Article
Cell Biology
Cristina Ortiz, Sabine Klein, Winfried H. Reul, Fernando Magdaleno, Stefanie Groeschl, Peter Dietrich, Robert Schierwagen, Frank E. Uschner, Sandra Torres, Christoph Hieber, Caroline Meier, Nico Kraus, Olaf Tyc, Maximilian Brol, Stefan Zeuzem, Christoph Welsch, Marco Poglitsch, Claus Hellerbrand, Mercedes Alfonso-Prieto, Fabio Mira, Ulrich auf dem Keller, Anja Tetzner, Andrew Moore, Thomas Walther, Jonel Trebicka
Summary: The development of liver fibrosis is associated with the contraction of hepatic stellate cells (HSC), but the interaction between neprilysin (NEP) and its substrate neuropeptide Y (NPY) in liver fibrosis is not well understood.NEP is derived from HSCs while NPY mainly comes from the splanchnic region and is cleaved by NEP to terminate contraction. NEP deficiency leads to less fibrosis but portal hypertension in mice models of liver injury. Combining NEP inhibitor with angiotensin II type 1 receptor blocker (ARB) or ACE inhibitor provides incremental benefits for fibrosis and portal hypertension. Administration of Entresto, a combination of ARB and NEP inhibitor, reduces hepatic fibrosis and portal pressure in mice.
Review
Peripheral Vascular Disease
Zhen-Yu Zhang, Yu-Ling Yu, Kei Asayama, Tine W. Hansen, Gladys E. Maestre, Jan A. Staessen
Summary: Additional digital content is available in the text.
Article
Pharmacology & Pharmacy
Edwyn O. Cruz-Lopez, Liwei Ren, Estrellita Uijl, Marian C. Clahsen-van Groningen, Richard van Veghel, Ingrid M. Garrelds, Oliver Domenig, Marko Poglitsch, Ivan Zlatev, Timothy Rooney, Anne Kasper, Paul Nioi, Don Foster, A. H. Jan Danser
Summary: This study found that siRNA targeting liver angiotensinogen can lower blood pressure in hypertensive diabetes and provide renal protection. The results suggest that this method may also be applicable for the treatment of diabetic kidney disease in humans.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Environmental Sciences
Md Shiblur Rahaman, Nathan Mise, Akihiko Ikegami, Cai Zong, Gaku Ichihara, Sahoko Ichihara
Summary: It has been established that arsenic exposure leads to hypertension in humans, but the underlying molecular mechanisms are not fully understood. This study explored the potential mechanisms by investigating the renin-angiotensin system (RAS). The findings suggest that arsenic-induced hypertension is mediated by oxidative stress-mediated inhibition of ACE2 and suppression of the vasoprotective axes of RAS.
Article
Multidisciplinary Sciences
Lise Desquilles, Luis Cano, Gevorg Ghukasyan, Nicolas Mouchet, Clemence Landreau, Anne Corlu, Bruno Clement, Bruno Turlin, Romain Desert, Orlando Musso
Summary: The study analyzed the expression and localization of ACE2 and TMPRSS2 in human liver cancers and non-tumor livers. The results showed that ACE2 and TMPRSS2 were mainly located at the biliary pole of tumor hepatocytes in liver cancers. In normal liver samples, ACE2 was distributed in hepatocyte's bile canaliculi, biliary epithelium, sinusoidal, and capillary endothelial cells. Additionally, tumors carrying mutated beta-catenin showed upregulated ACE2 expression, consistent with the predicted response sites in the ACE2 promoter. These findings reveal a potential link between liver cancer, liver diseases, and SARS-CoV-2 infection.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Luis Felipe Rodrigues, Bruno Rocha Avila Pelozin, Natan Daniel da Silva Junior, Ursula Paula Reno Soci, Everton Crivoi do Carmo, Gloria de Fatima Alves da Mota, Victoria Cachofeiro, Vicente Lahera, Edilamar Menezes Oliveira, Tiago Fernandes
Summary: Aerobic exercise training promotes angiogenesis through the miRNA-27a/b-ACE1/Ang II/VEGF axis and improves the redox balance in skeletal muscles. The involvement of the renin-angiotensin system suggests its important role in exercise training-induced vascular growth. miRNAs and RAS components are promising potential targets to modulate angiogenesis for combating vascular diseases, as well as potential biomarkers to monitor training interventions and physical performance.
