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Tissue kallikrein is related to the severity of coronary artery disease
Yu-yu Yao1, Cong Fu, Gen-shan Ma
1Department of Cardiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu 210009, China. yaoyuyunj@hotmail.com
Insights
Elevated tissue kallikrein (KLK1) levels predict coronary artery disease (CAD) presence and severity. Higher KLK1 indicates greater CAD extent and risk of major adverse cardiovascular events (MACE) in ACS patients.
Area of Science:
- Cardiovascular Research
- Biochemistry
- Pathophysiology
Background:
- The tissue kallikrein (KLK1)-kinin system (KKS) plays a role in atheroma development.
- The correlation between KKS and coronary artery disease (CAD) requires further investigation.
Purpose of the Study:
- To investigate the association between plasma KLK1 levels and the presence, severity, and outcomes of CAD.
- To explore the role of KLK1 in the pathophysiology of coronary plaques.
Main Methods:
- Measured plasma KLK1, VEGF, and hs-CRP in 100 CAD patients and 33 controls.
- Followed patients for major adverse cardiovascular events (MACE).
- Assessed KLK1 gene expression and protein localization in coronary endarterectomy specimens.
Main Results:
- CAD and acute coronary syndrome (ACS) patients exhibited significantly elevated KLK1 plasma levels.
- Plasma KLK1 strongly correlated with CAD severity and independently predicted CAD presence.
- KLK1 levels correlated with MACE in ACS patients and were elevated in unstable plaques, co-localizing with macrophages.
Conclusions:
- Plasma KLK1 levels are a valuable predictor for the presence and extent of CAD.
- Further extensive studies are needed to validate these findings and their clinical implications.
Background:
The impairment of the tissue kallikrein (KLK1)-kinin system (KKS) may result in atheroma development. However, it remains unclear if the KKS correlates with coronary artery disease (CAD).
Methods:
KLK1, VEGF and hs-CRP plasma levels were measured in 100 patients newly diagnosed with CAD and 33 CAD-free controls. Patients were followed-up for the incidence of major adverse cardiovascular events (MACE) for 8months to 2y. Gene expression of KLK1, CD105 and CD68 was assessed in human coronary endarterectomy specimens.
Results:
Patients with CAD and acute coronary syndrome (ACS) had significantly elevated KLK1 levels. In addition, the concentration of hs-CRP was increased in ACS patients. A strong positive correlation between plasma KLK1 and the severity of CAD was also demonstrated, suggesting that high KLK1 levels are an independent predictor for CAD. MACE during follow-up significantly correlated with KLK1 levels in the ACS group. Unstable coronary plaques demonstrated markedly increased KLK1 levels, macrophage infiltration and high microvessel density. Additionally, KLK1 staining primarily colocalized with macrophages.
Conclusions:
In the present study, plasma KLK1 levels were a useful predictor for the presence and extent of CAD. More extensive studies are, however, necessary in order to validate these findings.
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