17 results on '"Danser AHJ"'
Search Results
2. Pharmacogenetics of ACE inhibition in stable coronary artery disease: steps towards tailored drug therapy.
- Author
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Brugts JJ, Danser AHJ, de Maat MPM, den Uil CA, Boersma E, Ferrari R, and Simoons ML
- Published
- 2008
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3. Newly developed renin and prorenin assays and the clinical evaluation of renin inhibitors.
- Author
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Schalekamp MAD, Derkx FHM, Deinum J, and Danser AHJ
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- 2008
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4. Different contributions of the angiotensin-converting enzyme C-domain and N-domain in subjects with the angiotensin-converting enzyme II and DD genotype.
- Author
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van Esch JHM, van Gool JMG, de Bruin RJA, Payne JR, Montgomery HE, Hectors M, Deinum J, Dive V, and Danser AHJ
- Published
- 2008
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5. Angiotensin II type 2 receptor-mediated vasodilation in human coronary microarteries.
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Batenburg WW, Garrelds IM, Bernasconi CC, Juillerat-Jeanneret L, van Kats JP, Saxena PR, Danser AHJ, Batenburg, Wendy W, Garrelds, Ingrid M, Bernasconi, Catherine Chapuis, Juillerat-Jeanneret, Lucienne, van Kats, Jorge P, Saxena, Pramod R, and Danser, A H Jan
- Published
- 2004
6. Blood pressure-independent effects of Rho-kinase inhibitors in the kidney?
- Author
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Danser AHJ and Jan Danser, A H
- Published
- 2004
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7. Targeting Angiotensinogen With N -Acetylgalactosamine-Conjugated Small Interfering RNA to Reduce Blood Pressure.
- Author
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Ye D, Cruz-López EO, Tu HC, Zlatev I, and Danser AHJ
- Subjects
- Humans, Acetylgalactosamine, Angiotensin II Type 1 Receptor Blockers pharmacology, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Blood Pressure, Renin metabolism, Renin-Angiotensin System physiology, RNA, Small Interfering pharmacology, Angiotensinogen genetics, Angiotensinogen metabolism, Hypertension therapy, Hypertension drug therapy
- Abstract
Blood pressure management involves antihypertensive therapies blocking the renin-angiotensin system (RAS). Yet, it might be inadequate due to poor patient adherence or the so-called RAS escape phenomenon, elicited by the compensatory renin elevation upon RAS blockade. Recently, evidence points toward targeting hepatic AGT (angiotensinogen) as a novel approach to block the RAS pathway that could circumvent the RAS escape phenomenon. Removing AGT, from which all angiotensins originate, should prevent further angiotensin generation, even when renin rises. Furthermore, by making use of a trivalent N -acetylgalactosamine ligand-conjugated small interfering RNA that specifically targets the degradation of hepatocyte-produced mRNAs in a highly potent and specific manner, it may be possible in the future to manage hypertension with therapy that is administered 1 to 2× per year, thereby supporting medication adherence. This review summarizes all current findings on AGT small interfering RNA in preclinical models, making a comparison versus classical RAS blockade with either ACE (angiotensin-converting enzyme) inhibitors or AT1 (angiotensin II type 1) receptor antagonists and AGT suppression with antisense oligonucleotides. It ends with discussing the first-in-human study with AGT small interfering RNA., Competing Interests: Disclosures E.O. Cruz-López was supported by the Mexican National Council of Science and Technology (grant No. 739513). I. Zlatev and H.-C. Tu are employees and stockholders of Alnylam Pharmaceuticals. A.H.J. Danser received a grant from Alnylam Pharmaceuticals, which has partially supported the work described in this review. The other author reports no conflicts.
- Published
- 2023
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8. Perivascular Adipose Tissue in Vascular Function: Does Locally Synthesized Angiotensinogen Play a Role?
