Modulation of integrin receptor by polyphenols: Downstream Nrf2-Keap1/ARE and associated cross-talk mediators in cardiovascular diseases

Abstract

As a group of heterodimeric and transmembrane glycoproteins, integrin receptors are widely expressed in various cell types overall the body. During cardiovascular dysfunction, integrin receptors apply inhibitory effects on the antioxidative pathways, including nuclear factor erythroid 2–related factor 2 (Nrf2)-Kelch like ECH Associated Protein 1 (Keap1)/antioxidant response element (ARE) and interconnected mediators. As such, dysregulation in integrin signaling pathways influences several aspects of cardiovascular diseases (CVDs) such as heart failure, arrhythmia, angina, hypertension, hyperlipidemia, platelet aggregation and coagulation. So, modulation of integrin pathway could trigger the downstream antioxidant pathways toward cardioprotection. Regarding the involvement of multiple aforementioned mediators in the pathogenesis of CVDs, as well as the side effects of conventional drugs, seeking for novel alternative drugs is of great importance. Accordingly, the plant kingdom could pave the road in the treatment of CVDs. Of natural entities, polyphenols are multi-target and accessible phytochemicals with promising potency and low levels of toxicity. The present study aims at providing the cardioprotective roles of integrin receptors and downstream antioxidant pathways in heart failure, arrhythmia, angina, hypertension, hyperlipidemia, platelet aggregation and coagulation. The potential role of polyphenols has been also revealed in targeting the aforementioned dysregulated signaling mediators in those CVDs.

Keywords:

• Integrin
• polyphenol
• cardiovascular diseases
• Nrf2
• oxidative stress
• signaling pathway

Authors’ contributions

Conceptualization, S.F., and H.K.; software, S.F.; writing-original draft, S.F., S.Z.M., and Z.N.; review and editing, S.F., H.K., H.C. and J.X.

Disclosure statement

Nothing to be declared.

Funding

This study was supported by MICINN supporting the Ramón y Cajal grant for Jianbo Xiao (RYC2020-030365-I). The iranian authors acknowledged the Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, for the unique Grant No. 4000048.