Article
Pharmacology & Pharmacy
Zuzana Huskova, Sona Kikerlova, Janusz Sadowski, Petra Alanova, Lenka Sedlakova, Frantisek Papousek, Jan Neckar
Summary: The study confirmed improved cardiac tolerance to ischemia/reperfusion injury in hypertensive cardiohypertrophied rats and found that locally produced ANG II in the heart, through activation of AT1 receptors, was not the mechanism underlying infarct size reduction.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Critical Care Medicine
Xinjun Mao, Katharina Krenn, Thomas Tripp, Verena Tretter, Roman Reindl-Schwaighofer, Felix Kraft, Bruno K. Podesser, Yi Zhu, Marko Poglitsch, Oliver Domenig, Dietmar Abraham, Roman Ullrich
Summary: Ventilator-induced lung injury (VILI) can cause significant damage to the lungs, and the activation of the renin-angiotensin system (RAS) can further worsen this damage. This study examined the activation profiles of the RAS in VILI patients and investigated the potential protective effects of angiotensin (Ang) 1-7 supplementation or angiotensin-converting enzyme (ACE) inhibition with captopril.
CRITICAL CARE MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Zainab Mastoor, Yolanda Diz-Chaves, Lucas C. Gonzalez-Matias, Federico Mallo
Summary: Impaired hepatic lipids and carbohydrates metabolism can lead to various metabolic disorders. The renin-angiotensin system plays an important role in this process. The discovery of angiotensin-converting enzyme 2 and the role of glucagon-like peptide-1 provide new potential therapeutic approaches for RAS modulation.
Article
Biochemistry & Molecular Biology
Joao Pedro Torres Guimaraes, Kalhara R. Menikdiwela, Theresa Ramalho, Luiz A. D. Queiroz, Nishan S. Kalupahana, Sonia Jancar, Latha Ramalingam, Joilson O. Martins, Naima Moustaid-Moussa
Summary: Impaired metabolic functions in diabetes and obesity are related to the renin-angiotensin system (RAS). This study found that treatment with captopril can improve the expression levels of RAS components, insulin signaling, and autophagy markers in muscle and liver of diabetic and obese mice, suggesting its potential utility in targeting insulin sensitivity and autophagy in these diseases.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Yukiko Yasuoka, Yuichiro Izumi, Takashi Fukuyama, Hideki Inoue, Tomomi Oshima, Taiga Yamazaki, Takayuki Uematsu, Noritada Kobayashi, Yoshitaka Shimada, Yasushi Nagaba, Masashi Mukoyama, Yuichi Sato, Jeff M. Sands, Katsumasa Kawahara, Hiroshi Nonoguchi
Summary: The kidney is the main site of erythropoietin production in the body. Research has shown that angiotensin II can stimulate erythropoietin production in the kidney, regulating erythropoietin production through the renin-angiotensin-aldosterone system (RAS).
Article
Chemistry, Physical
Anna Chachaj-Brekiesz, Anita Wnetrzak, Jan Kobierski, Aneta D. Petelska, Patrycja Dynarowicz-Latka
Summary: Cholesterol oxidation products, or oxysterols, have both negative and positive effects on biological processes. Their structure plays a crucial role in their physiological activity. This study focuses on how introducing a hydroxyl group at specific positions on the cholesterol skeleton affects the organization of the resulting molecules. By using various techniques, including Langmuir monolayer, microscopic, spectroscopic, and theoretical calculations, the researchers found that the introduction of a hydroxyl group at C(24) leads to stable monolayers, while introduction at C(25) and C(27) results in phase transition from monolayers to bilayer structures. The hydrogen bonding between adjacent oxysterol molecules is responsible for this transition.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)
Article
Medicine, Research & Experimental
Hai-Feng Zhang, Xiang Gao, Xuan Wang, Xin Chen, Yu Huang, Lang Wang, Zhou-Wei Xu
Summary: The passage discusses the relationship between the occurrence and development of hepatocellular carcinoma and various pathophysiological processes and cytokines, as well as the role of the renin-angiotensin system in HCC.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Peripheral Vascular Disease
Dominique M. Bovee, Liwei Ren, Estrellita Uijl, Marian C. Clahsen-van Groningen, Richard van Veghel, Ingrid M. Garrelds, Oliver Domenig, Marko Poglitsch, Ivan Zlatev, Jae B. Kim, Stephen Huang, Lauren Melton, Xifeng Lu, Ewout J. Hoorn, Don Foster, A. H. Jan Danser
Summary: AGT siRNA demonstrates blood pressure-lowering and renal protective effects in hypertensive chronic kidney disease, independently of blood pressure, mainly through suppression of renal Ang II formation from liver-derived AGT.
