Review
Neurosciences
Naif H. Ali, Hayder M. Al-Kuraishy, Ali I. Al-Gareeb, Ali K. Albuhadily, Rabab S. Hamad, Athanasios Alexiou, Marios Papadakis, Hebatallah M. Saad, Gaber El-Saber Batiha
Summary: This article discusses the pathophysiology of depression and the role of the brain renin-angiotensin system (RAS) in it. It is found that angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may be effective in the treatment of depression. By regulating serotonin, brain-derived neurotrophic factor, mitochondrial dysfunction, oxidative stress, and neuroinflammation, these drugs can ameliorate the pathophysiology of depression.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Review
Cell Biology
Filipa Gouveia, Antoni Camins, Miren Ettcheto, Joana Bicker, Amilcar Falcao, M. Teresa Cruz, Ana Fortuna
Summary: Alzheimer's disease (AD) is a neurodegenerative disease that is characterized by Tau hyperphosphorylation and A beta deposits. Recent scientific evidence suggests that age-related vascular alterations and cardiovascular risk factors play a role in the development of AD. Drugs targeting the Renin Angiotensin System (RAS) have the potential to delay AD development due to their effects on brain RAS. The ACE 1/Ang II/AT1R axis in AD is believed to have detrimental effects, while the alternative axis ACE 1/Ang II/AT2R; ACE 2/Ang (1 7)/MasR; Ang IV/AT4R (IRAP) seems to have beneficial effects on memory and cognition. Retrospective studies and pre-clinical studies support the therapeutic potential of RAS drugs for AD.
AGEING RESEARCH REVIEWS
(2022)
Review
Oncology
Huirong Jiang, Zongguang Tai, Zhongjian Chen, Quangang Zhu, Leilei Bao
Summary: The renin-angiotensin system plays a crucial role in the development of malignant tumors, and long-term use of RAS inhibitors can lower the risk of cancer. Blocking RAS has been shown to inhibit tumor growth, metastasis, and angiogenesis in malignant tumors.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Article
Urology & Nephrology
Maria Jose Soler, Aida Ribera, Josep R. Marsal, Ana Belen Mendez, Mireia Andres, Maria Antonia Azancot, Gerard Oristrell, Leonardo Mendez-Boo, Jordana Cohen, Jose A. Barrabes, Ignacio Ferreira-Gonzalez
Summary: In a cohort study of HTN patients, it was found that the use of ACEi/ARBs reduced the risk of COVID-19 infection without increasing disease severity.
CLINICAL KIDNEY JOURNAL
(2022)
Review
Neurosciences
Bernardo H. M. Correa, Luca Becari, Marco Antonio Peliky Fontes, Ana Cristina Simoes-E-Silva, Lucas M. Kangussu
Summary: This comprehensive review summarizes the current knowledge on the participation of renin-angiotensin system (RAS) components in different adverse environmental stimuli stressors. It explores the effects of the activation of the classical RAS axis and the counter-regulatory axis on stress-related cardiovascular, endocrine, and behavioral responses. Pharmacological modulation in both axes shows promising perspectives for stress-related disorders treatment, with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers being potential candidates.
CURRENT NEUROPHARMACOLOGY
(2022)
Review
Physiology
Simon B. Gressens, Georges Leftheriotis, Jean-Claude Dussaule, Martin Flamant, Bernard I. Levy, Emmanuelle Vidal-Petiot
Summary: This review explores the risks of using RAAS blockers for patients with cardiovascular comorbidities during the COVID-19 pandemic, investigates the impact of RAAS blockers on viral cell entry, and discusses how to maintain the balance between ACE2 and ACE and the effect of RAAS blockers on the course and prognosis of COVID-19 treatment.
