Endothelin-1 overexpression restores diastolic function in eNOS knockout mice

Vignon-Zellweger, Nicolas; Relle, Katharina; Kienlen, Elodie; Alter, Markus; Seider, Patrick; Sharkovska, Juliya; Heiden, Susi; Kalk, Philipp; Schwab, Karima; Albrecht-Küpper, Barbara; Theuring, Franz; Stasch, Johannes-Peter; Hocher, Berthold

doi:10.1097/hjh.0b013e3283450770

Cited by 25 publications

(23 citation statements)

References 57 publications

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“…Heart catheter examination of these mice revealed no major differences between WT mice and ET-1+/+ mice with the exception of a significantly decreased time of left ventricular relaxation constant (tau) in ET-1+/+ mice. Myocyte size and cardiac collagen content were similar in WT and ET-1+/+ mice [17]. However, under conditions of a 10-fold increase of cardiomyocyte-derived ET-1 production, observed in a mouse model of cardiomyocyte-specific ET-1 overexpression, the cardiac phenotype was characterized by an increased expression of inflammatory cytokines and an inflammatory cardiomyopathy leading to heart failure and death [41].…”

Section: Kidney Weight and Protein Excretionmentioning

confidence: 94%

“…This is remarkable, since blood pressure is clearly lower in ET-1+/+ mice in this age group indicating that there are obviously ET-1 mediated bloodpressure independent mechanisms increasing the heart weight. Vignon-Zellweger et al [17] demonstrated a two-fold elevated cardiac ET-1 mRNA expression in ET-1+/+ mice compared to the WT counterparts. Brain natriuretic peptide concentrations were slightly but not significantly higher in ET-1+/+ mice.…”

Section: Kidney Weight and Protein Excretionmentioning

confidence: 98%

“…Four studies reported heart rate data [6,12,16,17] (table 1). The overall effect was neutral: no differences concerning heart rate between WT and ET-1+/+ mice were detectable (P = 0.76), with minimal heterogeneity (P = 0.80, I 2 = 0%).…”

Section: Heart Rate (Global Et-1 Overexpression)mentioning

confidence: 99%

“…Three articles described HW/BW ratios [4,11,17] (table 1). Overall, the HW/BW ratio showed no difference between ET-1+/+ and WT mice (P = 0.28), with distinguished heterogeneity (P < 0.0001, I 2 = 96%).…”

Section: Heart Weight/body Weight (Hw/bw) Ratio (Global Et-1 Overexprmentioning

confidence: 99%

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Global Overexpression of ET-1 Decreases Blood Pressure - A Systematic Review and Meta-Analysis of ET-1 Transgenic Mice

Tsuprykov

Vignon-Zellweger

et al. 2016

Kidney Blood Press Res

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Background/Aims: ET-1 has independent effects on blood pressure regulation in vivo, it is involved in tubular water and salt excretion, promotes constriction of smooth muscle cells, modulates sympathetic nerve activity, and activates the liberation of nitric oxide. To determine the net effect of these partially counteracting mechanisms on blood pressure, a systematic meta-analysis was performed. Methods: Based on the principles of Cochrane systematic reviews, we searched in major literature databases - MEDLINE (PubMed), Embase, Google Scholar, and the China Biological Medicine Database (CBM-disc) - for articles relevant to the topic of the blood pressure phenotype of endothelin-1 transgenic (ET-1+/+) mice from January 1, 1988 to March 31, 2016. Review Manager Version 5.0 (Rev-Man 5.0) software was applied for statistical analysis. In total thirteen studies reported blood pressure data. Results: The meta-analysis of blood pressure data showed that homozygous ET-1 transgenic mice (ET-1+/+ mice) had a significantly lower blood pressure as compared to WT mice (mean difference: -2.57 mmHg, 95% CI: -4.98∼ -0.16, P = 0.04), with minimal heterogeneity (P = 0.86). A subgroup analysis of mice older than 6 months revealed that the blood pressure difference between ET-1+/+ mice and WT mice was even more pronounced (mean difference: -6.19 mmHg, 95% CI: -10.76∼ -1.62, P = 0.008), with minimal heterogeneity (P = 0.91). Conclusion: This meta-analysis provides robust evidence that global ET-1 overexpression in mice lowers blood pressure in an age-dependent manner. Older ET-1+/+ mice have a somewhat more pronounced reduction of blood pressure.

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Section: Kidney Weight and Protein Excretionmentioning

confidence: 94%

Section: Kidney Weight and Protein Excretionmentioning

confidence: 98%

Section: Heart Rate (Global Et-1 Overexpression)mentioning

confidence: 99%

Section: Heart Weight/body Weight (Hw/bw) Ratio (Global Et-1 Overexprmentioning

confidence: 99%

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Global Overexpression of ET-1 Decreases Blood Pressure - A Systematic Review and Meta-Analysis of ET-1 Transgenic Mice

Tsuprykov

Vignon-Zellweger

et al. 2016

Kidney Blood Press Res

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“…Endothelin-1 (ET-1) has been shown to play a key role in the pathogenesis of cardiac and renal diseases [1][2][3][4][5]. It is elevated in patients with essential hypertension [6] and in particular pregnant women with pregnancy induced hypertension [7].…”

Section: Introductionmentioning

confidence: 99%

Lipopolysaccharides (LPS) Induced Angiogenesis During Chicken Embryogenesis is Abolished by Combined ETA/ETB Receptor Blockade

Wang

Zhang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Angiogenesis plays a key role during embryonic development. The vascular endothelin (ET) system is involved in the regulation of angiogenesis. Lipopolysaccharides (LPS) could induce angiogenesis. The effects of ET blockers on baseline and LPS-stimulated angiogenesis during embryonic development remain unknown so far. Methods: The blood vessel density (BVD) of chorioallantoic membranes (CAMs), which were treated with saline (control), LPS, and/or BQ123 and the ETB blocker BQ788, were quantified and analyzed using an IPP 6.0 image analysis program. Moreover, the expressions of ET-1, ET-2, ET3, ET receptor A (ETRA), ET receptor B (ETRB) and VEGFR2 mRNA during embryogenesis were analyzed by semi-quantitative RT-PCR. Results: All components of the ET system are detectable during chicken embryogenesis. LPS increased angiogenesis substantially. This process was completely blocked by the treatment of a combination of the ETA receptor blockers-BQ123 and the ETB receptor blocker BQ788. This effect was accompanied by a decrease in ETRA, ETRB, and VEGFR2 gene expression. However, the baseline angiogenesis was not affected by combined ETA/ETB receptor blockade. Conclusion: During chicken embryogenesis, the LPS-stimulated angiogenesis, but not baseline angiogenesis, is sensitive to combined ETA/ETB receptor blockade.

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