Article
Cardiac & Cardiovascular Systems
Masayoshi Kukida, Naofumi Amioka, Dien Ye, Hui Chen, Jessica J. Moorleghen, Ching-Ling Liang, Deborah A. Howatt, Yuriko Katsumata, Motoko Yanagita, Hisashi Sawada, Alan Daugherty, Hong S. Lu
Summary: This study investigated the role of the renal renin-angiotensin system (RAS) in atherosclerosis development. While whole body inhibition of the RAS had significant effects, specific manipulation of RAS components in renal proximal tubule cells had no impact on atherosclerosis in either sex. These findings suggest that the site of RAS activity influencing lesion formation is still unknown.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Article
Endocrinology & Metabolism
Amanda da Silva Chaves, Nathalia Santos Magalhaes, Daniella Bianchi Reis Insuela, Patricia Machado Rodrigues E Silva, Marco Aurelio Martins, Vinicius Frias Carvalho
Summary: This study investigates the role of the renin-angiotensin system (RAS) in the overproduction of corticosterone in diabetic mice. The results suggest that inhibition of angiotensin synthesis and AT(1) receptor activity can reduce corticosterone levels in diabetic mice. Furthermore, the protective effect of Olmesartan on corticosterone overproduction in diabetic mice depends on both AT(1) receptor blockade and AT(2) receptor activation.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Medicine, General & Internal
Ke Ma, Zi-Run Zheng, Yu Meng
Summary: Chronic kidney disease (CKD) and Alzheimer's disease (AD) are common in the aging population, but the connection between them is still unclear. This review shows that the development of CKD may contribute to AD, especially through the renin-angiotensin system (RAS).
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Endocrinology & Metabolism
Johannes J. Kovarik, Christopher C. Kaltenecker, Oliver Domenig, Marlies Antlanger, Marko Poglitsch, Chantal Kopecky, Marcus D. Saemann
Summary: In this study, the effects of combined MRA eplerenone and ACEi therapy on key RAAS effectors in CKD patients were examined. The results showed that eplerenone treatment led to global RAAS activation while significantly increasing the alternative RAAS effector Ang-(1-7).
Article
Endocrinology & Metabolism
Edoardo Biancalana, Giovanni Ceccarini, Silvia Magno, Valerio Ortenzi, Domenico Giannese, Ferruccio Santini, Anna Solini
Summary: A 40-year-old woman with acquired partial lipodystrophy, type 2 diabetes, and essential hypertension complicated by chronic kidney disease and proteinuria showed a significant reduction in proteinuria after adding SGLT2 inhibitors to her treatment regimen.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Endocrinology & Metabolism
Marlies Antlanger, Oliver Domenig, Christopher C. Kaltenecker, Johannes J. Kovarik, Vincent Rathkolb, Martin M. Mueller, Elisabeth Schwaiger, Manfred Hecking, Marko Poglitsch, Marcus D. Saeemann, Chantal Kopecky
Summary: This study investigated the molecular RAS dynamics in patients with chronic kidney disease treated with SGLT-2i empagliflozin on top of ACEi. The results showed that in patients with type 2 diabetes, the combination of SGLT-2i and ACEi led to changes in RAS regulation, including an increase in beneficial angiotensin-(1-7) levels. However, no significant effect was observed in patients with CKD without diabetes.
DIABETES OBESITY & METABOLISM
(2022)
Review
Cardiac & Cardiovascular Systems
Sarah M. Nwia, Ana Paula O. Leite, Xiao Chun Li, Jia Long Zhuo
Summary: Cardiovascular disease demonstrates significant biological sex differences, allowing for tailored approaches to prevention and treatment. Hypertension, a major risk factor for various diseases, affects a significant percentage of the American population. Women have lower rates of hypertension during reproductive years, but this protection diminishes after menopause. Treatment-resistant hypertension remains a challenge, suggesting unknown mechanisms in blood pressure regulation. Understanding the genetic and hormonal differences in hypertension can lead to sex-specific treatments and improved outcomes.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Letter
Medicine, General & Internal
Robert C. Speth
Summary: The article does not differentiate between ACE inhibitor therapy and ARB therapy in advanced CKD. The mechanisms of action of ACE inhibitors and ARBs differ substantially, with varying effects on renal function.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Sebastian Andone, Zoltan Bajko, Anca Motataianu, Smaranda Maier, Laura Barcutean, Rodica Balasa
Summary: This article reviews the role of the renin-angiotensin system in stroke neuroprotection. The effects of the renin-angiotensin system on receptors were observed, and the neuroprotective properties seem to be independent of the blood pressure reduction mechanism.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Peripheral Vascular Disease
Shinya Taguchi, Kengo Azushima, Takahiro Yamaji, Toru Suzuki, Eriko Abe, Shohei Tanaka, Keigo Hirota, Shunichiro Tsukamoto, Ryutaro Morita, Ryu Kobayashi, Sho Kinguchi, Akio Yamashita, Hiromichi Wakui, Kouichi Tamura
Summary: The combination of ATRAP deletion and Ang II stimulation accelerates the development of DKD in STZ-induced diabetic C57BL/6 mice that are resistant to kidney injury, which may be associated with intrarenal RAS overactivation.
