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Thromb Haemost
DOI: 10.1055/a-2600-6318
Cellular Signaling and Proteolysis

CXCL2 Mediates Lactate Secretion and Promotes Aortic Dissection Formation through the p38/JNK/C-myc Pathways

Jiakang Li   *
1   Department of Cardiac Surgery, Fujian Medical University Union Hospital, Fuzhou, China
2   The Key Laboratory of Fujian Province Universities on Ion Channel and Signal Transduction in Cardiovascular Diseases, Department of Pathophysiology, The School of Basic Medical Sciences, Fuzhou, China
3   Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fujian Province University, Fuzhou, China
,
Zhihuang Qiu   *
1   Department of Cardiac Surgery, Fujian Medical University Union Hospital, Fuzhou, China
3   Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fujian Province University, Fuzhou, China
,
Rumei Xie
1   Department of Cardiac Surgery, Fujian Medical University Union Hospital, Fuzhou, China
2   The Key Laboratory of Fujian Province Universities on Ion Channel and Signal Transduction in Cardiovascular Diseases, Department of Pathophysiology, The School of Basic Medical Sciences, Fuzhou, China
3   Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fujian Province University, Fuzhou, China
,
Likang Ma
1   Department of Cardiac Surgery, Fujian Medical University Union Hospital, Fuzhou, China
3   Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fujian Province University, Fuzhou, China
,
Lele Tang
1   Department of Cardiac Surgery, Fujian Medical University Union Hospital, Fuzhou, China
3   Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fujian Province University, Fuzhou, China
,
Mengge Yao
1   Department of Cardiac Surgery, Fujian Medical University Union Hospital, Fuzhou, China
2   The Key Laboratory of Fujian Province Universities on Ion Channel and Signal Transduction in Cardiovascular Diseases, Department of Pathophysiology, The School of Basic Medical Sciences, Fuzhou, China
3   Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fujian Province University, Fuzhou, China
,
Zhaofeng Zhang
1   Department of Cardiac Surgery, Fujian Medical University Union Hospital, Fuzhou, China
3   Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fujian Province University, Fuzhou, China
,
Liangwan Chen
1   Department of Cardiac Surgery, Fujian Medical University Union Hospital, Fuzhou, China
3   Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fujian Province University, Fuzhou, China
,
Li Zhang 
1   Department of Cardiac Surgery, Fujian Medical University Union Hospital, Fuzhou, China
2   The Key Laboratory of Fujian Province Universities on Ion Channel and Signal Transduction in Cardiovascular Diseases, Department of Pathophysiology, The School of Basic Medical Sciences, Fuzhou, China
3   Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fujian Province University, Fuzhou, China
› Author Affiliations Funding This study was supported by the National Natural Science Foundation of China (U2005202, 82370470, 82241209).
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Abstract

Background

Aortic dissection (AD) is a critical cardiovascular condition with high mortality risk, and elevated lactate levels are linked to increased postoperative mortality in AD patients. CXCL2 is recognized for its significant involvement in cardiovascular pathologies. Nevertheless, the mechanisms by which CXCL2 regulates lactate levels in AD remain to be fully elucidated.

Methods

We assessed CXCL2, CXCR2, p38/JNK, C-myc, MCT1, and MCT4 expression using Western blotting, real-time PCR, and immunostaining on AD patient samples, mouse models, and human aortic vascular smooth muscle cells (HAVSMCs). Lactate levels were measured with a lactate assay kit, and we investigated CXCL2's role in AD through vessel incubation.

Results

CXCL2 and CXCR2 expression was significantly upregulated in AD, accompanied by increased lactate secretion. Overexpression of CXCL2 not only stimulated lactate secretion but also expedited AD progression. In contrast, CXCR2 inhibition effectively countered the effects of CXCL2. Furthermore, CXCL2 elevated the expression of MCT1 and MCT4; inhibition of them alleviated CXCL2-induced AD and lactate accumulation. CXCL2 also activated the p38 and JNK signaling pathways and upregulated C-myc expression, leading to enhanced lactate secretion in HAVSMCs. Blocking these pathways reversed the effects induced by CXCL2.

Conclusion

The CXCL2–CXCR2 axis regulated lactate secretion and drove the progression of AD through the activation of the p38/JNK/C-myc signaling pathways. These findings provide new insights into the molecular mechanisms underlying AD and identify potential therapeutic targets for clinical intervention.

Keywords

aortic dissection - CXCL2 - lactate - p38/JNK/C-myc

Authors' Contribution

J.L. contributed to writing—original draft. R.X., L.M., and L.T. contributed to data analysis. M.Y. and Z.Z. contributed to methodology. Z.Q. contributed to investigation. L.Z. and L.C. contributed to writing—review and editing.


* These authors contributed equally to this study.


Supplementary Material



Publication History

Received: 20 November 2024

Accepted: 05 May 2025

Article published online:
21 May 2025

© 2025. Thieme. All rights reserved.

Georg Thieme Verlag KG
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