Endothelial PPARγ Is Crucial for Averting Age-Related Vascular Dysfunction by Stalling Oxidative Stress and ROCK

A Correction to this article was published on 27 May 2019

This article has been updated

Abstract

Aging plays a significant role in the progression of vascular diseases and vascular dysfunction. Activation of the ADP-ribosylation factor 6 and small GTPases by inflammatory signals may cause vascular permeability and endothelial leakage. Pro-inflammatory molecules have a significant effect on smooth muscle cells (SMC). The migration and proliferation of SMC can be promoted by tumor necrosis factor alpha (TNF-α). TNF-α can also increase oxidative stress in SMCs, which has been identified to persuade DNA damage resulting in apoptosis and cellular senescence. Peroxisome proliferator-activated receptor (PPAR) acts as a ligand-dependent transcription factor and a member of the nuclear receptor superfamily. They play key roles in a wide range of biological processes, including cell differentiation and proliferation, bone formation, cell metabolism, tissue remodeling, insulin sensitivity, and eicosanoid signaling. The PPARγ activation regulates inflammatory responses, which can exert protective effects in the vasculature. In addition, loss of function of PPARγ enhances cardiovascular events and atherosclerosis in the vascular endothelium. This appraisal, therefore, discusses the critical linkage of PPARγ in the inflammatory process and highlights a crucial defensive role for endothelial PPARγ in vascular dysfunction and disease, as well as therapy for vascular aging.

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Change history

  • 27 May 2019

    The original article unfortunately contains minor errors in Figs. 1 and 2. The correct Fig. 1 is shown below. The correct Fig. 2 is shown below.

Abbreviations

PPARγ:

peroxisome proliferator-activated receptor gamma

ROCK:

rho-kinase

ROS:

reactive oxygen species

eNOS:

endothelial nitric oxide synthase

PUFAs:

polyunsaturated fatty acids

TZDs:

thiazolidinediones

IBD:

inflammatory bowel disease.

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Acknowledgments

The authors are grateful to the Department of Pharmacy, Southeast University, Dhaka, Bangladesh.

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This work was carried out in collaboration between all authors. MSU and GMA designed the study, wrote the protocol, and managed the analyses of the study. MSU, MTK, MJ, GEB, and AAM prepared the draft of the manuscript. MSU prepared the figures of the manuscript. KN, MSA, and GEB reviewed the scientific contents of the manuscript. All authors read and approved the final submitted version of the manuscript.

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Correspondence to Md. Sahab Uddin or Ghulam Md Ashraf.

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Uddin, M.S., Kabir, M.T., Jakaria, M. et al. Endothelial PPARγ Is Crucial for Averting Age-Related Vascular Dysfunction by Stalling Oxidative Stress and ROCK. Neurotox Res 36, 583–601 (2019). https://doi.org/10.1007/s12640-019-00047-5

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Keywords

  • PPARγ
  • Inflammation
  • Aging
  • Vascular dysfunction
  • Oxidative stress
  • ROCK