HYPERTENSION RESEARCH
(2023)
Article
Hematology
Hisashi Sawada, Satoko Ohno-Urabe, Dien Ye, Michael K. Franklin, Jessica J. Moorleghen, Deborah A. Howatt, Adam E. Mullick, Alan Daugherty, Hong S. Lu
Summary: This study found that inhibition of angiotensin II action or production of the renin-angiotensin system does not attenuate BAPN-induced thoracic aortopathies in mice.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2022)
Article
Cell Biology
Jorge F. Giani, Luciana C. Veiras, Justin Z. Y. Shen, Ellen A. Bernstein, DuoYao Cao, Derick Okwan-Duodu, Zakir Khan, Romer A. Gonzalez-Villalobos, Kenneth E. Bernstein
Summary: Renal angiotensin-converting enzyme (ACE) plays a key role in the development of various kidney diseases, particularly hypertension. Studies suggest that ACE may mediate its effects through mechanisms independent of Ang II conversion, involving other substrates.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2021)
Article
Geriatrics & Gerontology
Cedric Villain, Marie Metzger, Sophie Liabeuf, Aghiles Hamroun, Solene Laville, Nicolas Mansencal, Christian Combe, Denis Fouque, Luc Frimat, Christian Jacquelinet, Maurice Laville, Carole Ayav, Serge Briancon, Roberto Pecoits-Filho, Thierry Hannedouche, Benedicte Stengel, Ziad A. Massy
Summary: This study suggests that aging does not appear to modify the beneficial effects of RASi on major CKD outcomes or their potential adverse effects.
JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION
(2022)
Article
Endocrinology & Metabolism
Toshiyuki Yano, Satoshi Katano, Hidemichi Kouzu, Ryohei Nagaoka, Takuya Inoue, Yuhei Takamura, Tomoyuki Ishigo, Ayako Watanabe, Katsuhiko Ohori, Masayuki Koyama, Nobutaka Nagano, Takefumi Fujito, Ryo Nishikawa, Akiyoshi Hashimoto, Tetsuji Miura
Summary: In patients with chronic heart failure (CHF) and diabetes mellitus (DM), differences were observed in muscle mass, cardiovascular disease, hypertension prevalence, estimated glomerular filtration rate (eGFR), plasma renin activity (PRA), and other factors. Nutritional assessment, blood glucose levels, and renin-angiotensin system activation may be associated with muscle wasting in CHF patients with DM.
JOURNAL OF DIABETES
(2021)
Review
Immunology
Sizhu Gong, Fang Deng
Summary: Emotional disorders, such as depression and anxiety, have a significant impact on global morbidity. The renin-angiotensin system (RAS) plays a role in hypertension and emotional disorders, and elevated RAS activity is associated with depression and anxiety through neuroinflammation, stress, and oxidative stress. Blocking the RAS could potentially be a future treatment approach for anxiety and depression. The positive effects of RAS blockers on these disorders are reviewed, aiming to provide a promising target for novel medications and to improve the efficacy of current treatments independent of blood pressure management.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Mazher Mohammed, Dominique N. Johnson, Lei A. Wang, Scott W. Harden, Wanhui Sheng, Eliot A. Spector, Khalid Elsaafien, Michael Bader, U. Muscha Steckelings, Karen A. Scott, Charles J. Frazier, Colin Sumners, Eric G. Krause, Annette D. de Kloet
Summary: These studies use advanced techniques to investigate the role of AT2R-expressing neurons in the NTS in blood pressure regulation. Optogenetic stimulation of these neurons increases GABA release and blood pressure. Central activation of AT2R also reduces GABA-related gene expression and blunts pressor responses.
CARDIOVASCULAR RESEARCH
(2022)
Article
Peripheral Vascular Disease
Katja Grabowski, Laura Herlan, Anika Witten, Fatimunnisa Qadri, Andreas Eisenreich, Diana Lindner, Martin Schaedlich, Angela Schulz, Jana Subrova, Ketaki Nitin Mhatre, Uwe Primessnig, Ralph Plehm, Sophie van Linthout, Felicitas Escher, Michael Bader, Monika Stoll, Dirk Westermann, Frank R. Heinzel, Reinhold Kreutz
Summary: Through genetic models and mouse experiments, the study identified the importance of Cpxm2 in hypertension-mediated left ventricular hypertrophy and cardiac damage, and showed that the absence of Cpxm2 can effectively reduce these injuries.
HYPERTENSION RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Anna Haduch, Przemyslaw J. Danek, Wojciech Kuban, Renata Puklo, Natalia Alenina, Joanna Golebiowska, Piotr Popik, Michael Bader, Wladyslawa A. Daniel
Summary: The study indicates that aging and serotonin deficiency have sex-dependent effects on brain CYP2D in female rats, potentially negatively impacting neurotransmitter synthesis but benefiting neurosteroid metabolism.
