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From Stress to Sick(le) and Back Again–Oxidative/Antioxidant Mechanisms, Genetic Modulation, and Cerebrovascular Disease in Children with Sickle Cell Anemia
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Autores
Orientador(es)
Resumo(s)
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.
Descrição
(This article belongs to the Special Issue Genetics and Epigenetic Modifications on Metabolic Diseases Oxidative Related)
Palavras-chave
Sickle Cell Anemia Cerebrovascular Disease Antioxidant Mechanisms Genetic Modulators Oxidative Stress Vasculopathy Anemia Stresse Oxidativo Hemoglobinopatias Drepanocitose Vasculopatia Cerebral Modificadores Genéticos Doenças Raras Doenças Genéticas
Contexto Educativo
Citação
Antioxidants (Basel). 2023 Nov 7;12(11):1977. doi: 10.3390/antiox12111977
Editora
MDPI