endothelin-1 and Coronary-Vessel-Anomalies

Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndromes (ACS) afflicting predominantly younger to middle-aged women. Observational studies have reported a high prevalence of extracoronary vascular anomalies, especially fibromuscular dysplasia (FMD) and a low prevalence of coincidental cases of atherosclerosis. PHACTR1/EDN1 is a genetic risk locus for several vascular diseases, including FMD and coronary artery disease, with the putative causal noncoding variant at the rs9349379 locus acting as a potential enhancer for the endothelin-1 (EDN1) gene.. This study sought to test the association between the rs9349379 genotype and SCAD.. Results from case control studies from France, United Kingdom, United States, and Australia were analyzed to test the association with SCAD risk, including age at first event, pregnancy-associated SCAD (P-SCAD), and recurrent SCAD.. The previously reported risk allele for FMD (rs9349379-A) was associated with a higher risk of SCAD in all studies. In a meta-analysis of 1,055 SCAD patients and 7,190 controls, the odds ratio (OR) was 1.67 (95% confidence interval [CI]: 1.50 to 1.86) per copy of rs9349379-A. In a subset of 491 SCAD patients, the OR estimate was found to be higher for the association with SCAD in patients without FMD (OR: 1.89; 95% CI: 1.53 to 2.33) than in SCAD cases with FMD (OR: 1.60; 95% CI: 1.28 to 1.99). There was no effect of genotype on age at first event, P-SCAD, or recurrence.. The first genetic risk factor for SCAD was identified in the largest study conducted to date for this condition. This genetic link may contribute to the clinical overlap between SCAD and FMD.

Topics: Adult; Aged; Australia; Case-Control Studies; Coronary Vessel Anomalies; Endothelin-1; Female; Fibromuscular Dysplasia; France; Genetic Loci; Humans; Male; Microfilament Proteins; Middle Aged; Prevalence; United Kingdom; United States; Vascular Diseases

Myocardial bridging (MB) is associated with clinical and metabolic evidence of ischaemia. In the present study, we aimed to evaluate the extent of atherosclerosis and endothelial dysfunction in patients with MB. The study population consisted of 15 patients with MB [9 women (60%), aged 56 +/- 9 years] and 14 control subjects [8 women (57%), aged 54 +/- 10 years]. All patients underwent coronary angiography. The femoral artery and coronary sinus endothelin-1 (ET-1) and nitric oxide (NOx) plasma levels were measured before and after right atrial pacing in all subjects. Also, intravascular ultrasonography was performed in 13 patients with MB. With right atrial pacing, coronary sinus ET-1 levels increased significantly in patients with MB compared with baseline levels (5.77 +/- 6.76 versus 11.32 +/- 9.40 pg/ml, p < 0.05). The coronary sinus ET-1 levels remained unchanged in controls with pacing (3.99 +/- 4.00 versus 4.19 +/- 7.15 pg/ml, p > 0.05). There was no significant difference between the two groups according to the increase in NOx levels with atrial pacing. Ten (77%) of the 13 patients had plaque formation in the segments proximal to the bridge with an area stenosis of 37 +/- 21% (12% to 75%). In patients with MB, post-pacing levels of coronary sinus ET-1 correlated significantly with the cross-sectional area of the plaque (r = 0.65, p = 0,04). Increased ET-1 levels and the pathological data of intravascular ultrasonography may be associated with endothelial dysfunction and atherosclerosis development in patients with MB. The presence of atherosclerosis in the proximal segments to the bridge may contribute to the myocardial ischaemia detected in these patients.

Topics: Case-Control Studies; Coronary Vessel Anomalies; Endothelin-1; Female; Heart-Assist Devices; Humans; Male; Middle Aged; Myocardial Ischemia; Nitric Oxide; Ultrasonography

The relationship between alterations in the immunohistochemical expression of three vasoactive agents [endothelial nitric oxide synthase (eNOS), endothelin-1 (ET-1), and angiotensin-converting enzyme (ACE)] and the occurrence human atherosclerosis was investigated in relation to the myocardial bridge (MB) of the left anterior descending coronary artery (LAD), an anatomical site that experiences increased shear stress. Five millimetre cross-sections of LADs with MB from 22 autopsied cases were taken from the left coronary ostium to the cardiac apex and were immunohistochemically stained with antibodies against eNOS, ET-1, and ACE. The extent of atherosclerosis in each section was calculated using the atherosclerosis ratio (intimal cross-sectional area/medial cross-sectional area) determined by histomorphometry. The results were analysed according to their anatomical location relative to the MB, either proximal, beneath, or distal. The extent of atherosclerosis was significantly lower beneath the MB, compared with proximal and distal segments. The expression of eNOS, ET-1, and ACE was also significantly lower beneath the MB. The expression of these agents correlated significantly with the extent of atherosclerosis. Because nitric oxide, after its production by eNOS, is believed to be degraded by superoxide radicals, the effect of eNOS expression on atherosclerosis remains controversial. However, the present findings clearly indicate that the expression of ET-1 and ACE is directly related to the development of human coronary atherosclerosis in vivo through shear stress.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Agents; Coronary Artery Disease; Coronary Vessel Anomalies; Endothelin-1; Female; Humans; Immunoenzyme Techniques; Male; Middle Aged; Nitric Oxide Synthase; Peptidyl-Dipeptidase A; Stress, Mechanical