Due to progressive abdominal-venous congestion severe tricuspid regurgitation (TR) is a common cause of cardiorenal and cardiohepatic syndrome. We initiated the TRICAVAL study to compare ...interventional valve implantation into the inferior vena cava (CAVI) versus optimal medical therapy (OMT) in severe TR. In the present subanalysis, we aimed to evaluate the effects of CAVI on clinical signs of congestion, renal and hepatic function. TRICAVAL was an investigator-initiated, randomized trial. Twenty-eight patients with severe TR were randomized to OMT or CAVI using an Edwards Sapien XT valve. Probands who completed the 3-month follow-up (CAVI n = 8, OMT n = 10) were evaluated by medical history, clinical examination, and laboratory testing at baseline, 3 and 12 months. After 3 months, the CAVI group exhibited a significant reduction of body weight (from 80.7 69.0-87.7 kg to 75.5 63.8-84.6 kg, p < 0.05) and abdominal circumference (from 101.5 ± 13.8 cm to 96.3 ± 15.4 cm, p ≤ 0.01) and a trend to lower doses of diuretics compared to OMT. Renal and hepatic function parameters did not change significantly. Within a short-term follow-up, CAVI led to an improvement of clinical signs of venous congestion and a non-significant reduction of diuretic doses compared to OMT.
Consumption of green or black tea has been inversely associated with the development and progression of cardiovascular diseases. In this review, the current knowledge about protective effects of tea ...and tea constituents, particularly flavonoids, on the cardiovascular system is summarized. Underlying mechanisms for the beneficial effects of tea include vasculoprotective, antioxidative, antithrombogenic, anti‐inflammatory, and lipid‐lowering properties of tea flavonoids. Although promising experimental data on beneficial effects of tea in various cardiovascular diseases are available, results of clinical studies in humans are not uniform. A number of factors are discussed which may contribute to inconsistent data in humans. Overall, tea represents a promising tool for the prevention and treatment of cardiovascular disorders.
Periods of low energy supply are challenging conditions for organisms and cells during fasting or famine. Although changes in nutrient levels in the blood are first sensed by endothelial cells, ...studies on their metabolic adaptations to diminished energy supply are lacking. We analyzed the dynamic metabolic activity of human umbilical vein endothelial cells (HUVECs) in basal conditions and after serum starvation. Metabolites of glycolysis, the tricarboxylic acid (TCA) cycle, and the glycerol pathway showed lower levels after serum starvation, whereas amino acids had increased levels. A metabolic flux analysis with
C-glucose or
C-glutamine labeling for different time points reached a plateau phase of incorporation after 30 h for
C-glucose and after 8 h for
C-glutamine under both experimental conditions. Notably, we observed a faster label incorporation for both
C-glucose and
C-glutamine after serum starvation. In the linear range of label incorporation after 3 h, we found a significantly faster incorporation of central carbon metabolites after serum starvation compared to the basal state. These findings may indicate that endothelial cells develop increased metabolic activity to cope with energy deficiency. Physiologically, it can be a prerequisite for endothelial cells to form new blood vessels under unfavorable conditions during the process of angiogenesis in vivo.
Transarterial aortic valve implantation (TAVI) is a promising method for the treatment of high-risk patients with aortic stenosis. Because gender differences are known in aortic stenosis, the aim of ...this study was to compare procedural and short-term outcomes, left ventricular remodeling, and inflammatory status after TAVI in men and women. One hundred consecutive patients (42 men, 58 women) who underwent transfemoral TAVI (CoreValve in 83%, SAPIEN in 17%) were prospectively analyzed. Aortic stenosis severity was higher in women (mean valve area 0.7 ± 0.3 vs 0.8 ± 0.2 cm2 ). Women had better ejection fractions, smaller end-diastolic and end-systolic diameters, and more concentric hypertrophy at baseline. There were no differences in device success rate (99%), 30-day total mortality (2.4% in men, 3.4% in women), stroke (2.4% in men, 1.7% in women), or pacemaker rate (26.2% in men, 15.5% in women). Periprocedural complications and 3-month outcome were not different between the genders. After TAVI, regression of hypertrophy occurred in men and women, but improvement of the ejection fraction was significant only in women. N-terminal pro–B-type natriuretic peptide decreased to similar levels in the 2 genders. C-reactive protein and interleukin-6, elevated at baseline more in men than in women, decreased after TAVI and normalized at 3 months only in women. In conclusion, women clinically benefit from TAVI to a degree similar to that of men. However, there are gender differences involving the recovery response of the left ventricle after TAVI.
Differences in pharmacokinetics, pharmacodynamics, and physiology contribute to the phenomenon that women and men frequently respond differently to cardiovascular drugs. Hormonal influences, in ...addition, can play an important role: for example, the menstrual cycle, menopause, and pregnancy—as a result of fluctuations in concentrations of sexual steroids, and of changes in total body water—can be associated with gender-specific differences in the plasma levels of cardiovascular drugs. Clinical relevance accordingly results, especially for substances with a narrow therapeutic margin. This review treats the most important pharmacodynamic gender-relevant differences in this context, and surveys available evidence on the benefits of therapy of chronic cardiovascular diseases in women. On the whole, the study situation for women is appreciably less favourable than for men: owing to the fact that women are under-represented in most studies, and that few gender-specific analyses have been conducted.
