HCC-1 Accelerates Atherosclerosis by Inducing Endothelial Cell and Macrophage Pyroptosis and Serves as an Early

Fan Bu1, Junhui Wang2, Juanjiang Chen1

  • 1Center for Clinical Laboratory, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China (F.B., J.C., Y. Hua, M.H., Y.L., Q.W.).

Insights

Hemofiltrate CC chemokine-1 (HCC-1) promotes atherosclerosis by increasing inflammation and cell death. Elevated HCC-1 levels in patients may indicate atherosclerosis and its severity, suggesting its potential as a diagnostic biomarker.

Area of Science:

  • Cardiovascular Biology
  • Immunology
  • Biochemistry

Background:

  • Hemofiltrate CC chemokine-1 (HCC-1) is a CC-type chemokine involved in immune responses.
  • While HCC-1's roles in kidney injury and cancer are known, its function in atherosclerosis is unclear.
  • This study investigates HCC-1's mechanism and diagnostic potential in atherosclerosis.

Purpose of the Study:

  • To elucidate the role of HCC-1 in the pathogenesis of atherosclerosis.
  • To determine if HCC-1 can serve as a novel biomarker for atherosclerosis diagnosis.
  • To explore the underlying molecular mechanisms of HCC-1's action in atherosclerosis.

Main Methods:

  • Assessed HCC-1 expression in patient serum and atherosclerotic plaques using ELISA and immunohistochemistry.
  • Generated an atherosclerotic mouse model with HCC-1 overexpression via AAV9.
  • Evaluated in vitro effects of HCC-1 on monocyte adhesion, polarization, and pyroptosis in endothelial cells and macrophages.

Main Results:

  • HCC-1 expression positively correlated with atherosclerosis occurrence and plaque instability.
  • HCC-1 overexpression in mice led to increased inflammation, macrophage accumulation, and pyroptosis, reducing plaque stability.
  • In vitro, HCC-1 promoted monocyte adhesion, M1 polarization, and induced inflammation and pyroptosis.

Conclusions:

  • Increased HCC-1 expression in atherosclerosis patients contributes to disease progression.
  • HCC-1 accelerates atherosclerosis by enhancing monocyte recruitment, M1 polarization, and pyroptosis.
  • HCC-1 shows potential as an early diagnostic biomarker for atherosclerosis, reflecting stenosis severity.
Abstract