Correlation of serum VEGF-C, ANGPTL4, and activin A levels with frailty

Hung-Chen Chang; Xiaojun Wang; Xuchao Gu; Shuai Jiang; Wenhao Wang; Tao Wu; Maoqing Ye; Xinkai Qu; Zhijun Bao

doi:10.1016/j.exger.2023.112345

Correlation of serum VEGF-C, ANGPTL4, and activin A levels with frailty

Exp Gerontol. 2024 Jan:185:112345. doi: 10.1016/j.exger.2023.112345. Epub 2023 Dec 15.

Authors

Hung-Chen Chang¹, Xiaojun Wang², Xuchao Gu³, Shuai Jiang⁴, Wenhao Wang⁵, Tao Wu⁵, Maoqing Ye⁶, Xinkai Qu⁷, Zhijun Bao⁸

Affiliations

¹ Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China; Department of Cardiology, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China.
² Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China; Department of Gerontology, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China.
³ Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China; Department of Traditional Chinese Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China.
⁴ Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China; Department of Thoracic Surgery, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China.
⁵ Department of Traditional Chinese Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China.
⁶ Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China; Department of Cardiology, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China; Shanghai institute of geriatric medicine, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China. Electronic address: yemaoqing@fudan.edu.cn.
⁷ Department of Cardiology, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China. Electronic address: qxkchest@126.com.
⁸ Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China; Department of Gerontology, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China; Shanghai institute of geriatric medicine, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China. Electronic address: zhijunbao@fudan.edu.cn.

PMID: 38092160
DOI: 10.1016/j.exger.2023.112345

Abstract

Background: Secretory factors linked to lymphogenesis, such as vascular endothelial growth factor C (VEGF-C), angiopoietin like protein 4 (ANGPTL4), and activin A (ACV-A), have been recognized as potential markers of chronic inflammatory status and age-related diseases. Furthermore, these factors may also be linked to frailty. The primary objective of this study was to examine the serum VEGF-C, ANGPTL4, and ACV-A levels in young individuals, healthy older individuals, and older individuals with pre-frailty and frailty, and to determine their association with pro-inflammatory factor levels.

Methods: We conducted an observational study, enrolling a total of 210 older individuals and 20 young healthy volunteers. Participants were divided into four groups based on the Freid frailty phenotype: healthy young group, older patients without frailty group, pre-frail older group, and frail older group. Plasma and peripheral blood mononuclear cells (PBMCs) were collected from all four groups. ELISA was used to measure the serum levels of VEGF-C, ANGPTL4, ACV-A, and pro-inflammatory cytokines, while RT-qPCR was used to measure the transcription level of VEGF-C, ANGPTL4 and ACV-A in PBMCs.

Results: In comparison to healthy young individuals and older participants without frailty, older participants with frailty exhibited lower renal function, higher serum levels and transcription levels of VEGF-C, ANGPTL4, ACV-A, and elevated levels of pro-inflammatory cytokines (CRP, IL-1β, and TNF-α). Multiple linear regression analysis revealed that serum levels of VEGF-C, ANGPTL4, and ACV-A were positively correlated with the frailty index, independent of age, eGFR, and comorbidities. Furthermore, the receiver operating characteristic (ROC) curve analysis demonstrated that serum levels of VEGF-C, ANGPTL4, and ACV-A have great accuracy in predicting frailty.

Conclusion: Elevated serum levels of VEGF-C, ANGPTL4, and ACV-A are associated with frailty status.

Keywords: ANGPTL4; Activin a; Frailty; Pro-inflammatory cytokines; VEGF-C.

Publication types

Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Angiopoietin-Like Protein 4
Cytokines
Frailty*
Humans
Leukocytes, Mononuclear
Vascular Endothelial Growth Factor C*

Substances

activin A
Angiopoietin-Like Protein 4
ANGPTL4 protein, human
Cytokines
Vascular Endothelial Growth Factor C
VEGFC protein, human