CCL4 contributes to aging related angiogenic insufficiency through activating oxidative stress and endothelial inflammation

Ting-Ting Chang; Liang-Yu Lin; Ching Chen; Jaw-Wen Chen

doi:10.1007/s10456-024-09922-y

CCL4 contributes to aging related angiogenic insufficiency through activating oxidative stress and endothelial inflammation

Angiogenesis. 2024 May 13. doi: 10.1007/s10456-024-09922-y. Online ahead of print.

Authors

Ting-Ting Chang^{1

2

3

4

5}, Liang-Yu Lin^{6

7}, Ching Chen^{8

6}, Jaw-Wen Chen^{9

10

11

12

13

14

15}

Affiliations

¹ Department and Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei, Taiwan. tf0619@nycu.edu.tw.
² School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. tf0619@nycu.edu.tw.
³ Biomedical Industry Ph.D. Program, National Yang Ming Chiao Tung University, Taipei, Taiwan. tf0619@nycu.edu.tw.
⁴ Cardiovascular Research Center, Taipei Medical University Hospital and Taipei Medical University, Taipei, Taiwan. tf0619@nycu.edu.tw.
⁵ Department and Institute of Pharmacology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. tf0619@nycu.edu.tw.
⁶ School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
⁷ Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
⁸ Department and Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei, Taiwan.
⁹ Department and Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei, Taiwan. iwchen99@gmail.com.
¹⁰ School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. iwchen99@gmail.com.
¹¹ Cardiovascular Research Center, Taipei Medical University Hospital and Taipei Medical University, Taipei, Taiwan. iwchen99@gmail.com.
¹² Division of Cardiology, Department of Medicine, Department of Research, Taipei Medical University Hospital, Taipei, Taiwan. iwchen99@gmail.com.
¹³ Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. iwchen99@gmail.com.
¹⁴ Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan. iwchen99@gmail.com.
¹⁵ Department of Research, Taipei Medical University Hospital, Taipei, Taiwan. iwchen99@gmail.com.

PMID: 38739303
DOI: 10.1007/s10456-024-09922-y

Abstract

Aging is a natural process associated with chronic inflammation in the development of vascular dysfunction. We hypothesized that chemokine C-C motif ligands 4 (CCL4) might play a vital role in aging-related vascular dysfunction. Circulating CCL4 was up-regulated in elderly subjects and in aged animals. CCL4 inhibition reduced generation of reactive oxygen species (ROS), attenuated inflammation, and restored cell functions in endothelial progenitor cells from elderly subjects and in aged human aortic endothelial cells. CCL4 promoted cell aging, with impaired cell functioning, by activating ROS production and inflammation. CCL4 knockout mice and therapeutic administration of anti-CCL4 neutralizing antibodies exhibited vascular and dermal anti-aging effects, with improved wound healing, via the down-regulation of inflammatory proteins and the activation of angiogenic proteins. Altogether, our findings suggested that CCL4 may contribute to aging-related vascular dysfunction via activating oxidative stress and endothelial inflammation. CCL4 may be a potential therapeutic target for vascular protections during aging.

Keywords: Aging; CCL4; Inflammation; Oxidative stress; Vascular dysfunction.

Abstract

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