FRONTIERS IN PHYSIOLOGY
(2021)
Review
Critical Care Medicine
Daniel H. Baron, Olivia A. Skrobot, Jennifer C. Palmer, Kanchan Sharma, Patrick G. Kehoe
Summary: This review investigates the potential of the renin-angiotensin system (RAS) as a treatment pathway for traumatic brain injury (TBI) in adults. The study found that angiotensin-receptor blockers, especially candesartan, showed positive outcomes in improving neurological function in pre-clinical studies. However, further research on the effect of regulatory-RAS targeting drugs is needed.
JOURNAL OF NEUROTRAUMA
(2022)
Article
Medicine, General & Internal
Aimin Yang, Hongjiang Wu, Eric S. H. Lau, Mai Shi, Baoqi Fan, Alice Pik-Shan Kong, Ronald Ching -Wan Ma, Andrea On-Yan Luk, Juliana Chung-Ngor Chan, Elaine Chow
Summary: The study found that RAS inhibitors are associated with lower cancer risk in type 2 diabetes patients, with better effects for users of ARBs. These results suggest that RASi may have broader benefits for patients with diabetes.
Article
Oncology
Driss Laghlam, Anis Chaba, Matthias Tarneaud, Julien Charpentier, Jean-Paul Mira, Frederic Pene, Clara Vigneron
Summary: This retrospective study aimed to assess the prognostic impact of renin-angiotensin system blockers (RABs) in critically ill cancer patients. The results showed that the use of angiotensin-receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEis) was associated with improved in-ICU survival and one-year survival. Cellular evidence supports the beneficial impact of RABs on the survival rates of solid tumor patients.
Review
Biochemistry & Molecular Biology
Fernanda Rocha Chaves Moreira, Tiago Almeida de Oliveira, Nadia Eliza Ramos, Maria Augusta Duarte Abreu, Ana Cristina Simoes E Silva
Summary: The renin-angiotensin system (RAS) plays a crucial role in the pathogenesis of rheumatoid arthritis (RA) and osteoarthritis (OA), with the classical and counter-regulatory pathways modulating inflammation and tissue damage. Inflammation and angiogenesis are facilitated by classical RAS activation, while osteopenia contributes to joint dysfunction. Up-regulated osteoclastogenesis and down-regulated osteoblastogenesis are associated with the classical RAS axis activation. Studies on the use of angiotensin receptor blockers (ARBs), angiotensin converting enzyme inhibitors (ACEi) and renin inhibitors in RA have shown promising results.
MOLECULAR BIOLOGY REPORTS
(2021)
Review
Pharmacology & Pharmacy
Hanne Salmenkari, Riitta Korpela, Heikki Vapaatalo
Summary: Inflammatory bowel diseases require new treatment options to control inflammation and fibrosis, and RAS inhibitors may be a cost-effective and effective alternative. While animal studies have shown the efficacy of RAS inhibitors in colitis, human data are still limited. Retrospective studies indicate that IBD patients using RAS inhibitors have a milder disease course and fewer hospitalizations.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2021)
Article
Oncology
Marcin Zeman, Wladyslaw Skalba, Agata Malgorzata Wilk, Alexander Jorge Cortez, Adam Maciejewski, Agnieszka Czarniecka
Summary: The use of ARBs instead of ACEIs may improve the outcome of the combined therapy for rectal cancer patients with associated hypertension.
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
Biochemistry & Molecular Biology
Sam Siljee, Bridget Milne, Helen D. Brasch, Nicholas Bockett, Josie Patel, Paul F. Davis, Andrew Kennedy-Smith, Tinte Itinteang, Swee T. Tan
Summary: This study demonstrated the expression of PRR, ACE2, and AT(2)R by the CSCs within RCCC. Further studies may lead to novel therapeutic targeting of CSCs by manipulation of the RAS in the treatment of this aggressive cancer.
