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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Cardioprotection conferred by sodium-glucose cotransporter 2 inhibitors: a renal proximal tubule perspective

Texto completo
dos Santos, Danubia Silva [1] ; Polidoro, Juliano Z. [1] ; Borges-Junior, Flavio A. [1] ; Girardi, Adriana C. C. [1]
Número total de Autores: 4
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Heart Inst InCor, Sao Paulo, SP - Brazil
Número total de Afiliações: 1
Tipo de documento: Artigo Científico
Citações Web of Science: 1

Sodium-glucose cotransporter 2 (SGLT2) inhibitors, also known as gliflozins, improve glycemia by suppressing glucose reuptake in the renal proximal tubule. Currently, SGLT2 inhibitors are primarily indicated as antidiabetic agents; however. their benefits extend far beyond glucose control. Cardiovascular outcome trials indicated that all studied SGLT2 inhibitors remarkably and consistently reduce cardiovascular mortality and hospitalization for heart failure (HF) in type 2 diabetes (T2D) patients. Nevertheless. the mechanisms underlying the unprecedented cardiovascular benefits of gliflozins remain elusive. Multiple processes that directly or indirectly improve myocardial performance may be involved, including the amelioration of proximal tubular dysfunction. Therefore. this paper provides a perspective on the potential cellular and molecular mechanisms of the proximal tubule that may, at least in part, mediate the cardioprotection conferred by SGLT2 inhibitors. Specifically, we focus on the effects of SGLT2 on extracellular volume homeostasis, including its plausible functional and physical association with the apical Na+/H+ exchanger isoform 3 as well as its complex and its possible bidirectional interactions with the intrarenal angiotensin system and renal sympathetic nervous system. We also discuss evidence supporting a potential benefit of gliflozins in reducing cardiovascular risk, attributable to their effect on proximal tubule handling of uric acid and albumin as well as in erythropoietin production. Unraveling the mechanisms behind the beneficial actions of SGLT2 inhibitors may not only contribute to a better understanding of the pathophysiology of cardiovascular diseases but also enable repurposing of gliflozins to improve the routine management of HF patients with or without T2D. (AU)

Processo FAPESP: 16/22140-7 - Bases moleculares da função e da disfunção tubular renal
Beneficiário:Adriana Castello Costa Girardi
Linha de fomento: Auxílio à Pesquisa - Temático