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Published on: January 28, 2020
Serum cyclin-dependent kinase 9 is a potential biomarker of atherosclerotic inflammation
Yeming Han1, Shanshan Zhao2, Yaoqin Gong2,3
1Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Department of of Cardiology, Qilu Hospital, Shandong University, Jinan, Shandong, 250012, China.
Insights
Cyclin-dependent kinase 9 (CDK9) is elevated in patients with atherosclerotic coronary artery disease (CAD). This protein plays a key role in inflammation, suggesting CDK9 as a potential biomarker and therapeutic target for CAD.
Area of Science:
- Cardiovascular Medicine
- Molecular Biology
- Immunology
Background:
- Coronary artery disease (CAD) is a leading global health concern, with atherosclerosis being its primary driver.
- Understanding the molecular mechanisms of atherosclerosis is crucial for developing effective treatments.
Purpose of the Study:
- To identify novel protein biomarkers associated with atherosclerotic inflammation in CAD patients.
- To investigate the role of Cyclin-dependent kinase 9 (CDK9) in the pathogenesis of atherosclerosis.
Main Methods:
- Proteomic analysis using two-dimensional gel electrophoresis and mass spectrometry to profile serum proteins in CAD patients.
- Analysis of CDK9 expression in serum, monocytes, and artery plaque samples.
- Assessment of CD14+ monocyte/macrophage infiltration in artery plaques.
- In vitro studies using Flavopiridol (a CDK9 inhibitor) to evaluate its effect on THP-1 cell proliferation.
Main Results:
- A distinct serum protein expression pattern was identified in CAD patients.
- CDK9 was significantly elevated in the serum, monocytes, and artery plaques of CAD patients.
- Elevated CDK9 expression correlated with increased infiltration of CD14+ monocytes/macrophages in atherosclerotic plaques.
- Flavopiridol effectively inhibited THP-1 cell proliferation by targeting CDK9.
Conclusions:
- CDK9 plays a significant role in the inflammatory processes underlying atherosclerosis.
- CDK9 may serve as a potential biomarker for atherosclerotic inflammation.
- Targeting CDK9 offers a potential therapeutic strategy for atherosclerotic CAD.
Abstract:
Atherosclerotic coronary artery disease (CAD) is one of the most prevalent diseases worldwide. Atherosclerosis was considered to be the single most important contributor to CAD. In this study, a distinct serum protein expression pattern in CAD patients was demonstrated by proteomic analysis with two-dimensional gel electrophoresis coupled with mass spectrometry. In particular, CDK9 was found to be highly elevated in serum, monocytes and artery plaque samples of CAD patients. Furthermore, there was high infiltration of CD14+ monocytes/macrophages within artery plaques correlated with the expression of CDK9. Moreover, Flavopiridol (CDK9 inhibitor) could inhibit THP-1 cell (monocytic acute leukemia cell line) proliferation by targeting CDK9. Altogether, These findings indicate that CDK9 represent an important role for inflammation in the pathogenesis of atherosclerosis. It may be a potential biomarker of atherosclerotic inflammation and offer insights into the pathophysiology and targeted therapy for atherosclerotic CAD.
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