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Updated: Jun 18, 2025

On-Chip Endothelial Inflammatory Phenotyping
Published on: July 21, 2012
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.
Background:
HCC-1 (hemofiltrate CC chemokine-1), a CC-type chemokine, exerts function to change intracellular calcium concentration, induce leukocyte, and manipulate enzyme release especially in monocytes. It has been reported that HCC-1 can predict the persistent acute kidney injury or suppress hepatocellular carcinoma by modulating cell cycle and promoting apoptosis; however, the effect of HCC-1 on atherosclerosis is poorly understood. Here, we aimed to clarify the function and mechanism of HCC-1 in atherosclerosis and whether it could serve as a novel biomarker for the diagnosis of atherosclerosis.
Methods:
HCC-1 expression in serum, atherosclerotic plaques, and normal arterial tissue from patients with atherosclerosis and control group was assessed by ELISA, immunohistochemistry and confocal microscope, and bioinformatic analysis. The atherosclerotic model of HCC-1 overexpressing and control mice was generated by tail vein injection of adeno-associated virus serotype 9-HCC-1 on an ApoE-/- background. Cell adhesion, polarization, and pyroptosis were evaluated in vitro. The relationship between HCC-1 concentration in serum and atherosclerosis was analyzed in patients with atherosclerosis.
Results:
HCC-1 expression was positively correlated with the occurrence and stable-unstable switch of atherosclerosis under bioinformatic analysis, which is further supported by the results of increased HCC-1 expression in atherosclerosis patients both in serum and atherosclerotic plaque. adeno-associated virus serotype 9-HCC-1 mice had higher levels of inflammatory factors, increased macrophage accumulation and pyroptotic rate in plaque, and decreased atherosclerotic plaque stability. In vitro, HCC-1 promoted monocyte adhesion and M1 polarization and induced inflammation and pyroptosis both in endothelial cells and macrophages.
Conclusions:
HCC-1 expression was increased in patients with atherosclerosis, and HCC-1 overexpression accelerated atherosclerotic burden via an enhancement in monocyte recruitment, M1 polarization, and pyroptosis both in endothelial cells and macrophages. Our findings suggested that HCC-1 may serve as an early biomarker for the diagnosis of atherosclerosis, with the capacity to reflect the degree of stenosis.
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