Abstract
C-reactive protein (CRP) is an important predictor of cardiovascular events and plays a role in vascular inflammation and vessel damage. The aim of this study was to investigate the effect of pentameric CRP (pCRP) and monomeric CRP (mCRP) on the production of atherosclerosis-related factors in cultured human coronary artery endothelial cells (HCAECs). HCAECs were treated with pCRP, mCRP, p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580, or transfected with p38 MAPK siRNA. Western blotting was performed to detect the expression of vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), intercellular adhesion molecule-2 (ICAM-2) and vascular cell adhesion molecule-1 (VCAM-1). Proliferation, damage, and apoptosis of HCAECs were examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, lactate dehydrogenase (LDH), and flow cytometry, respectively. mCRP suppressed VEGF and COX-2 expression and enhanced ICAM-2 and VCAM-1 expression in HCAECs, in both dose-dependent and time-dependent manner. Except at 100 µg/ml concentration and 20-hour or 24-hour incubation, pCRP had no apparent effects. mCRP but not pCRP induced HCAEC injury and phosphorylation of p38 MAPK, and the inhibitor SB203580 reversed the effects of mCRP. mCRP promotes injury and apoptosis of HCAECs through a p38 MAPK-dependent mechanism, which provides a new therapy for the injury of HCAECs in atherosclerosis.
Highlights
At present cardiovascular disease has become the most common cause of death worldwide
We found that monomeric CRP (mCRP) mediates p38 mitogen-activated protein kinase (p38MAPK)-dependent expression of vascular endothelial growth factor (VEGF), COX-2, intercellular adhesion molecule-2 (ICAM-2), and vascular cell adhesion molecule-1 (VCAM-1) protein in human coronary artery endothelial cells (HCAECs), and this affects HCAECs injury
These findings reveal that p38 mitogen-activated protein kinase (MAPK) is a new mechanism for C-reactive protein (CRP)-mediated HCAECs dysfunction, which may be a potential target for vascular disease
Summary
At present cardiovascular disease has become the most common cause of death worldwide. The main contributing factor of cardiac death is atherosclerosis, which is defined as a chronic inflammatory disease in the arterial wall [1]. Atherosclerosis is exacerbated by certain cardiovascular risk factors, such as inflammatory response, elevated basal levels of cytokines, hypertension, diabetes, and obesity, of which inflammation plays an important role in plaque development and precipitation of clinical symptoms [2,3]. Atherosclerosis in its early stages is usually asymptomatic due to plaques forming over a prolonged period of time [4]. The atherosclerosis event is as an initial manifestation of the disease, including acute coronary diseases, myocardial infarction, and stroke [5,6,7]
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