- Author
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Cruz-López EO, Uijl E, and Danser AHJ
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- Adipose Tissue physiopathology, Blood Vessels physiopathology, Cardiovascular Diseases metabolism, Cardiovascular Diseases physiopathology, Humans, Signal Transduction, Adipose Tissue metabolism, Angiotensinogen metabolism, Blood Vessels metabolism, Renin-Angiotensin System, Vasoconstriction, Vasodilation
- Abstract
Abstract: In recent years, perivascular adipose tissue (PVAT) research has gained special attention in an effort to understand its involvement in vascular function. PVAT is recognized as an important endocrine organ that secretes procontractile and anticontractile factors, including components of the renin-angiotensin-aldosterone system, particularly angiotensinogen (AGT). This review critically addresses the occurrence of AGT in PVAT, its release into the blood stream, and its contribution to the generation and effects of angiotensins (notably angiotensin-(1-7) and angiotensin II) in the vascular wall. It describes that the introduction of transgenic animals, expressing AGT at 0, 1, or more specific location(s), combined with the careful measurement of angiotensins, has revealed that the assumption that PVAT independently generates angiotensins from locally synthesized AGT is incorrect. Indeed, selective deletion of AGT from adipocytes did not lower circulating AGT, neither under a control diet nor under a high-fat diet, and only liver-specific AGT deletion resulted in the disappearance of AGT from blood plasma and adipose tissue. An entirely novel scenario therefore develops, supporting local angiotensin generation in PVAT that depends on the uptake of both AGT and renin from blood, in addition to the possibility that circulating angiotensins exert vascular effects. The review ends with a summary of where we stand now and recommendations for future research., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2021
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9. Renal Angiotensinogen Is Predominantly Liver Derived in Nonhuman Primates.
- Author
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Kukida M, Cai L, Ye D, Sawada H, Katsumata Y, Franklin MK, Hecker PI, Campbell KS, Danser AHJ, Mullick AE, Daugherty A, Temel RE, and Lu HS
- Subjects
- Angiotensin I metabolism, Animals, Female, Humans, Macaca fascicularis, Mice, Species Specificity, Angiotensinogen metabolism, Kidney metabolism, Liver metabolism, Renin-Angiotensin System
- Abstract
[Figure: see text].
- Published
- 2021
- Full Text
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10. Hypertension and Prohypertensive Antineoplastic Therapies in Cancer Patients.
- Author
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van Dorst DCH, Dobbin SJH, Neves KB, Herrmann J, Herrmann SM, Versmissen J, Mathijssen RHJ, Danser AHJ, and Lang NN
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- Agammaglobulinaemia Tyrosine Kinase antagonists & inhibitors, Cancer Survivors, Carcinoma, Renal Cell etiology, Cardiotoxicity etiology, Humans, Hypertension complications, Hypertension drug therapy, Kidney Neoplasms etiology, MTOR Inhibitors adverse effects, Neoplasms etiology, Platinum Compounds adverse effects, Poly(ADP-ribose) Polymerase Inhibitors adverse effects, Proteasome Inhibitors adverse effects, Proto-Oncogene Proteins B-raf antagonists & inhibitors, Proto-Oncogene Proteins c-ret antagonists & inhibitors, Risk Factors, Vascular Endothelial Growth Factor A antagonists & inhibitors, Antineoplastic Agents adverse effects, Hypertension chemically induced, Neoplasms drug therapy
- Abstract
The development of a wide range of novel antineoplastic therapies has improved the prognosis for patients with a wide range of malignancies, which has increased the number of cancer survivors substantially. Despite the oncological benefit, cancer survivors are exposed to short- and long-term adverse cardiovascular toxicities associated with anticancer therapies. Systemic hypertension, the most common comorbidity among cancer patients, is a major contributor to the increased risk for developing these adverse cardiovascular events. Cancer and hypertension have common risk factors, have overlapping pathophysiological mechanisms and hypertension may also be a risk factor for some tumor types. Many cancer therapies have prohypertensive effects. Although some of the mechanisms by which these antineoplastic agents lead to hypertension have been characterized, further preclinical and clinical studies are required to investigate the exact pathophysiology and the optimal management of hypertension associated with anticancer therapy. In this way, monitoring and management of hypertension before, during, and after cancer treatment can be improved to minimize cardiovascular risks. This is vital to optimize cardiovascular health in patients with cancer and survivors, and to ensure that advances in terms of cancer survivorship do not come at the expense of increased cardiovascular toxicities.
