Endothelial Krüppel-like factor 2/4: Regulation and function in cardiovascular diseases

Jing Gao; Hongjie Pan; Xiaogang Guo; Yu Huang; Jiang-Yun Luo

doi:10.1016/j.cellsig.2025.111699

Endothelial Krüppel-like factor 2/4: Regulation and function in cardiovascular diseases

Jing Gao
, Hongjie Pan
, Xiaogang Guo
, Yu Huang^*
, Jiang-Yun Luo^*

^*Corresponding author for this work

Department of Biomedical Sciences

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

15 Citations (Scopus)

Abstract

This review presents an overview of the regulation, function, disease-relevance and pharmacological regulation of the critical endothelial transcription factors KLF2/4 in vasculature. The regulatory mechanisms of KLF2/4 expression and activity in vascular endothelium in response to hemodynamic forces and biochemical stimuli are depicted. The functional effects mediated by direct or indirect target genes of KLF2/4 in endothelial cells are systematically summarized. The contributory roles that dysregulated KLF2/4 play in relevant cardiovascular pathologies, such as atherosclerotic vascular lesions, pulmonary arterial hypertension and vascular complications of diabetes were reviewed. Moreover, this review also discusses the pharmacological regulation of KLF2/4 by drugs used in clinics and therapeutic possibility by directly targeting these two transcription factors for treating atherosclerotic cardiovascular diseases. Finally, prospective opinions on the gaps in disclosing novel vascular function mediated by KLF2/4 and future research needs are expressed. © 2025 Elsevier Inc.

Original language	English
Article number	111699
Journal	Cellular Signalling
Volume	130
Online published	27 Feb 2025
DOIs	https://doi.org/10.1016/j.cellsig.2025.111699
Publication status	Published - Jun 2025

Funding

This work is supported by Grants from Shanghai Pujiang Program (22PJ1410200), National Natural Science Foundation of China (82322009, 32241016, 82000251), and Research Grants Council of Hong Kong (T12-101/23-N and SRFS2021-4S04).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Keywords

Atherosclerosis
Endothelial cells
Krüppel-like factor 2
Krüppel-like factor 4
Vascular diseases

RGC Funding Information

RGC-funded

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10.1016/j.cellsig.2025.111699

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Check CityUHK Library

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Cite this

@article{c4c184d403624f47b137f169e88b517e,

title = "Endothelial Kr{\"u}ppel-like factor 2/4: Regulation and function in cardiovascular diseases",

abstract = "This review presents an overview of the regulation, function, disease-relevance and pharmacological regulation of the critical endothelial transcription factors KLF2/4 in vasculature. The regulatory mechanisms of KLF2/4 expression and activity in vascular endothelium in response to hemodynamic forces and biochemical stimuli are depicted. The functional effects mediated by direct or indirect target genes of KLF2/4 in endothelial cells are systematically summarized. The contributory roles that dysregulated KLF2/4 play in relevant cardiovascular pathologies, such as atherosclerotic vascular lesions, pulmonary arterial hypertension and vascular complications of diabetes were reviewed. Moreover, this review also discusses the pharmacological regulation of KLF2/4 by drugs used in clinics and therapeutic possibility by directly targeting these two transcription factors for treating atherosclerotic cardiovascular diseases. Finally, prospective opinions on the gaps in disclosing novel vascular function mediated by KLF2/4 and future research needs are expressed. {\textcopyright} 2025 Elsevier Inc.",

keywords = "Atherosclerosis, Endothelial cells, Kr{\"u}ppel-like factor 2, Kr{\"u}ppel-like factor 4, Vascular diseases",

author = "Jing Gao and Hongjie Pan and Xiaogang Guo and Yu Huang and Jiang-Yun Luo",

year = "2025",

month = jun,

doi = "10.1016/j.cellsig.2025.111699",

language = "English",

volume = "130",

journal = "Cellular Signalling",

issn = "0898-6568",

publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Endothelial Krüppel-like factor 2/4

