Abstract
Growth-related oncogene-α (GRO-α) is a member of the CXC chemokine family, which is involved in the inflammatory process including atherosclerosis. We hypothesized that GRO-α may affect endothelial functions in both porcine coronary arteries and human coronary artery endothelial cells (HCAECs). Vasomotor function was analyzed in response to thromboxane A2 analog U-46619 for contraction, bradykinin for endothelium-dependent vasorelaxation, and sodium nitroprusside (SNP) for endothelium-independent vasorelaxation. In response to 10-6 M bradykinin, GRO-α (50 and 100 ng/ml) significantly reduced endothelium-dependent vasorelaxation by 34.73 and 48.8%, respectively, compared with controls (P < 0.05). There were no changes in response to U-46619 or SNP between treated and control groups. With the lucigenin-enhanced chemiluminescence assay, superoxide anion production in GRO-α-treated vessels (50 and 100 ng/ml) was significantly increased by 50 and 86%, respectively, compared with controls (P < 0.05). With real-time PCR analysis, endothelial nitric oxide synthase (eNOS) mRNA levels in porcine coronary arteries and HCAECs after GRO-α treatment were significantly decreased compared with controls (P < 0.05). The eNOS protein levels by both immunohistochemistry and Western blot analyses were also decreased in GRO-α-treated vessels. Antioxidant seleno-L-methionine and anti-GRO-α antibody effectively blocked these effects of GRO-α on both porcine coronary arteries and HCAECs. In addition, GRO-α immunoreactivity was substantially increased in the atherosclerotic regions compared with nonatherosclerotic regions in human coronary arteries. Thus GRO-α impairs endothelium-dependent vasorelaxation in porcine coronary arteries through a mechanism of overproduction of superoxide anion and downregulation of eNOS. GRO-α may contribute to human coronary artery disease.
Original language | English (US) |
---|---|
Pages (from-to) | H3088-H3095 |
Journal | American Journal of Physiology - Heart and Circulatory Physiology |
Volume | 293 |
Issue number | 5 |
DOIs | |
State | Published - Nov 2007 |
Keywords
- Antioxidant
- Atherosclerosis
- Chemokine
- Coronary artery
- Endothelial dysfunction
- Seleno-L-methionine
- Superoxide anion
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine
- Physiology (medical)