- Published
- 2021
- Full Text
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11. Sex Differences in Response to Triptans: A Systematic Review and Meta-analysis.
- Author
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van Casteren DS, Kurth T, Danser AHJ, Terwindt GM, and MaassenVanDenBrink A
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- Female, Humans, Male, Observational Studies as Topic methods, Randomized Controlled Trials as Topic methods, Recurrence, Treatment Outcome, Tryptamines adverse effects, Migraine Disorders diagnosis, Migraine Disorders drug therapy, Sex Characteristics, Tryptamines therapeutic use
- Abstract
Objective: To examine the effect of sex on clinical response to triptans in migraine and to determine whether these differences are related to pharmacokinetics of triptans in men and women, we performed a systematic review and meta-analysis., Methods: We searched clinical trials distinguishing clinical response to or pharmacokinetic parameters of triptans between sexes in PubMed, MEDLINE, Cochrane Library, Embase, and Web of Science up to Dec 12, 2019. Analysis was based on data extracted from published reports. Male-to-female pooled risk ratios (RR) were calculated for clinical outcomes and pooled ratio of means (RoM) for pharmacokinetic outcomes using random-effects models., Results: Of 1,188 publications on clinical trials with triptans, 244 were identified with sex-related search terms. Only 19 publications presented sex-specific results, comprising n = 2,280 men and n = 13,899 women. No sex differences were revealed for 2-hour headache and pain-free responses, but men had a lower risk for headache recurrence (male-to-female RR 0.64, 95% confidence interval [CI]: 0.55-0.76, Q = 0.81) and adverse events (RR 0.82, 95% CI: 0.72-0.93, Q = 4.93). Men had lower drug exposure with lower area under the curve (RoM 0.69, 95% CI: 0.60-0.81, Q = 18.06) and peak drug concentration (RoM 0.72, 95% CI: 0.64-0.82, Q = 8.24) than women., Conclusions: Remarkably few publications about sex differences in triptan response are available. The limited number of eligible studies show sex differences in adverse event frequency, which may be partly because of drug exposure differences. This higher drug exposure in women is not reflected in different response rates. Despite higher exposure, women have higher headache recurrence rates possibly because of longer attack duration related to sex hormonal changes., (© 2020 American Academy of Neurology.)
- Published
- 2021
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12. Lasmiditan inhibits calcitonin gene-related peptide release in the rodent trigeminovascular system.
- Author
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Labastida-Ramírez A, Rubio-Beltrán E, Haanes KA, Chan KY, Garrelds IM, Johnson KW, Danser AHJ, Villalón CM, and MaassenVanDenBrink A
- Subjects
- Animals, Benzamides, Calcitonin, Male, Mice, Mice, Inbred C57BL, Piperidines, Pyridines, Rats, Rats, Sprague-Dawley, Serotonin Receptor Agonists, Calcitonin Gene-Related Peptide
- Abstract
Migraine headache pathophysiology involves trigeminovascular system activation, calcitonin gene-related peptide (CGRP) release, and dysfunctional nociceptive transmission. Triptans are 5-HT1B/1D/(1F) receptor agonists that prejunctionally inhibit trigeminal CGRP release, but their vasoconstrictor properties limit their use in migraine patients with cardiovascular disease. By contrast, lasmiditan is a novel antimigraine and selective 5-HT1F receptor agonist devoid of vasoconstrictor properties. On this basis, this study has investigated the modulation of trigeminal CGRP release by lasmiditan. For this purpose, we have comparatively analysed the inhibition of several components of the trigeminovascular system induced by lasmiditan and sumatriptan through: ex vivo KCl-induced CGRP release from isolated dura mater, trigeminal ganglion, and trigeminal nucleus caudalis of mice; and in vivo dural vasodilation in the rat closed-cranial window model induced by endogenous (electrical stimulation and capsaicin) and exogenous CGRP. The ex vivo release of CGRP was similarly inhibited by sumatriptan and lasmiditan in all trigeminovascular system components. In vivo, intravenous (i.v.) lasmiditan or higher doses of sumatriptan significantly attenuated the vasodilatory responses to endogenous CGRP release, but not exogenous CGRP effects. These data suggest that lasmiditan prejunctionally inhibits CGRP release in peripheral and central trigeminal nerve terminals. Because lasmiditan is a lipophilic drug that crosses the blood-brain barrier, additional central sites of action remain to be determined.