Article
Multidisciplinary Sciences
Kwang Min Kim, Ji-Hye Roh, Sangjin Lee, Jeong-Hyun Yoon
Summary: The study found no significant association between RAS inhibitors (RASi) use and the development or progression of non-alcoholic fatty liver disease (NAFLD) overall, but suggested a potential benefit in reducing the risk among individuals who are obese or have normal fasting plasma glucose levels.
SCIENTIFIC REPORTS
(2021)
Correction
Biochemistry & Molecular Biology
Holger Hengel, Rebecca Buchert, Marc Sturm, Tobias B. Haack, Yvonne Schelling, Muhammad Mahajnah, Rajech Sharkia, Abdussalam Azem, Ghassan Balousha, Zaid Ghanem, Mohammed Falana, Osama Balousha, Suhail Ayesh, Reinhard Keimer, Werner Deigendesch, Jimmy Zaidan, Hiyam Marzouqa, Peter Bauer, Ludger Schols
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Clinical Neurology
Holger Hengel, Peter Martus, Jennifer Faber, Hector Garcia-Moreno, Nita Solanky, Paola Giunti, Thomas Klockgether, Kathrin Reetz, Bart P. van de Warrenburg, Luis Pereira de Almeida, Magda M. Santana, Cristina Januario, Patrick Silva, Andreas Thieme, Jon Infante, Jeroen de Vries, Manuela Lima, Ana F. Ferreira, Khalaf Bushara, Heike Jacobi, Chiadi Onyike, Jeremy D. Schmahmann, Jeannette Huebener-Schmid, Matthis Synofzik, Ludger Schoels
Summary: The study found that patients with SCA3 had lower levels of physical activity and alcohol consumption compared to controls. Less physical activity and alcohol abstinence were associated with more severe disease, but did not affect disease progression rates or age of onset.
MOVEMENT DISORDERS
(2022)
Article
Clinical Neurology
Tim W. Rattay, Maximilian Voelker, Maren Rautenberg, Christoph Kessler, Isabel Wurster, Natalie Winter, Tobias B. Haack, Tobias Lindig, Holger Hengel, Matthis Synofzik, Rebecca Schule, Peter Martus, Ludger Schoels
Summary: This study explores early changes in the most common subtype of hereditary spastic paraplegia, SPG4, and identifies subclinical markers of disease activity in the prodromal stage. The findings suggest that certain clinical signs, such as increased reflexes and muscle weakness, may be more frequent in individuals who carry the genetic mutation associated with SPG4.
