Objectives: As the endothelin system participates in the regulation of cardiovascular homeostasis, the aim of this study was to analyse the role of endothelin system polymorphisms in influencing tilt-induced vasovagal syncope.
Methods: We evaluated 107 otherwise healthy subjects with recurrent unexplained syncope who underwent a head-up tilt test. All subjects were genotyped for the 3A/4A polymorphism of the EDN1 gene and the H323H T/C polymorphism of the EDNRA gene.
Results: Fifty-eight patients (54%) fainted. In terms of the EDNRA polymorphism, eight subjects (8%) had the T/T genotype, 41 were heterozygous (38%) and 58 homozygous (54%) for the C allele. Sixty subjects (56%) carried homozygosis for the 3A allele of the EDN1 polymorphism and 47 were heterozygous (44%). The 4A allele was significantly more frequent in the patients who responded positively to the tilt test than in those who did not: the relative odds ratios and confidence intervals at univariate and multivariate analyses were respectively 2.37 (1.07-5.26) and 2.41 (1.05-5.49). Comparisons with a control group further supported these data. Among the tilt-positive patients, the carriers of the 4A allele were more likely to have a vasodepressive pattern than those who were homozygous for the 3A variant.
Interpretation: The 3A/4A polymorphism of the EDN1 gene affects susceptibility to syncope, and the 4A variant associated with increased endothelin-1 expression may promote vasodepressive hemodynamic responses during tilt testing.
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http://dx.doi.org/10.1007/s10286-009-0519-y | DOI Listing |
Front Pharmacol
January 2025
Department of Cardiovascular Center, First Affiliated Hospital of Huzhou University, Huzhou, China.
The emergence of targeted anti-tumor drugs has significantly prolonged the lifespan and improved the prognosis of cancer patients. Among these drugs, vascular endothelial growth factor (VEGF) inhibitors, particularly novel small molecule tyrosine kinase inhibitors (TKIs), are extensively employed as VEGF inhibitors; however, they are also associated with a higher incidence of complications, with hypertension being the most prevalent cardiovascular toxic side effect. Currently, it is widely accepted that TKIs-induced hypertension involves multiple mechanisms including dysregulation of the endothelin (ET) axis, reduced bioavailability of nitric oxide (NO), imbalance in NO-ROS equilibrium system, vascular rarefaction, and activation of epithelial sodium calcium channels; nevertheless, excessive activation of ET system appears to be predominantly responsible for this condition.
View Article and Find Full Text PDFHypertens Res
January 2025
The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, China.
Contemporary anticancer drugs are often accompanied by varying degrees of cardiovascular toxicity, with hypertension emerging as one of the most prevalent side effects, particularly linked to inhibitors of vascular endothelial growth factor receptor (VEGFR) and tyrosine kinase inhibitors (TKIs). Hypertension induced by cancer therapies contributes to increased cardiovascular mortality in cancer patients and survivors. Given the shared common risk factors and overlapping pathophysiological mechanisms, hypertension is also a prevalent comorbidity in this patient population.
View Article and Find Full Text PDFEndocr Metab Immune Disord Drug Targets
January 2025
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif, 24227, 20006, Saudi Arabia.
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Kidney Int Rep
January 2025
Department of Cardiovascular Sciences, University of Leicester, Leicester, Leicestershire, UK.
Introduction: Endothelin A (ETA) receptor activation is a driver of proteinuria, kidney inflammation, and fibrosis in IgA nephropathy (IgAN). Atrasentan, a selective ETA receptor antagonist, has potential to reduce proteinuria and preserve kidney function in IgAN. ALIGN (NCT04573478) is a phase 3, randomized, double-blind, placebo-controlled clinical trial of atrasentan in patients with IgAN at high risk of kidney function loss.
View Article and Find Full Text PDFJ Mol Cell Cardiol Plus
March 2024
Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.
Sacubitril/valsartan (Sac/Val) belongs to the group of angiotensin receptor-neprilysin inhibitors and has been used for the treatment of heart failure (HF) for several years. The mechanisms that mediate the beneficial effects of Sac/Val are not yet fully understood. In this study we investigated whether Sac/Val influences the two proteolytic systems, the ubiquitin-proteasome system (UPS) and the autophagy-lysosomal pathway (ALP), in a mouse model of pressure overload induced by transverse aortic constriction (TAC) and in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) treated with endothelin-1 (ET1) serving as a human cellular model of hypertrophy.
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