- Published
- 2020
- Full Text
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13. Targeting angiotensinogen with RNA-based therapeutics.
- Author
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Ren L, Colafella KMM, Bovée DM, Uijl E, and Danser AHJ
- Subjects
- Angiotensinogen genetics, Animals, Humans, Oligonucleotides, Antisense therapeutic use, RNA, Small Interfering therapeutic use, Renin-Angiotensin System drug effects, Angiotensinogen antagonists & inhibitors, Hypertension drug therapy
- Abstract
Purpose of Review: To summarize all available data on targeting angiotensinogen with RNA-based therapeutics as a new tool to combat cardiovascular diseases., Recent Findings: Liver-targeted, stable antisense oligonucleotides and small interfering RNA targeting angiotensinogen are now available, and may allow treatment with at most a few injections per year, thereby improving adherence. Promising results have been obtained in hypertensive animal models, as well as in rodent models of atherosclerosis, polycystic kidney disease and pulmonary fibrosis. The next step will be to evaluate the optimal degree of suppression, synergy with existing renin-angiotensin-aldosterone system blockers, and to determine harmful effects of suppressing angiotensinogen in the context of common comorbidities, such as heart failure and chronic kidney disease., Summary: Targeting angiotensinogen with RNA-based therapeutics is a promising new tool to treat hypertension and diseases beyond. Their long-lasting effects are particularly exciting, and if translated to a clinical application of at most a few administrations per year, may help to eliminate nonadherence.
- Published
- 2020
- Full Text
- View/download PDF
14. Tribute to Paul M. Vanhoutte, MD, PhD (1940-2019).
- Author
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Boulanger CM, Baretella O, Blaise G, Bond RA, Cai Y, Chan CKY, Chataigneau T, Chen MJ, Chen H, Cheng Y, Clement DL, Cohen RA, Collis M, Danser AHJ, de Mey J, Detremmerie CMS, Duprez D, Feletou M, Flavahan N, Gao Y, Guo Y, Hoeffner U, Houston DS, Huang IB, Huang Y, Iliano S, Junquero D, Katusic ZS, Komori K, Lee MYK, Leung SWS, Li Z, Liang SC, Liu JTC, Luscher TF, Michel F, Miller VM, Mombouli JV, Morrison K, Muldoon SM, O'Rourke S, Perrault L, Quignard JF, Rusch NJ, Sanchez-Ferrer CF, Schini-Kerth V, Shen K, Shi Y, Song E, Sun KWY, Taddei S, Tang EHC, Tuncer M, van den Ende R, Vedernikov Y, Verbeuren TJ, Webb C, Weigert A, Wong KHK, Xu C, Yang K, Ying F, Zellers T, Zhao Y, Zou Q, and Shimokawa H
