Hypertension and congenital aortic valve malformations are frequent causes of ascending aortic aneurysms. The molecular mechanisms of aneurysm formation under these circumstances are not well understood. Reference genes for gene activity studies in aortic tissue that are not influenced by aortic valve morphology and its hemodynamic consequences, aortic dilatation, hypertension, or antihypertensive medication are not available so far. This study determines genes in ascending aortic tissue that are independent of these parameters. Tissue specimens from dilated and undilated ascending aortas were obtained from 60 patients (age ≤70 years) with different morphologies of the aortic valve (tricuspid undilated n = 24, dilated n = 11; bicuspid undilated n = 6, dilated n = 15; unicuspid dilated n = 4). Of the studied individuals, 36 had hypertension, and 31 received ACE inhibitors or AT1 receptor antagonists. The specimens were obtained intraoperatively from the wall of the ascending aorta. We analyzed the expression levels of 32 candidate reference genes by quantitative RT-PCR (RT-qPCR). Differential expression levels were assessed by parametric statistics. The expression analysis of these 32 genes by RT-qPCR showed that EIF2B1, ELF1, and PPIA remained constant in their expression levels in the different specimen groups, thus being insensitive to aortic valve morphology, aortic dilatation, hypertension, and medication with ACE inhibitors or AT1 receptor antagonists. Unlike many other commonly used reference genes, the genes EIF2B1, ELF1, and PPIA are neither confounded by aortic comorbidities nor by antihypertensive medication and therefore are most suitable for gene expression analysis of ascending aortic tissue.

Although RA rings of patients with a long duration of diabetes have decreased maximum contraction forces, their relative vasoconstriction after norepinephrine, endothelium-dependent relaxation and smooth muscle relaxation was similar to non-diabetic patients. We thus conclude that the RA is an adequate arterial conduit in the patient with diabetes mellitus.

Background Bicuspid aortic valves (BAVs) predispose to ascending aortic aneurysm. Turbulent blood flow and genetic factors have been proposed as underlying mechanisms. Endothelial nitric oxide synthase (eNOS) has been implicated in BAV aortopathy, and its expression is regulated by wall shear stress. We hypothesized that if turbulent flow induces aneurysm formation in patients with a BAV, regional differences in eNOS expression would be observed in BAVs. Methods and Results Ascending aortic specimens were harvested intraoperatively from 48 patients with tricuspid aortic valve (19 dilated, 29 nondilated) and 38 with BAV (28 dilated, 10 nondilated) undergoing cardiac surgery. eNOS mRNA and protein concentration were analyzed at the convex and concave aortic wall. In nondilated aortas, eNOS mRNA and protein concentration were decreased in BAV compared with tricuspid aortic valve (all P <0.05). eNOS expression was increased in association with dilation in BAV aortas ( P =0.03), but not in tricuspid aortic valve aortas ( P =0.63). There were no regional differences in eNOS mRNA or protein concentration in BAV aortas (all P >0.05). However, eNOS expression was increased at the concave wall (versus convexity) in tricuspid aortic valve dilated aortas (all P <0.05). Conclusions Dysregulated eNOS occurs independent of dilation in BAV aortas, suggesting a potential role for aberrantly regulated eNOS expression in the development of BAV‐associated aneurysms. The absence of regional variations of eNOS expression suggests that eNOS dysregulation in BAV aortas is the result of underlying genetic factors associated with BAV disease, rather than changes stimulated by hemodynamic alterations. These findings provide insight into the underlying mechanisms of aortic dilation in patients with a BAV.

Background/Aim: Upper gastrointestinal bleeding (UGIB) is one of the most frequent gastrointestinal complications after cardiac surgery with cardiopulmonary bypass (CPB). Endothelin expression and microcirculatory dysfunction have been shown to be involved in UGIB. The aim of this study was to analyze the effect of vasopressin during CPB on the gastric mucosal microcirculation and the involvement of the endothelin system. Methods: Eighteen pigs were randomized into three groups (n = 6 each): group I = sham, group II = CPB (1-hour CPB) and group III = CPB + vasopressin (1-hour CPB and vasopressin administration during CPB to maintain baseline arterial pressure). All animals were observed for a further 90 min after termination of CPB. Systemic hemodynamics as well as blood flow and oxygen saturation of the gastric mucosa were measured continuously. At the end of the experiment, the gastric mucosal expressions of endothelin-1 (ET-1) and its receptor subtypes A (ET_A) and B (ET_B) were determined by polymerase chain reaction. Gastric mucosal injury, apoptotic cell death and leukocytic infiltration were determined by histology and immunohistochemical analyses of cleaved caspase-3 and myeloperoxidase. Results: CPB decreased gastric microvascular perfusion, which was associated with an increased expression of ET-1 and ET_A. Vasopressin aggravated the CPB-associated malperfusion, whereas it completely abrogated the upregulation of ET-1 and ET_A. Interestingly, vasopressin did not induce gastric mucosal morphologic injury, leukocytic infiltration or apoptotic cell death. Conclusion: Vasopressin aggravates CPB-associated microvascular malperfusion of the gastric mucosa but does not induce gastric mucosal injury.