Review
Pharmacology & Pharmacy
Gregory L. Hundemer, Manish M. Sood
Summary: RAAS inhibitors are evidence-based treatments for various conditions, but can lead to hyperkalemia, which increases the risk for cardiovascular events. Managing hyperkalemia while maintaining the benefits of RAAS inhibitors is essential to prevent adverse outcomes.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Transplantation
Peter Rossing
Summary: The KDIGO guideline on Diabetes Management in Chronic Kidney Disease provides comprehensive care recommendations for patients with diabetes and CKD, focusing on glycemic control and new treatment options.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2023)
Article
Peripheral Vascular Disease
Rajiv Agarwal, Luis M. Ruilope, Gema Ruiz-Hurtado, Hermann Haller, Roland E. Schmieder, Stefan D. Anker, Gerasimos Filippatos, Bertram Pitt, Peter Rossing, Marc Lambelet, Christina Nowack, Peter Kolkhof, Amer Joseph, George L. Bakris
Summary: Finerenone, a selective nonsteroidal mineralocorticoid receptor antagonist, was found to reduce 24-hour, daytime, and nighttime systolic blood pressure in patients with chronic kidney disease and type 2 diabetes.
JOURNAL OF HYPERTENSION
(2023)
Article
Cardiac & Cardiovascular Systems
Gerasimos Filippatos, Stefan D. Anker, Phyllis August, Andrew J. S. Coats, James L. Januzzi, Boris Mankovsky, Peter Rossing, Luis M. Ruilope, Bertram Pitt, Pantelis Sarafidis, John R. Teerlink, Chris J. Kapelios, Martin Gebel, Meike Brinker, Amer Joseph, Andrea Lage, George Bakris, Rajiv Agarwal
Summary: This study investigated the causes of mortality in patients with chronic kidney disease and type 2 diabetes. The findings showed that Finerenone significantly reduced the risk of all-cause and cardiovascular mortality in T2D patients across different stages of CKD, and particularly in preventing cardiovascular-related deaths and sudden cardiac death.
EUROPEAN HEART JOURNAL-CARDIOVASCULAR PHARMACOTHERAPY
(2023)
Article
Endocrinology & Metabolism
Viktor Rotbain Curovic, Nete Tofte, Morten Lindhardt, Katarina Adamova, Stephan J. L. Bakker, Joachim Beige, Joline W. J. Beulens, Andreas L. Birkenfeld, Gemma Currie, Christian Delles, Ingo Dimos, Lidmila Francova, Marie Frimodt-Moller, Peter Girman, Ruediger Goeke, Tine W. Hansen, Tereza Havrdova, Adriaan Kooy, Gozewijnw D. Laverman, Harald Mischak, Gerjan Navis, Giel Nijpels, Marina Noutsou, Alberto Ortiz, Aneliya Parvanova, Frederik Persson, John R. Petrie, Piero L. Ruggenenti, Femke Rutters, Ivan Rychlik, Justyna Siwy, Goce Spasovski, Marijn Speeckaert, Matias Trillini, Petra Zuerbig, Heiko von der Leyen, Peter Rossing
Summary: This study examines the relationship between baseline diabetic retinopathy (DR) and the risk of developing microalbuminuria, kidney function decline, and cardiovascular events (CVEs) in type 2 diabetes patients. The results show that the presence of DR is associated with an increased risk of developing microalbuminuria and CVEs, but not kidney function decline.
JOURNAL OF DIABETES AND ITS COMPLICATIONS
(2023)
Article
Endocrinology & Metabolism
Jens Christian Laursen, Christian Stevns Hansen, Marco Bordino, Marie Frimodt-Moller, Tine Willum Hansen, Luciano Bernardi, Per-Henrik Groop, Peter Rossing
Summary: This study explored the association between baroreflex sensivity and blood oxygen saturation (SpO2) in type 1 diabetes and various degrees of microvascular disease. It was found that higher baroreflex sensitivity was associated with higher SpO2 in type 1 diabetes. Compared with non-diabetic controls, type 1 diabetes patients had lower baroreflex sensitivity and lower SpO2. Therefore, hypoxia could be a therapeutic target in type 1 diabetes.
