Dichloroacetate mitigates experimental abdominal aortic aneurysm via suppression of CXCL5-mediated neutrophil chemotaxis.

Authors

Zhen Wu, You-Fei Qi, Zi-Xin Deng, Xi Hu, Jin Kuang, Jie Yue, Hai-Yang Wang, Qing Wang

Published in

Biochimica et biophysica acta. Molecular basis of disease. Pages 168487. Sep 29, 2026. Epub Sep 29, 2026.

Abstract

Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease with high rupture-associated mortality. Current management relies on surgical or endovascular repair, with no effective pharmacological therapy. Inflammation and immune cell infiltration are central to AAA pathogenesis, but the molecular mechanisms remain incompletely defined.
Human AAA tissues and murine AAA models (CaCl₂ and porcine pancreatic elastase) were analyzed for chemokine expression and immune cell infiltration. The role of CXCL5 was investigated using immunohistochemistry, RNA-seq, and flow cytometry. The pharmacological effects of dichloroacetate (DCA), a pyruvate dehydrogenase kinase inhibitor, were assessed in vitro in smooth muscle cells and in vivo in AAA models.
CXCL5 was markedly enriched in human AAA lesions and associated with neutrophil infiltration. In murine AAA, neutrophil accumulation was evident and correlated with CXCL5 expression. DCA treatment suppressed ROS generation and NF-κB activation in smooth muscle cells, thereby reducing CXCL5 expression. Functionally, DCA significantly attenuated AAA formation in both CaCl₂- and elastase-induced models. Mechanistically, DCA mitigated AAA progression by inhibiting CXCL5-mediated neutrophil chemotaxis.
CXCL5-driven neutrophil recruitment is a key mechanism in AAA pathogenesis. DCA suppresses CXCL5 expression through inhibition of oxidative stress and NF-κB signaling, conferring protection against experimental AAA. These findings highlight CXCL5 as a potential therapeutic target and establish DCA as a promising candidate drug for AAA treatment.

PMID:
42810417
Bibliographic data and abstract were imported from PubMed on 30 Sep 2026.

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