- Published
- 2019
- Full Text
- View/download PDF
15. Angiotensinogen and Megalin Interactions Contribute to Atherosclerosis-Brief Report.
- Author
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Ye F, Wang Y, Wu C, Howatt DA, Wu CH, Balakrishnan A, Mullick AE, Graham MJ, Danser AHJ, Wang J, Daugherty A, and Lu HS
- Subjects
- Angiotensin II biosynthesis, Animals, Female, Hypercholesterolemia complications, Low Density Lipoprotein Receptor-Related Protein-2 antagonists & inhibitors, Male, Mice, Mice, Inbred C57BL, Oligonucleotides, Antisense pharmacology, Renin-Angiotensin System physiology, Angiotensinogen physiology, Atherosclerosis etiology, Low Density Lipoprotein Receptor-Related Protein-2 physiology
- Abstract
Objective- AGT (Angiotensinogen) is the unique precursor of the renin-angiotensin system that is sequentially cleaved by renin and ACE (angiotensin-converting enzyme) to produce Ang II (angiotensin II). In this study, we determined how these renin-angiotensin components interact with megalin in kidney to promote atherosclerosis. Approach and Results- AGT, renin, ACE, and megalin were present in the renal proximal convoluted tubules of wild-type mice. Hepatocyte-specific AGT deficiency abolished AGT protein accumulation in proximal tubules and diminished Ang II concentrations in kidney, while renin was increased. Megalin was most abundant in kidney and exclusively present on the apical side of proximal tubules. Inhibition of megalin by antisense oligonucleotides (ASOs) led to ablation of AGT and renin proteins in proximal tubules, while leading to striking increases of urine AGT and renin concentrations, and 70% reduction of renal Ang II concentrations. However, plasma Ang II concentrations were unaffected. To determine whether AGT and megalin interaction contributes to atherosclerosis, we used both male and female low-density lipoprotein receptor
-/- mice fed a saturated fat-enriched diet and administered vehicles (PBS or control ASO) or megalin ASO. Inhibition of megalin did not affect plasma cholesterol concentrations, but profoundly reduced atherosclerotic lesion size in both male and female mice. Conclusions- These results reveal a regulatory role of megalin in the intrarenal renin-angiotensin homeostasis and atherogenesis, positing renal Ang II to be an important contributor to atherosclerosis that is mediated through AGT and megalin interactions.- Published
- 2019
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16. (Pro)renin Receptor Inhibition Reprograms Hepatic Lipid Metabolism and Protects Mice From Diet-Induced Obesity and Hepatosteatosis.
- Author
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Ren L, Sun Y, Lu H, Ye D, Han L, Wang N, Daugherty A, Li F, Wang M, Su F, Tao W, Sun J, Zelcer N, Mullick AE, Danser AHJ, Jiang Y, He Y, Ruan X, and Lu X
- Subjects
- Acetyl-CoA Carboxylase metabolism, Adaptor Proteins, Vesicular Transport metabolism, Animals, Cells, Cultured, Diet, High-Fat adverse effects, Fatty Liver etiology, Gene Silencing, Hep G2 Cells, Humans, Male, Mice, Mice, Inbred C57BL, Obesity etiology, Pyruvate Dehydrogenase Complex metabolism, Receptors, Cell Surface genetics, Prorenin Receptor, Fatty Liver metabolism, Hepatocytes metabolism, Lipid Metabolism, Obesity metabolism, Receptors, Cell Surface metabolism
- Abstract
Rationale: An elevated level of plasma LDL (low-density lipoprotein) is an established risk factor for cardiovascular disease. Recently, we reported that the (pro)renin receptor ([P]RR) regulates LDL metabolism in vitro via the LDLR (LDL receptor) and SORT1 (sortilin-1), independently of the renin-angiotensin system., Objectives: To investigate the physiological role of (P)RR in lipid metabolism in vivo., Methods and Results: We used N-acetylgalactosamine modified antisense oligonucleotides to specifically inhibit hepatic (P)RR expression in C57BL/6 mice and studied the consequences this has on lipid metabolism. In line with our earlier report, hepatic (P)RR silencing increased plasma LDL-C (LDL cholesterol). Unexpectedly, this also resulted in markedly reduced plasma triglycerides in a SORT1-independent manner in C57BL/6 mice fed a normal- or high-fat diet. In LDLR-deficient mice, hepatic (P)RR inhibition reduced both plasma cholesterol and triglycerides, in a diet-independent manner. Mechanistically, we found that (P)RR inhibition decreased protein abundance of ACC (acetyl-CoA carboxylase) and PDH (pyruvate dehydrogenase). This alteration reprograms hepatic metabolism, leading to reduced lipid synthesis and increased fatty acid oxidation. As a result, hepatic (P)RR inhibition attenuated diet-induced obesity and hepatosteatosis., Conclusions: Collectively, our study suggests that (P)RR plays a key role in energy homeostasis and regulation of plasma lipids by integrating hepatic glucose and lipid metabolism., (© 2018 American Heart Association, Inc.)
- Published
- 2018
- Full Text
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17. Calcitonin Gene-Related Peptide Receptor Agonism: A Double-Edged Sword?
- Author
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Danser AHJ and MaassenVanDenBrink A
- Subjects
- Cardiomegaly, Heart Failure, Humans, Hypertension, Calcitonin Gene-Related Peptide, Receptors, Calcitonin Gene-Related Peptide
- Published
- 2017
- Full Text
- View/download PDF
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