JOURNAL OF DIABETES AND ITS COMPLICATIONS
(2023)
Article
Multidisciplinary Sciences
Roderick C. Slieker, Louise A. Donnelly, Elina Akalestou, Livia Lopez-Noriega, Rana Melhem, Aysim Gunes, Frederic Abou Azar, Alexander Efanov, Eleni Georgiadou, Hermine Muniangi-Muhitu, Mahsa Sheikh, Giuseppe N. Giordano, Mikael Akerlund, Emma Ahlqvist, Ashfaq Ali, Karina Banasik, Soren Brunak, Marko Barovic, Gerard A. Bouland, Frederic Burdet, Mickael Canouil, Iulian Dragan, Petra J. M. Elders, Celine Fernandez, Andreas Festa, Hugo Fitipaldi, Phillippe Froguel, Valborg Gudmundsdottir, Vilmundur Gudnason, Mathias J. Gerl, Amber A. van der Heijden, Lori L. Jennings, Michael K. Hansen, Min Kim, Isabelle Leclerc, Christian Klose, Dmitry Kuznetsov, Dina Mansour Aly, Florence Mehl, Diana Marek, Olle Melander, Anne Niknejad, Filip Ottosson, Imre Pavo, Kevin Duffin, Samreen K. Syed, Janice L. Shaw, Over Cabrera, Timothy J. Pullen, Kai Simons, Michele Solimena, Tommi Suvitaival, Asger Wretlind, Peter Rossing, Valeriya Lyssenko, Cristina Legido Quigley, Leif Groop, Bernard Thorens, Paul W. Franks, Gareth E. Lim, Jennifer Estall, Mark Ibberson, Joline W. J. Beulens, Leen M't Hart, Ewan R. Pearson, Guy A. Rutter
Summary: We identified biomarkers for disease progression in type 2 diabetes cohorts, including metabolites, lipids, and proteins. Various substances such as homocitrulline, isoleucine, 2-aminoadipic acid, triacylglycerol species, and sphingomyelin 42:2;2 levels were found to predict faster progression towards insulin requirement. Proteins like GDF15/MIC-1, IL-18Ra, CRELD1, NogoR, FAS, and ENPP7 were associated with faster progression, while others like SMAC/DIABLO, SPOCK1, and HEMK2 predicted slower progression rates. The findings also suggested possible disease mechanisms and potential therapeutic avenues to slow diabetes progression.
NATURE COMMUNICATIONS
(2023)
Article
Medicine, General & Internal
Marie Moller, Rikke Borg, Iain Bressendorff, Lisbeth N. Fink, Eva Gravesen, Karina Haar Jensen, Torben Hansen, Dorrit Krustrup, Frederik Persson, Peter Rossing, Frederikke E. Sembach, Anne C. B. Thuesen, Ditte Hansen
Summary: Diabetic kidney disease is a severe complication of diabetes, and a kidney biopsy is the only way to accurately diagnose it. This study aims to investigate the prevalence of diabetic kidney disease in individuals with type 2 diabetes and explore potential targets for individualized treatment through in-depth molecular analysis of kidney tissue samples.
Article
Endocrinology & Metabolism
Mikkel Jurgens, Morten Schou, Philip Hasbak, Andreas Kjaer, Emil Wolsk, Bo Zerahn, Niels H. Brandt-Jacobsen, Peter Gaede, Peter Rossing, Jens Faber, Silvio E. Inzucchi, Finn Gustafsson, Caroline Kistorp
Summary: Empagliflozin has been found to reduce measured glomerular filtration rate (mGFR), estimated plasma volume (PV), and estimated extracellular volume (ECV) in patients with type 2 diabetes (T2D) and high risk of cardiovascular events. The 13-week randomized controlled trial showed a decrease in mGFR, ECV, and PV with the use of the drug.
