Tß4-Ac-SDKP pathway: Any relevance for the cardiovascular system?
Can J Physiol Pharmacol
; 97(7): 589-599, 2019 Jul.
Article
em En
| MEDLINE
| ID: mdl-30854877
ABSTRACT
The last 20 years witnessed the emergence of the thymosin ß4 (Tß4)-N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) pathway as a new source of future therapeutic tools to treat cardiovascular and renal diseases. In this review article, we attempted to shed light on the numerous experimental findings pertaining to the many promising cardiovascular therapeutic avenues for Tß4 and (or) its N-terminal derivative, Ac-SDKP. Specifically, Ac-SDKP is endogenously produced from the 43-amino acid Tß4 by 2 successive enzymes, meprin α and prolyl oligopeptidase. We also discussed the possible mechanisms involved in the Tß4-Ac-SDKP-associated cardiovascular biological effects. In infarcted myocardium, Tß4 and Ac-SDKP facilitate cardiac repair after infarction by promoting endothelial cell migration and myocyte survival. Additionally, Tß4 and Ac-SDKP have antifibrotic and anti-inflammatory properties in the arteries, heart, lungs, and kidneys, and stimulate both in vitro and in vivo angiogenesis. The effects of Tß4 can be mediated directly through a putative receptor (Ku80) or via its enzymatically released N-terminal derivative Ac-SDKP. Despite the localization and characterization of Ac-SDKP binding sites in myocardium, more studies are needed to fully identify and clone Ac-SDKP receptors. It remains promising that Ac-SDKP or its degradation-resistant analogs could serve as new therapeutic tools to treat cardiac, vascular, and renal injury and dysfunction to be used alone or in combination with the already established pharmacotherapy for cardiovascular diseases.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oligopeptídeos
/
Timosina
/
Sistema Cardiovascular
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Can J Physiol Pharmacol
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos