@article{LuHasanZengetal.2017,
  author    = {Lu, Yong-Ping and Hasan, Ahmed A. and Zeng, Shufei and Hocher, Berthold},
  title     = {Plasma ET-1 concentrations are elevated in pregnant women with hypertension - meta-analysis of clinical studies},
  series = {Kidney \& blood pressure research : official organ of the Gesellschaft f{\"u}r Nephrologie ; official organ of the Deutsche Liga zur Bek{\"a}mpfung des Hohen Blutdruckes e.V., Deutsche Hypertonie-Gesellschaft},
  volume    = {42},
  journal   = {Kidney \& blood pressure research : official organ of the Gesellschaft f{\"u}r Nephrologie ; official organ of the Deutsche Liga zur Bek{\"a}mpfung des Hohen Blutdruckes e.V., Deutsche Hypertonie-Gesellschaft},
  number    = {4},
  publisher = {Karger},
  address   = {Basel},
  issn      = {1420-4096},
  doi       = {10.1159/000482004},
  pages     = {654 -- 663},
  year      = {2017},
  abstract  = {Background/Aims: The ET system might be involved in the pathogenesis of hypertensive disorders during pregnancy. The objective is to analyse the impact of ET-1 in hypertensive pregnant women by a strict meta-analysis of published human clinical studies. Methods: Based on the principle of Cochrane systematic reviews, Cohort studies in PubMed (Medline), Google Scholar and China Biological Medicine Database (CBM-disc) designed to identify the role of endothelin-1 (ET-1) in the pathophysiology of gestational hypertension and preeclampsia were screened. Review Manager Version 5.0 (Rev-Man 5.0) was applied for statistical analysis. Mean difference and 95\% confidence interval (CI) were shown in inverse variance (IV) fixed-effects model or IV random-effects model. Results: Sixteen published cohort studies including 1739 hypertensive cases and 409 controls were used in the meta-analysis. ET-1 plasma concentrations were higher in hypertensive pregnant women as compared to the controls (mean difference between groups: 19.02 [15.60～22.44], P < 0.00001,). These finding were driven by severity of hypertension and/or degree of proteinuria. Conclusion: Plasma ET-1 concentrations are elevated in hypertensive disorders during human pregnancy. In particular women with preeclampsia (hypertensive pregnant women with proteinuria) have substantially elevated plasma ET-1 concentration as compared to pregnant women with normal blood pressure.},
  language  = {en}
}
@article{XuLuHasanetal.2017,
  author    = {Xu, Mei and Lu, Yong-Ping and Hasan, Ahmed A. and Hocher, Berthold},
  title     = {Plasma ET-1 concentrations are elevated in patients with hypertension meta-analysis of clinical studies},
  series = {Kidney \& blood pressure research : official organ of the Gesellschaft f{\"u}r Nephrologie ; official organ of the Deutsche Liga zur Bek{\"a}mpfung des Hohen Blutdruckes e.V., Deutsche Hypertonie-Gesellschaft},
  volume    = {42},
  journal   = {Kidney \& blood pressure research : official organ of the Gesellschaft f{\"u}r Nephrologie ; official organ of the Deutsche Liga zur Bek{\"a}mpfung des Hohen Blutdruckes e.V., Deutsche Hypertonie-Gesellschaft},
  number    = {2},
  publisher = {Karger},
  address   = {Basel},
  issn      = {1420-4096},
  doi       = {10.1159/000477572},
  pages     = {304 -- 313},
  year      = {2017},
  abstract  = {Background/Aims: A recent study revealed that global overexpression of ET-1 causes a slight reduction in systemic blood pressure. Moreover, heterozygous ET-1 knockout mice are hypertensive. The role of ET-1 in human hypertension was so far not addressed by a strict meta-analysis of published human clinical studies. Methods: We included studies published between January 1, 1990 and February 28, 2017. We included case control studies analyzing untreated essential hypertension or hypertensive patients where antihypertensive medication was discontinued for at least two weeks. Based on the principle of Cochrane systematic reviews, case control studies (CCSs) in PubMed (Medline) and Google Scholar designed to identify the role of endothelin-1 (ET-1) in the pathophysiological of hypertension were screened. Review Manager Version 5.0 (Rev-Man 5.0) was applied for statistical analysis. Mean difference and 95\% confidence interval (CI) were shown in inverse variance (IV) fixed-effects model or IV random-effects models. Results: Eleven studies fulfilling our in-and exclusion criteria were eligible for this meta-analysis. These studies included 450 hypertensive patients and 328 controls. Our meta-analysis revealed that ET-1 plasma concentrations were higher in hypertensive patients as compared to the control patients [mean difference between groups 1.57 pg/mL, 95\%Ci [0.47 similar to 2.68, P = 0.005]. These finding were driven by patients having systolic blood pressure higher than 160 mmHg and diastolic blood pressure higher than 100 mmHg. Conclusions: This meta-analysis showed that hypertensive patients do have elevated plasma ET-1 concentrations. This finding is driven by those patients with high systolic/diastolic blood pressure. Given that the ET-1 gene did not appear in any of the whole genome association studies searching for hypertension associated gene loci, it is very likely that the elevated plasma ET-1 concentrations in hypertensive patients are secondary to hypertension and may reflect endothelial cell damage.},
  language  = {en}
}
@article{LuReichetzederPrehnetal.2018,
  author    = {Lu, Yong-Ping and Reichetzeder, Christoph and Prehn, Cornelia and Yin, Liang-Hong and Yun, Chen and Zeng, Shufei and Chu, Chang and Adamski, Jerzy and Hocher, Berthold},
  title     = {Cord blood Lysophosphatidylcholine 16:1 is positively associated with birth weight},
  series = {Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology},
  volume    = {45},
  journal   = {Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology},
  number    = {2},
  publisher = {Karger},
  address   = {Basel},
  issn      = {1015-8987},
  doi       = {10.1159/000487118},
  pages     = {614 -- 624},
  year      = {2018},
  abstract  = {Background/Aims: Impaired birth outcomes, like low birth weight, have consistently been associated with increased disease susceptibility to hypertension in later life. Alterations in the maternal or fetal metabolism might impact on fetal growth and influence birth outcomes. Discerning associations between the maternal and fetal metabolome and surrogate parameters of fetal growth could give new insight into the complex relationship between intrauterine conditions, birth outcomes, and later life disease susceptibility. Methods: Using flow injection tandem mass spectrometry, targeted metabolomics was performed in serum samples obtained from 226 mother/child pairs at delivery. Associations between neonatal birth weight and concentrations of 163 maternal and fetal metabolites were analyzed. Results: After FDR adjustment using the Benjamini-Hochberg procedure lysophosphatidylcholines (LPC) 14:0, 16:1, and 18:1 were strongly positively correlated with birth weight. In a stepwise linear regression model corrected for established confounding factors of birth weight, LPC 16: 1 showed the strongest independent association with birth weight (CI: 93.63 - 168.94; P = 6.94x10(-11)). The association with birth weight was stronger than classical confounding factors such as offspring sex (CI: - 258.81- -61.32; P = 0.002) and maternal smoking during pregnancy (CI: -298.74 - -29.51; P = 0.017). Conclusions: After correction for multiple testing and adjustment for potential confounders, LPC 16:1 showed a very strong and independent association with birth weight. The underlying molecular mechanisms linking fetal LPCs with birth weight need to be addressed in future studies. (c) 2018 The Author(s) Published by S. Karger AG, Basel},
  language  = {en}
}
@article{WengenmayerKrikovMuelleretal.2011,
  author    = {Wengenmayer, Christina and Krikov, Maxim and Mueller, Susanne and Lucht, Kristin and Villringer, Arno and Hocher, Berthold and Unger, Thomas and Thoene-Reineke, Christa},
  title     = {Novel therapy approach in primary stroke prevention simultaneous inhibition of endothelin converting enzyme and neutral endopeptidase in spontaneously hypertensive, stroke-prone rats improves survival},
  series = {Neurological research : a journal of progress in neurosurgery and neurosciences},
  volume    = {33},
  journal   = {Neurological research : a journal of progress in neurosurgery and neurosciences},
  number    = {2},
  publisher = {Routledge, Taylor \& Francis Group},
  address   = {Leeds},
  issn      = {0161-6412},
  doi       = {10.1179/016164111X12881719352534},
  pages     = {201 -- 207},
  year      = {2011},
