endothelin-1 and Fibromuscular-Dysplasia

Fibromuscular Dysplasia (FMD) is “an idiopathic, segmental, non-atherosclerotic and non-inflammatory disease of the musculature of arterial walls, leading to stenosis of small and medium-sized arteries” (Persu, et al; 2014). FMD can lead to hypertension, arterial dissections, subarachnoid haemorrhage, stroke or mesenteric ischemia. The pathophysiology of the disease remains elusive. While familial cases are rare (<5%) in contemporary FMD registries, there is evidence in favour of the existence of multiple genetic factors involved in this vascular disease. Recent collaborative efforts allowed the identification of a first genetic locus associated with FMD. This intronic variant located in the phosphatase and actin regulator 1 gene (

Topics: Animals; Endothelin-1; Fibromuscular Dysplasia; Genetic Loci; Genetic Predisposition to Disease; Genomics; Humans; Microfilament Proteins; Transcriptional Activation

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

Topics: Benzamides; Cell Division; Drug Therapy, Combination; Endothelin-1; Endothelium, Vascular; Fibromuscular Dysplasia; Humans; Hypertension, Pulmonary; Imatinib Mesylate; Muscle, Smooth, Vascular; Phosphodiesterase Inhibitors; Piperazines; Prostaglandins; Pulmonary Artery; Pulmonary Disease, Chronic Obstructive; Pulmonary Embolism; Pyrimidines; Vasodilator Agents