endothelin-1 and Coronary-Stenosis

Restenosis is a common and serious complication following angioplasty and stent implantation in patients with arterial vascular disease. Restenosis is a form of intimal hyperplasia. Endothelin-1 (ET-1) and vascular endothelial growth factor (VEGF) stimulate intimal hyperplasia and may play a role in restenosis. ET-1 and VEGF may act in concert in promoting restenosis following mechanical injury to the vessel wall in angioplasty and stent implantation. An understanding of their mechanism of action may lead to more effective methods for preventing restenosis. ET-1 receptor antagonists may play a prominent role in prophylaxis.

Topics: Angioplasty, Balloon, Coronary; Coronary Stenosis; Endothelial Growth Factors; Endothelin-1; Endothelium, Vascular; Humans; Primary Prevention; Prognosis; Risk Assessment; Secondary Prevention; Stents

Nitric oxide (NO) and endothelin-1 are potentially significant factors contributing to the pathogenesis of post-angioplasty restenosis. It may be postulated that low-level laser therapy (LLLT) can favorably influence the process of restenosis by affecting those factors.. The aim of the study was to evaluate the effect of LLLT applied during percutaneous coronary intervention (PCI) on the factors participating in the homeostasis of vascular tone - NO and endothelin-1.. In a randomized, prospective study of 52 subjects undergoing PCI, an additional 808 nm intravascular LLLT was applied at a dose of 9 J/cm2 in the lesion part. The control group was 49 subjects with PCI only. We assessed the concentration of nitrites/nitrates reflecting NO metabolism as well as endothelin-1 in both groups before PCI, and at 6 h, 12 h and 1 month after the procedure. In addition, half a year after PCI, a follow-up angiography was performed.. Statistically higher nitrite/nitrate concentrations were observed in the laser group as compared to the control group in all tests except the pre-PCI assays. Endothelin-1 levels were significantly higher in the laser group 6 h after PCI with a significant decrease in subsequent tests, which was not observed in the control group. The restenosis rate was 15.0% in the laser group and 32.4% in the control group (however the difference was not statistically significant).. LLLT applied during the PCI procedure can influence the process of restenosis by modifying NO and endothelin-1 concentrations.

Topics: Aged; Coronary Stenosis; Endothelin-1; Female; Humans; Low-Level Light Therapy; Male; Middle Aged; Nitric Oxide; Percutaneous Coronary Intervention; Prospective Studies

To investigate the usefulness of the plasma big endothelin-1 (big ET-1) level in predicting the severity of new-onset stable angiography-proven coronary artery disease (CAD).. A total of 963 consecutive stable CAD patients with more than 50% stenosis in at least one main vessel were enrolled. The patients were classified into the three groups according to the tertile of the Gensini score (GS, low GS ＜20, n=300; intermediate GS 20-40, n=356 and high GS ＞40, n=307), and the relationship between the big ET-1 level and GS was evaluated.. The plasma levels of big ET-1 increased significantly in association with increases in the GS tertile (p=0.007). A multivariate analysis suggested that the plasma big ET-1 level was an independent predictor for a high GS (OR=2.26, 95%CI: 1.23-4.15, p=0.009), and there was a positive correlation between the big ET-1 level and the GS (r=0.20, p=0.000). The area under the receiver operating characteristic curve (AUC) for the big ET-1 level in predicting a high GS was 0.64 (95% CI 0.60-0.68, p=0.000), and the optimal cutoff value for the plasma big ET-1 level for predicting a high GS was 0.34 fmol/mL, with a sensitivity of 62.6% and specificity of 60.3%. In the high-big ET-1 level group (≥0.34 fmol/mL), there were significantly increased rates of three-vessel disease (43.6% vs. 35.4%, p=0.017) and a high GS [31 (17-54) vs. 24 (16-44), p=0.001] compared with that observed in the low-big ET-1 level group.. The present findings indicate that the plasma big ET-1 level is a useful predictor of the severity of new-onset stable CAD associated with significant stenosis.

Topics: Age of Onset; Biomarkers; China; Cohort Studies; Coronary Angiography; Coronary Artery Disease; Coronary Stenosis; Endothelin-1; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prognosis; ROC Curve; Severity of Illness Index

Distal to a chronic coronary artery stenosis, structural remodeling of the microvasculature occurs. The microvascular functional changes distal to the stenosis have not been studied in detail. We tested the hypothesis that microvascular structural remodeling is accompanied by altered regulation of coronary vasomotor tone with increased responsiveness to endothelin-1. Vasomotor tone was studied in coronary microvessels from healthy control swine and from swine 3 to 4 months after implantation of an occluder that causes a progressive coronary narrowing, resulting in regional left ventricular dysfunction and blunted myocardial vasodilator reserve. Arterioles (approximately 200-microm passive inner diameter at 60 mm Hg) were isolated from regions perfused by the stenotic left anterior descending and normal left circumflex coronary arteries and studied in vitro. Passive pressure-diameter curves demonstrated reduced distensibility of subendocardial left anterior descending compared with subendocardial left circumflex or control arterioles, suggestive of structural remodeling. Myogenic responses were blunted in subendocardial left anterior descending compared with left circumflex arterioles, reflecting altered smooth muscle function. However, vasodilator responses to nitroprusside and bradykinin were not different in the endocardium, suggesting preserved endothelium and smooth muscle responsiveness. Finally, vasoconstrictor responses to endothelin-1 were enhanced in left anterior descending arterioles compared with left circumflex or control arterioles. Regional myocardial vascular conductance responses to bradykinin and endothelin in vivo confirmed the in vitro observations. In conclusion, inward remodeling of coronary microvessels distal to a stenosis is accompanied by exaggerated vasoconstrictor responses to endothelin-1. These structural and functional alterations may aggravate flow abnormalities distal to a chronic coronary artery stenosis.

Topics: Animals; Arterioles; Blood Pressure; Bradykinin; Coronary Circulation; Coronary Stenosis; Coronary Vessels; Disease Models, Animal; Dose-Response Relationship, Drug; Endothelin-1; Endothelium, Vascular; Female; Heart Rate; Male; Microcirculation; Nitroprusside; Swine; Vasoconstriction; Vasodilation; Vasodilator Agents