T2 - Regulation and function in cardiovascular diseases

AU - Gao, Jing

AU - Pan, Hongjie

AU - Guo, Xiaogang

AU - Huang, Yu

AU - Luo, Jiang-Yun

PY - 2025/6

Y1 - 2025/6

N2 - This review presents an overview of the regulation, function, disease-relevance and pharmacological regulation of the critical endothelial transcription factors KLF2/4 in vasculature. The regulatory mechanisms of KLF2/4 expression and activity in vascular endothelium in response to hemodynamic forces and biochemical stimuli are depicted. The functional effects mediated by direct or indirect target genes of KLF2/4 in endothelial cells are systematically summarized. The contributory roles that dysregulated KLF2/4 play in relevant cardiovascular pathologies, such as atherosclerotic vascular lesions, pulmonary arterial hypertension and vascular complications of diabetes were reviewed. Moreover, this review also discusses the pharmacological regulation of KLF2/4 by drugs used in clinics and therapeutic possibility by directly targeting these two transcription factors for treating atherosclerotic cardiovascular diseases. Finally, prospective opinions on the gaps in disclosing novel vascular function mediated by KLF2/4 and future research needs are expressed. © 2025 Elsevier Inc.

AB - This review presents an overview of the regulation, function, disease-relevance and pharmacological regulation of the critical endothelial transcription factors KLF2/4 in vasculature. The regulatory mechanisms of KLF2/4 expression and activity in vascular endothelium in response to hemodynamic forces and biochemical stimuli are depicted. The functional effects mediated by direct or indirect target genes of KLF2/4 in endothelial cells are systematically summarized. The contributory roles that dysregulated KLF2/4 play in relevant cardiovascular pathologies, such as atherosclerotic vascular lesions, pulmonary arterial hypertension and vascular complications of diabetes were reviewed. Moreover, this review also discusses the pharmacological regulation of KLF2/4 by drugs used in clinics and therapeutic possibility by directly targeting these two transcription factors for treating atherosclerotic cardiovascular diseases. Finally, prospective opinions on the gaps in disclosing novel vascular function mediated by KLF2/4 and future research needs are expressed. © 2025 Elsevier Inc.

KW - Atherosclerosis

KW - Endothelial cells

KW - Krüppel-like factor 2

KW - Krüppel-like factor 4

KW - Vascular diseases

UR - https://www.scopus.com/pages/publications/85219045639

UR - https://www.scopus.com/pages/publications/85219045639#tab=impact

U2 - 10.1016/j.cellsig.2025.111699

DO - 10.1016/j.cellsig.2025.111699

M3 - RGC 21 - Publication in refereed journal

SN - 0898-6568

VL - 130

JO - Cellular Signalling

JF - Cellular Signalling

M1 - 111699

ER -

Endothelial Krüppel-like factor 2/4: Regulation and function in cardiovascular diseases

Abstract

Funding

UN SDGs

Research Keywords

RGC Funding Information

Access Output

Other Access Options

Permanent Link

Other Files and Links

Fingerprint

TBRS: Single-Cell Multi-Omics Study of Atherosclerotic Vascular Disease: Narrowing the Gap Between Bench and Bedside

SRFS: Systemic Benefits of Physical Activity: Crosstalk between Organs on Signal Transduction from Mechano-stimulation to Metabolism

Cite this

Endothelial Krüppel-like factor 2/4: Regulation and function in cardiovascular diseases

Abstract

Funding

UN SDGs

Research Keywords

RGC Funding Information

Access Output

Other Access Options

Permanent Link

Other Files and Links

Fingerprint

Projects

TBRS: Single-Cell Multi-Omics Study of Atherosclerotic Vascular Disease: Narrowing the Gap Between Bench and Bedside

SRFS: Systemic Benefits of Physical Activity: Crosstalk between Organs on Signal Transduction from Mechano-stimulation to Metabolism

Cite this