptor (SNARE), a protein complex involved in intracellular movement of vesicles and membrane proteins.…”

Section: Discussionmentioning

confidence: 99%

Loss of CLTRN function produces a neuropsychiatric disorder and a biochemical phenotype that mimics Hartnup disease

Pillai

Yubero

Shayota

et al. 2019

American J of Med Genetics Pt A

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Hartnup disease is an autosomal recessive condition characterized by neutral aminoaciduria and behavioral problems. It is caused by a loss of B 0 AT1, a neutral amino acid transporter in the kidney and intestine. CLTRN encodes the protein collectrin that functions in the transportation and activation of B 0 AT1 in the renal apical brush bordered epithelium. Collectrin deficient mice have severe aminoaciduria. However, the phenotype associated with collectrin deficiency in humans has not been reported.Here we report two patients, an 11-year-old male who is hemizygous for a small, interstitial deletion on Xp22.2 that encompasses CLTRN and a 22-year-old male with a deletion spanning exons 1 to 3 of CLTRN. Both of them present with neuropsychiatric phenotypes including autistic features, anxiety, depression, compulsions, and motor tics, as well as neutral aminoaciduria leading to a clinical diagnosis of Hartnup disease and treatment with niacin supplementation. Plasma amino acids were normal in both patients. One patient had low 5-hydroxyindoleacetic acid levels, a serotoninergic metabolite. We explored the expression of collectrin in the murine brain and found it to be particularly abundant in the hippocampus, brainstem, and cerebellum.We propose that collectrin deficiency in humans can be associated with aminoaciduria and a clinical picture similar to that seen in Hartnup disease. Further studies are needed to explore the role of collectrin deficiency in the neurological phenotypes. Nishitha R. Pillai and Delia Yubero shared joint first authorship.

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ACE2 in Brain Physiology and Pathophysiology: Evidence from Transgenic Animal Models

Cited by 125 publications

References 87 publications

COVID-19, ACE2, and the cardiovascular consequences

COVID-19, ACE2, and the cardiovascular consequences

Clinical Features of COVID‐19 in a Young Man with Massive Cerebral Hemorrhage: Case Report

Loss of CLTRN function produces a neuropsychiatric disorder and a biochemical phenotype that mimics Hartnup disease

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