DIABETES OBESITY & METABOLISM
(2023)
Article
Endocrinology & Metabolism
Viktor Rotbain Curovic, Morten B. Houlind, Marjolein Y. A. M. Kroonen, Niels Jongs, Emilie H. Zobel, Tine W. Hansen, Juliette Tavenier, Jesper Eugen-Olsen, Gozewijn D. Laverman, Adriaan Kooy, Frederik Persson, Peter Rossing, Hiddo J. L. Heerspink
Summary: The effect of four different drug classes on suPAR levels in people with type 1 and type 2 diabetes was evaluated. The study showed no overall effect of the drugs on suPAR levels, but individualized treatment significantly reduced suPAR levels.
DIABETES OBESITY & METABOLISM
(2023)
Letter
Endocrinology & Metabolism
Jens Christian Laursen, Viktor Rotbain Curovic, Marjolein Y. A. M. Kroonen, Niels Jongs, Emilie H. Zobel, Tine W. Hansen, Marie Frimodt-Moller, Gozewijn D. Laverman, Adriaan Kooy, Frederik Persson, Hiddo J. L. Heerspink, Christian Stevns Hansen, Peter Rossing
DIABETES OBESITY & METABOLISM
(2023)
Article
Endocrinology & Metabolism
Ninna Hahn Tougaard, Tine Willum Hansen, Peter Rossing
Summary: Vitamin D deficiency may be a risk marker for cardiovascular events and heart failure in both type 1 and type 2 diabetes, but not for microvascular complications or all-cause mortality.
JOURNAL OF DIABETES AND ITS COMPLICATIONS
(2023)
Article
Chemistry, Medicinal
Mayra Alejandra Jaimes Campos, Ivan Andujar, Felix Keller, Gert Mayer, Peter Rossing, Jan A. Staessen, Christian Delles, Joachim Beige, Griet Glorieux, Andrew L. Clark, William Mullen, Joost P. Schanstra, Antonia Vlahou, Kasper Rossing, Karlheinz Peter, Alberto Ortiz, Archie Campbell, Frederik Persson, Agnieszka Latosinska, Harald Mischak, Justyna Siwy, Joachim Jankowski
Summary: In this study, we used urinary peptidomic classifiers to predict renal or cardiovascular events in a cohort of 5585 subjects. The results showed significant prediction of events for heart failure, coronary artery disease, and chronic kidney disease. We implemented in silico treatment to simulate changes in peptide abundance based on commonly used interventions, and the proteomic classifiers indicated the individual benefits of specific interventions on a personalized level.
Article
Urology & Nephrology
Yeli Wang, Ogechi M. Adingwupu, Michael G. Shlipak, Alessandro Doria, Michelle M. Estrella, Marc Froissart, Vilmundur Gudnason, Anders Grubb, Roberto Kalil, Michael Mauer, Peter Rossing, Jesse Seegmiller, Josef Coresh, Andrew S. Levey, Lesley A. Inker
Summary: This study found that the combination of cystatin C and creatinine provides the most accurate estimates of glomerular filtration rate, especially when eGFRcr and eGFRcys are discordant.
Review
Urology & Nephrology
Varin Vinje, Tobias Bomholt, Peter Rossing, Carsten Lundby, Peter Oturai, Mads Hornum
Summary: This paper reviews techniques for assessing patient blood volume to enhance our understanding of the physiological effects of SGLT2 inhibitors. Radioisotope, ICG dye, and carbon monoxide dilution techniques can provide direct estimates of erythrocyte and plasma volume, with ICG dye and carbon monoxide methods being more suitable for repeated assessment.
Review
Urology & Nephrology
Tobias Bomholt, Dea Kofod, Kirsten Norgaard, Peter Rossing, Bo Feldt-Rasmussen, Mads Hornum
Summary: CGM provides more detailed measurements of mean sensor glucose, glucose variability, and time in ranges, which can overcome the limitations of HbA1c in dialysis patients. It has the potential to improve glycemic control and detect hypoglycemia. However, the long-term use of CGM in the dialysis population has not been evaluated and practical burden and cost may be a limitation.