From Stress to Sick(le) and Back Again–Oxidative/Antioxidant Mechanisms, Genetic Modulation, and Cerebrovascular Disease in Children with Sickle Cell Anemia

Silva, Marisa; Faustino, Paula

Publication

From Stress to Sick(le) and Back Again–Oxidative/Antioxidant Mechanisms, Genetic Modulation, and Cerebrovascular Disease in Children with Sickle Cell Anemia

2023-11-07Journal article

dc.contributor.author	Silva, Marisa
dc.contributor.author	Faustino, Paula
dc.date.accessioned	2024-02-19T11:56:09Z
dc.date.available	2024-02-19T11:56:09Z
dc.date.issued	2023-11-07
dc.description	(This article belongs to the Special Issue Genetics and Epigenetic Modifications on Metabolic Diseases Oxidative Related)	pt_PT
dc.description.abstract	Sickle cell anemia (SCA) is a genetic disease caused by the homozygosity of the HBB:c.20A>T mutation, which results in the production of hemoglobin S (HbS). In hypoxic conditions, HbS suffers autoxidation and polymerizes inside red blood cells, altering their morphology into a sickle shape, with increased rigidity and fragility. This triggers complex pathophysiological mechanisms, including inflammation, cell adhesion, oxidative stress, and vaso-occlusion, along with metabolic alterations and endocrine complications. SCA is phenotypically heterogeneous due to the modulation of both environmental and genetic factors. Pediatric cerebrovascular disease (CVD), namely ischemic stroke and silent cerebral infarctions, is one of the most impactful manifestations. In this review, we highlight the role of oxidative stress in the pathophysiology of pediatric CVD. Since oxidative stress is an interdependent mechanism in vasculopathy, occurring alongside (or as result of) endothelial dysfunction, cell adhesion, inflammation, chronic hemolysis, ischemia-reperfusion injury, and vaso-occlusion, a brief overview of the main mechanisms involved is included. Moreover, the genetic modulation of CVD in SCA is discussed. The knowledge of the intricate network of altered mechanisms in SCA, and how it is affected by different genetic factors, is fundamental for the identification of potential therapeutic targets, drug development, and patient-specific treatment alternatives.	pt_PT
dc.description.version	info:eu-repo/semantics/publishedVersion	pt_PT
dc.identifier.citation	Antioxidants (Basel). 2023 Nov 7;12(11):1977. doi: 10.3390/antiox12111977	pt_PT
dc.identifier.doi	10.3390/antiox12111977	pt_PT
dc.identifier.issn	2076-3921
dc.identifier.uri	http://hdl.handle.net/10400.18/9122
dc.language.iso	eng	pt_PT
dc.peerreviewed	yes	pt_PT
dc.publisher	MDPI	pt_PT
dc.relation.publisherversion	https://www.mdpi.com/2076-3921/12/11/1977	pt_PT
dc.rights.uri	http://creativecommons.org/licenses/by/4.0/	pt_PT
dc.subject	Sickle Cell Anemia	pt_PT
dc.subject	Cerebrovascular Disease	pt_PT
dc.subject	Antioxidant Mechanisms	pt_PT
dc.subject	Genetic Modulators	pt_PT
dc.subject	Oxidative Stress	pt_PT
dc.subject	Vasculopathy	pt_PT
dc.subject	Anemia	pt_PT
dc.subject	Stresse Oxidativo	pt_PT
dc.subject	Hemoglobinopatias	pt_PT
dc.subject	Drepanocitose	pt_PT
dc.subject	Vasculopatia Cerebral	pt_PT
dc.subject	Modificadores Genéticos	pt_PT
dc.subject	Doenças Raras	pt_PT
dc.subject	Doenças Genéticas	pt_PT
dc.title	From Stress to Sick(le) and Back Again–Oxidative/Antioxidant Mechanisms, Genetic Modulation, and Cerebrovascular Disease in Children with Sickle Cell Anemia	pt_PT
dc.type	journal article
dspace.entity.type	Publication
oaire.citation.issue	11	pt_PT
oaire.citation.startPage	1977	pt_PT
oaire.citation.title	Antioxidants	pt_PT
oaire.citation.volume	12	pt_PT
person.familyName	Faustino
person.givenName	Paula
person.identifier.ciencia-id	F01A-353A-433E
person.identifier.orcid	0000-0002-6269-4867
person.identifier.rid	M-3519-2014
person.identifier.scopus-author-id	8158641100
rcaap.embargofct	Acesso de acordo com política editorial da revista.	pt_PT
rcaap.rights	openAccess	pt_PT
rcaap.type	article	pt_PT
relation.isAuthorOfPublication	94303e78-8b7d-4e24-811d-3af3b1a4e330
relation.isAuthorOfPublication.latestForDiscovery	94303e78-8b7d-4e24-811d-3af3b1a4e330