Article
Medicine, Research & Experimental
Stefan Hauser, Jacob Helm, Melanie Kraft, Milena Korneck, Jeannette Huebener-Schmid, Ludger Schoels
Summary: Spinocerebellar ataxia type 3 (SCA3) is caused by an expanded polyglutamine stretch in ataxin-3. Researchers have identified ASOs that can effectively suppress both mutant and wild-type ataxin-3 expression, as well as an ASO that selectively reduces levels of mutant ataxin-3 while sparing wild-type expression. This study demonstrates the feasibility and long-lasting effects of allele-specific lowering of poly(Q)-expanded ataxin-3 using selective ASOs in a human cell culture model genetically identical to SCA3 patients.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Article
Clinical Neurology
Afshin Saffari, Melanie Kellner, Catherine Jordan, Helena Rosengarten, Alisa Mo, Bo Zhang, Oleksandr Strelko, Sonja Neuser, Marie Y. Davis, Nobuaki Yoshikura, Naonobu Futamura, Tomoya Takeuchi, Shin Nabatame, Hiroyuki Ishiura, Shoji Tsuji, Huda Shujaa Aldeen, Elisa Cali, Clarissa Rocca, Henry Houlden, Stephanie Efthymiou, Birgit Assmann, Grace Yoon, Bianca A. Trombetta, Pia Kivisakk, Florian Eichler, Haitian Nan, Yoshihisa Takiyama, Alessandra Tessa, Filippo M. Santorelli, Mustafa Sahin, Craig Blackstone, Edward Yang, Rebecca Schuele, Darius Ebrahimi-Fakhari
Summary: This study delineates the clinical, neuroimaging, and molecular features of ZFYVE26-associated hereditary spastic paraplegia (HSP-ZFYVE26) patients. Most patients present with motor and/or speech delay, progressive spasticity, and extrapyramidal movement disorders. Elevated plasma neurofilament light chain levels correlate with disease severity.
Article
Genetics & Heredity
Adriana P. Rebelo, Ariel Ruiz, Maike F. Dohrn, Melanie Wayand, Amjad Farooq, Matt C. Danzi, Danique Beijer, Brooke Aaron, Jana Vandrovcova, Henry Houlden, Leslie Matalonga, Lisa Abreu, Guy Rouleau, Mehrdad A. Estiar, Liedewei Van de Vondel, Ziv Gan-Or, Jonathan Baets, Rebecca Schuele, Stephan Zuchner
Summary: This study reveals that FICD variants interfere with the regulation of BiP protein activity, leading to neurodegenerative diseases of upper and lower motor neurons. These findings have implications for the development of therapeutic strategies for motoneuron and proteotoxic stress-related diseases.
GENETICS IN MEDICINE
(2022)
Article
Clinical Neurology
Holger Hengel, Peter Martus, Jennifer Faber, Paola Giunit, Hector Garcia-Moreno, Nita Solanky, Thomas Klockgether, Kathrin Reetz, Bart P. van de Warrenburg, Magda M. Santana, Patrick Silva, Ines Cunha, Luis Pereira de Almeida, Dagmar Timmann, Jon Infante, Jeroen de Vries, Manuela Lima, Paula Pires, Khalaf Bushara, Heike Jacobi, Chiadi Onyike, Jeremy D. Schmahmann, Jeannette Hubener-Schmid, Matthis Synofzik, Ludger Schoels
Summary: This study reveals that non-motor symptoms such as sleep disturbance, restless legs syndrome, mild cognitive impairment, depression, bladder dysfunction, and pallhypesthesia are common among SCA3 patients and are significantly associated with disease severity and daily activities. Lifestyle factors like alcohol consumption, smoking, and physical activity may also be related to non-motor symptoms.
JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Thiago J. R. Rezende, Isaac M. Adanyeguh, Filippo Arrigoni, Benjamin Bender, Fernando Cendes, Louise A. Corben, Andreas Deistung, Martin Delatycki, Imis Dogan, Gary F. Egan, Sophia L. Goericke, Nellie Georgiou-Karistianis, Pierre-Gilles Henry, Diane Hutter, Neda Jahanshad, James M. Joers, Christophe Lenglet, Tobias Lindig, Alberto R. M. Martinez, Andrea Martinuzzi, Gabriella Paparella, Denis Peruzzo, Kathrin Reetz, Sandro Romanzetti, Ludger Schoels, Joerg B. Schulz, Matthis Synofzik, Sophia I. Thomopoulos, Paul M. Thompson, Dagmar Timmann, Ian H. Harding, Marcondes C. Franca
Summary: This study characterized cervical spinal cord structural damage in a large multisite cohort of Friedreich's ataxia (FRDA) patients. The results showed that FRDA patients had significantly reduced cross-sectional area (CSA) and increased eccentricity in the cervical spinal cord compared to control subjects. The CSA had significant correlations with disease severity, while eccentricity did not. Subgroup analyses revealed abnormal CSA and eccentricity at all disease stages, with CSA appearing to decrease progressively and eccentricity remaining stable over time.