Aims Increased levels of reactive oxygen species cause oxidative stress and severely damage lipids, proteins, and DNA. We have previously shown that partial proteasome inhibition induces an ...antioxidative gene pattern in endothelial cells. Here, we elucidate the mechanisms of proteasome inhibitor-mediated upregulation of antioxidative enzymes and cytoprotection. Methods and results Non-toxic proteasome inhibition upregulated mRNA and protein expression of superoxide dismutase 1 (SOD1) and haem oxygenase 1 (HO1) in several human endothelial and vascular smooth muscle cell types. Transcriptional activation of these enzymes was shown by inhibition of RNA polymerase II and nuclear run-on assays. Transfection of endothelial cells with luciferase reporter constructs revealed that upregulation can be largely confined to an antioxidant response element (ARE), which proved to be sufficient for transcriptional activation of SOD1 and HO1. Co-transfection studies and bandshift analyses confirmed binding of the antioxidative transcription factor NF-E2-related factor 2 (Nrf2)—which was stabilized by proteasome inhibition as shown by immunoblots—to the ARE site of HO1. Experiments with aortic endothelial and smooth muscle cells from Nrf2 wild-type and knockout mice revealed an essential role of Nrf2: in wild-type cells, proteasome inhibitor-mediated induction of SOD1 and HO1 was accompanied by protection of vascular cells against oxidative stress as determined by lactate dehydrogenase release assays. In contrast, proteasome inhibitor-mediated induction of antioxidative enzymes and cytoprotection were completely lost in cells from Nrf2 knockout mice. Conclusion Nrf2-dependent transcriptional activation of antioxidative enzymes is crucial for proteasome inhibitor-mediated protection of vascular cells against oxidative stress.
Abstract Objective Significant sex differences exist in cardiovascular diseases. Although an impact of gonadal hormones is presumed, it is largely unknown whether sexually dimorphic gene expression ...also plays a role and whether cells themselves show intrinsic sex differences. Methods We performed whole genome expression analyses in human umbilical vein endothelial cells (HUVEC) from 20 male and 20 female donors and compared levels of gene transcription between the sexes. To further assess whether there is a sex-specific response to stress, we subjected male and female HUVEC to shear for 24 h and analysed changes in gene expression. Results Genes indicative for greater immune responsiveness were stronger expressed in female compared to male HUVEC. There was a significant enrichment of 77 immune-related genes in female HUVEC. These increased transcriptional levels in female cells were verified for 20 genes by real-time RT-PCR. 6.7% of all mRNAs were regulated by shear stress. Female HUVEC showed a more pronounced transcriptional response to shear than did their male counterparts. In addition to quantitative differences, a number of genes were regulated in the opposite direction between the two sexes by shear stress. Functionally, female HUVEC showed a higher cell viability after serum starvation and an increased tube formation capacity compared to male cells. Conclusion These findings underscore the importance for differentiation between male and female cells in cell culture experiments. This may apply not only to endothelial cells but might be generalized to other cell types as well. The observed sexual dimorphisms in gene expression in endothelial cells may contribute to sex differences between males and females in endothelial function.
Echocardiographic differentiation of cardiac amyloidosis (CA) and Fabry disease (FD) is often challenging using standard echocardiographic parameters. We retrospectively analyzed the diagnostic ...accuracy of right heart and left atrial strain parameters to discriminate CA from FD using receiver operating characteristic curve analyses and logistic regression models. A total of 47 FD and 88 CA patients with left ventricular wall thickening were analyzed. The comparison of both cardiomyopathies revealed significantly reduced global and free wall longitudinal right ventricular strain (RVS; global RVS: CA - 13 ± 4%, n = 67, vs. FD - 18 ± 4%, n = 39, p < 0.001) as well as right atrial strain (RAS; reservoir RAS: CA 12 ± 8%, n = 70, vs. FD 26 ± 9%, n = 40, p < 0.001) and left atrial strain (LAS) in CA patients. Individually, global RVS as well as phasic LAS and RAS showed the highest diagnostic accuracy to distinguish CA and FD. The best diagnostic accuracy was achieved by combining the age, basal RV diameter, global RVS, and reservoir and conduit RAS (area under the curve 0.96 95% CI 0.90-1.00). Differential echocardiographic diagnostic work-up of patients with suspected CA or FD can be improved by integrating structural and functional parameters of the right heart and the left atrium.Trial registration: DRKS00027403.
Consumption of tea is inversely associated with cardiovascular diseases. However, the active compound(s) responsible for the protective effects of tea are unknown. Although many favorable ...cardiovascular effects in vitro are mediated by epigallocatechin gallate (EGCG), its contribution to the beneficial effects of tea in vivo remains unresolved. In a randomised crossover study, a single dose of 200 mg EGCG was applied in three different formulas (as green tea beverage, green tea extract (GTE), and isolated EGCG) to 50 healthy men. Flow-mediated dilation (FMD) and endothelial-independent nitro-mediated dilation (NMD) was measured before and two hours after ingestion. Plasma levels of tea compounds were determined after each intervention and correlated with FMD. FMD significantly improved after consumption of green tea containing 200 mg EGCG (p < 0.01). However, GTE and EGCG had no significant effect on FMD. NMD did not significantly differ between interventions. EGCG plasma levels were highest after administration of EGCG and lowest after consumption of green tea. Plasma levels of caffeine increased after green tea consumption. The results show that EGCG is most likely not involved in improvement of flow-mediated dilation by green tea. Instead, other tea compounds, metabolites or combinations thereof may play a role.
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