Endothelial dysfunction in Sickle Cell Disease: Strategies for the treatment

Autor(es)

Pavan, Aline Renata ; Terroni, Barbara ; Santos, Jean Leandro Dos

• Tipo de documento: Artigo Científico
• Fonte: NITRIC OXIDE-BIOLOGY AND CHEMISTRY; v. 149, p. 11-pg., 2024-05-31.

Resumo

Sickle Cell Anemia (SCA), is an inherited hemoglobinopathy characterized by the presence of an abnormal hemoglobin (HbS), being the most prevalent sickle cell disease (SCD). SCA is characterized by vascular endothelial dysfunction, which contributes significantly to various clinical conditions, including but not limited to pulmonary hypertension, priapism, cutaneous leg ulceration, and stroke. The pathophysiology of endothelial dysfunction (ED) in SCA is a multifaceted process involving a chronic inflammatory and hypercoagulable state. Key factors include hemolysis-associated elements like reduced arginine and nitric oxide (NO) availability, elevated levels of vascular adhesion molecules, the uncoupling effect of NO synthase, heightened arginase activity, an environment characterized by oxidative stress with the production of reactive oxygen and nitrogen species, and occurrences of ischemia-reperfusion injury, along with apolipoprotein A-1 depletion. The urgency for novel interventions addressing ED is evident. Presently, there is a focus on investigating small molecules that disrupt the arginine-nitric oxide pathway, exhibiting anti-inflammatory and antioxidant properties while diminishing levels of cellular and vascular adhesion molecules. In this mini -review article, we delve into the progress made in strategies for treating ED in SCD with the aim of cultivating insights for drug design. (AU)

• Processo FAPESP: 23/05739-6 - Estratégias para intervenção em complexos repressores do gene de gama-globina contendo Histona Deacetilase (HDAC-1 e HDAC-2)
• Beneficiário: Jean Leandro dos Santos
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/19523-7 - Planejamento, síntese e avaliação farmacológica de derivados de hidroxiuréia planejados como inibidores de histona deacetilase para Anemia Falciforme
• Beneficiário: Aline Renata Pavan
• Modalidade de apoio: Bolsas no Brasil - Doutorado