  abstract  = {Objectives: Stroke, frequently a consequence of hypertension, is one of the leading causes of death and neurological disabilities worldwide. In the ischemic brain, levels of endothelin-1, one of the most potent vasoconstrictors, are raised. Anti-inflammatory and neuroprotective effects of endothelin antagonists after stroke have been described in literature. Based on these findings, we investigated the protective effect of the endothelin converting enzyme/neutral endopeptidase blocker, SLV 338, in salt-loaded, stroke-prone, spontaneously hypertensive rats. Methods: Male, 8-week-old spontaneously hypertensive stroke-prone rats were put on a high salt diet and treated with either 30 mg/kg or 100 mg/kg SLV 338 or vehicle for 27 weeks. Blood pressure, neurological outcome, body weight, and mortality were investigated throughout treatment. In weeks 1 and 9, animals were housed in metabolic cages for collection of urinary and blood samples and assessment of salt water and food intake. In weeks 22 and 27, additional blood samples were taken. At the end of the study, all brains were analyzed using magnetic resonance imaging. Results: SLV 338 was well tolerated in all animals. Neurological outcome and infarct size were similar in all groups. Albuminuria was considerably delayed and the incidence of stroke significantly lowered in treated animals. In spontaneously hypertensive stroke-prone rats, treatment with SLV 338 significantly (P=0.01) improved survival in comparison to the vehicle treated group in a blood pressure-independent manner. Discussion: Our data in spontaneously hypertensive stroke-prone rats demonstrate that combined endothelin converting enzyme/neutral endopeptidase inhibition could offer a new therapeutic approach for primary stroke prevention and improvement of mortality. The mechanism seems to be blood pressure-independent.},
  language  = {en}
}
@article{HuberTreszlReibisetal.2013,
  author    = {Huber, Matthias and Treszl, Andras and Reibis, Rona Katharina and Teichmann, Christopher and Zergibel, Irina and Bolbrinker, Juliane and Scholze, Juergen and Wegscheider, Karl and V{\"o}ller, Heinz and Kreutz, Reinhold},
  title     = {Genetics of melatonin receptor type 2 is associated with left ventricular function in hypertensive patients treated according to guidelines},
  series = {European journal of internal medicine : official journal of the European Federation of Internal Medicine},
  volume    = {24},
  journal   = {European journal of internal medicine : official journal of the European Federation of Internal Medicine},
  number    = {7},
  publisher = {Elsevier},
  address   = {Amsterdam},
  issn      = {0953-6205},
  doi       = {10.1016/j.ejim.2013.03.015},
  pages     = {650 -- 655},
  year      = {2013},
  abstract  = {Background: Melatonin exerts multiple biological effects with potential impact on human diseases. This is underscored by genetic studies that demonstrated associations between melatonin receptor type 2 gene (MTNR1B) polymorphisms and characteristics of type 2 diabetes. We set out to test the hypothesis whether genetic variants at MTNR1B are also relevant for other disease phenotypes within the cardiovascular continuum. We thus investigated single nucleotide polymorphisms (SNPs) of MTNR1B in relation to blood pressure (BP) and cardiac parameters in hypertensive patients. Methods: Patients (n = 605, mean age 56.2 +/- 9.4 years, 82.3\% male) with arterial hypertension and cardiac ejection fraction (EF) >= 40\% were studied. Cardiac parameters were assessed by echocardiography. Results: The cohort comprised subjects with coronary heart disease (73.1\%) and myocardial infarction (48.1\%) with a mean EF of 63.7 +/- 8.9\%. Analysis of SNPs rs10830962, rs4753426, rs12804291, rs10830963, and rs3781638 revealed two haplotypes 1 and 2 with frequencies of 0.402 and 0.277, respectively. Carriers with haplotype 1 (CTCCC) showed compared to non-carriers a higher mean 24-hour systolic BP (difference BP: 2.4 mm Hg, 95\% confidence interval (CI): 0.3 to 4.5 mm Hg, p = 0.023). Haplotype 2 (GCCGA) was significantly related to EF with an absolute increase of 1.8\% (CI: 0.45 to 3.14\%) in carriers versus non-carriers (p = 0.009). Conclusion: Genetics of MTNR1B point to impact of the melatonin signalling pathway for BP and left ventricular function. This may support the importance of the melatonin system as a potential therapeutic target.},
  language  = {en}
}