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Global Translational Medicine

ORIGINAL RESEARCH ARTICLE
The vasculoprotective effects of resveratrol are

mediated via Kruppel-like factor 2 dependent
protection of endothelial barrier function

4†
Xianming Zhou 1,2† , Lily Lin , and Hong Shi 1,3,4 *
1 Case Cardiovascular Research Institute, Case Western Reserve University School of Medicine,
Cleveland, OH, USA
2 Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong
University of Science and Technology, Wuhan, China
3 Division of Rheumatology, Medical College of Georgia at Augusta University, Augusta, GA,
USA
4 Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, GA, USA

Abstract
Resveratrol is a naturally occurring polyphenolic compound that is thought to
have vasculoprotective properties. Its observed effects are proposed, in part, to
be mediated through the induction of endothelial Krϋppel-like factor 2 (KLF2)
expression. KLF2 is a nuclear transcription factor that is highly expressed within
the vascular endothelium. Studies from our laboratory and others have shown that
† These authors contributed equally this protein mediates vascular function through its transactivation domain, and its
to this work. targeted expression promotes vascular health, notably by acting as an important
*Corresponding author: positive regulator of endothelial barrier function. In this study, we demonstrate
Hong Shi that resveratrol possesses endothelial barrier protective effects dependent on the
(hoshi@augusta.edu) presence of KLF2, with several key endothelial tight junction proteins expressed in
Citation: Zhou X, Lin L, Shi H, a KLF2-dependent manner. Collectively, our findings identify KLF2 as essential for
2023, The vasculoprotective resveratrol-mediated endothelial barrier protection, thus further implicating KLF2 as
effects of resveratrol are mediated a critical vasculoprotective factor.
via Kruppel-like factor 2 dependent
protection of endothelial barrier
function. Global Transl Med, 2(1):
218. Keywords: Resveratrol; Krϋppel-like factor 2; Barrier function
https://doi.org/10.36922/gtm.v2i1.218
Received: October 11, 2022
Accepted: November 24, 2022
Published Online: January 10, 1. Introduction
2023
Resveratrol (3,5,4′-trihydroxy-trans-stilbene), a polyphenol that is notably present at
Copyright: © 2023 Author(s).
This is an Open Access article high concentrations in grapes and red wine, is occasionally used as a dietary supplement,
distributed under the terms of the although its beneficial effects remain unproven. It has generated a significant amount of
Creative Commons Attribution clinical interest for its many beneficial effects on multiple pathologic processes, including
License, permitting distribution,
and reproduction in any medium, hypertension, diabetic cardiomyopathy, atherosclerosis, heart failure, and several types
provided the original work is of cancer [1,2] . Studies performed in rodent models have added to a growing body of
properly cited. evidence that suggests the presence of resveratrol which is vasculoprotective. Resveratrol
Publisher’s Note: AccScience has been shown to improve endothelial dysfunction and decrease vascular inflammation,
Publishing remains neutral with resulting in reduced ischemic damage in vital organs [2-4] . Recently, resveratrol has been
regard to jurisdictional claims in identified as having protective effects on endothelial barrier function in the vasculature
published maps and institutional
affiliations. of the brain and retina [5,6] . However, the detailed molecular mechanisms by which

Volume 2 Issue 1 (2023) 1 https://doi.org/10.36922/gtm.v2i1.218