MOVEMENT DISORDERS
(2023)
Article
Clinical Neurology
Alisa Mo, Afshin Saffari, Melanie Kellner, Marion Dobler-Neumann, Catherine Jordan, Siddharth Srivastava, Bo Zhang, Mustafa Sahin, John K. Fink, Linsley Smith, Jennifer E. Posey, Katharine E. Alter, Camilo Toro, Craig Blackstone, Ariane G. Soldatos, Michelle Christie, Rebecca Schule, Darius Ebrahimi-Fakhari
Summary: This study delineates the genotypic and phenotypic spectrum of children with de novo hereditary spastic paraplegia (HSP)-SPAST. The results confirm that de novo variants in SPAST lead to a severe and complex form of HSP that is different from classic familial pure HSP-SPAST. Clinicians should consider this syndrome in the differential diagnosis for cerebral palsy.
MOVEMENT DISORDERS
(2022)
Article
Chemistry, Analytical
Ece Aydin, Malgorzata Cebo, Justyna Mielnik, Hardy Richter, Rebecca Schuele, Adrian Sievers-Engler, Piotr Mlynarz, Michael Laemmerhofer
Summary: Endocannabinoids are endogenous lipids that act as neuromodulators through cannabinoid receptors. This study developed a sensitive UHPLC-MS/MS method for the analysis of trace levels of 7 endocannabinoids in cerebrospinal fluid samples. The method demonstrated excellent sensitivity, accuracy, and reliability, and was used to quantify endocannabinoids in 118 human cerebrospinal fluid samples. Differences in endocannabinoid concentrations were observed between patients with CNS infection and controls.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2023)
Editorial Material
Biochemistry & Molecular Biology
Annemieke Aartsma-Rus, Willeke van Roon-Mom, Marlen Lauffer, Christine Siezen, Britt Duijndam, Tineke Coenen-de Roo, Rebecca Schuele, Matthis Synofzik, Holm Graessner
Summary: Splice-modulating antisense oligonucleotides (ASOs) provide treatment options for rare neurological diseases with rare mutations, and patient-specific ASOs need to be developed. The 1 Mutation 1 Medicine (1M1M) and Dutch Center for RNA Therapeutics (DCRT) aim to develop and treat eligible patients with patient-specific ASOs in Europe and the Netherlands, respectively, under a named patient setting.
Article
Neurosciences
Vilma Alanko, Adhara Gaminde-Blasco, Tania Quintela-Lopez, Raul Loera-Valencia, Alina Solomon, Ingemar Bjorkhem, Angel Cedazo-Minguez, Silvia Maioli, Graziella Tabacaru, Maria Latorre-Leal, Carlos Matute, Miia Kivipelto, Elena Alberdi, Anna Sandebring-Matton
Summary: Oxidized cholesterol metabolite 27-hydroxycholesterol (27-OH) is a potential link between hypercholesterolemia and neurodegenerative diseases as it can cross the blood-brain barrier. This study found that high levels of 27-OH can impact oligodendrocyte function and contribute to the disconnection of neural networks in neurodegenerative diseases.
Correction
Clinical Neurology
Holger Hengel, Peter Martus, Jennifer Faber, Paola Giunti, Hector Garcia-Moreno, Nita Solanky, Thomas Klockgether, Kathrin Reetz, Bart P. van de Warrenburg, Magda M. Santana, Patrick Silva, Ines Cunha, Luis Pereira de Almeida, Dagmar Timmann, Jon Infante, Jeroen de Vries, Manuela Lima, Paula Pires, Khalaf Bushara, Heike Jacobi, Chiadi Onyike, Jeremy D. Schmahmann, Jeannette Huebener-Schmid, Matthis Synofzik, Ludger Schoels
JOURNAL OF NEUROLOGY
(2023)
Article
Neurosciences
Maresa Buchholz, Niklas Weber, Anika Raedke, Jennifer Faber, Tanja Schmitz-Huebsch, Heike Jacobi, Feng Xie, Thomas Klockgether, Bernhard Michalowsky
Summary: The study confirmed an acceptable, reliable, valid, and responsive EQ-5D-3L in SCA patients, measuring HRQoL adequately, besides well-established clinical instruments.