NEUROCHEMISTRY INTERNATIONAL
(2022)
Article
Cardiac & Cardiovascular Systems
Yingqiu Cui, Mario Kassmann, Sophie Nickel, Chenglin Zhang, Natalia Alenina, Yoland Marie Anistan, Johanna Schleifenbaum, Michael Bader, Donald G. Welsh, Yu Huang, Maik Gollasch
Summary: This study demonstrates that myogenic arterial constriction requires G(q/11)-dependent signaling pathways of mechanoactivated AT1R but not G protein-independent, noncanonical pathways in smooth muscle cells.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2022)
Article
Multidisciplinary Sciences
Naozumi Araragi, Natalia Alenina, Michael Bader
Summary: This study investigates the behavioral effects of optogenetic stimulation on serotonergic neurons. The researchers found that optogenetic stimulation enhances locomotion even in mice that do not express the light-sensitive protein. This unspecific effect is likely caused by light leakage, which can be eliminated by using black dental cement mixed with carbon.
Letter
Biochemistry & Molecular Biology
Daniel Batlle, Vanessa Monteil, Elena Garreta, Luise Hassler, Jan Wysocki, Vasuretha Chandar, Robert E. Schwartz, Ali Mirazimi, Nuria Montserrat, Michael Bader, Josef M. Penninger
Article
Peripheral Vascular Disease
Scott Hoffmann, Linda Mullins, Sebastien Rider, Cara Brown, Charlotte B. Buckley, Adrienne Assmus, Ziwen Li, Mariana Sierra Beltran, Neil Henderson, Jorge del Pozo, Alexandre De Goes Martini, Maria Luisa S. Sequeira-Lopez, R. Ariel Gomez, John Mullins
Summary: This study reveals the evolution of renin cell function with terrestrial survival through the knockout of renin in zebrafish and mice.
Article
Medicine, Research & Experimental
Brian C. Belyea, Fang Xu, Margaret Wiltsie, Hayes Fountain, Jennifer Charlton, Agnes B. Fogo, Maria Luisa Soledad Sequeira-Lopez, Roberto Ariel Gomez
Summary: Polycystic kidney disease (PKD) is a genetic disorder characterized by enlarged kidneys, fluid-filled cysts, and end-stage kidney disease. This study reveals the crucial role of the Notch signaling pathway in the pathogenesis of PKD and suggests that targeting the Notch-Myc axis could be a potential therapeutic approach.
Article
Physiology
Vidya K. Nagalakshmi, Minghong Li, Xiuyin Liang, Silvia Medrano, Brian C. Belyea, R. Ariel Gomez, Maria Luisa S. Sequeira-Lopez
Summary: The study found that ureteral obstruction leads to significant changes in kidney renin expression, and the contribution of renin-producing cells (RPCs) and the cells of the renin lineage (CoRL) towards kidney damage and regeneration was elucidated. These findings suggest that CoRL play a role in the regeneration of the kidneys post-relief of obstruction.
Article
Peripheral Vascular Disease
Barbara M. Alexander, Andrew South, Phyllis August, Mariane P. Bertagnolli, Erin L. Ferranti, Justin J. Grobe, Emily S. Jones, Analia Loria, Basmah Safdar, Maria Luisa Soledad Sequeira-Lopez
Summary: There is growing interest in the long-term cardiovascular health of women with complicated pregnancies and their affected offspring. Antenatal risk factors such as preeclampsia increase the risk of hypertension and cardiovascular disease in both the mother and the offspring, but the underlying mechanisms are complex and not fully understood. The renin-angiotensin-aldosterone system plays a critical role in maternal-fetal health and the development of pregnancy complications, and understanding its programming during pregnancy is crucial for identifying at-risk individuals and developing effective therapies. Preclinical and translational research should adhere to best practices in accurately measuring components of this system to ensure reliable results.
Review
Peripheral Vascular Disease
Hiroki Yamaguchi, R. Ariel Gomez, Maria Luisa S. Sequeira-Lopez
Summary: During embryonic and neonatal life, renin cells contribute to the assembly and branching of the intrarenal arterial tree. In adult life, renin cells are confined to the tips of the renal arterioles, releasing renin to control blood pressure and fluid-electrolyte homeostasis. Mechanisms such as β-adrenergic stimulation, macula densa signaling, and renin baroreceptor control the release of renin.
Letter
Cardiac & Cardiovascular Systems
Alexandre G. Martini, Jason P. Smith, Silvia Medrano, Gal Finer, Nathan C. Sheffield, Maria Luisa S. Sequeira-Lopez, R. Ariel Gomez
CIRCULATION RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Priyavathi Sureshkumar, Robson Augusto Souza dos Santos, Natalia Alenina, Stefan Mergler, Michael Bader
Summary: The G protein-coupled receptor MAS is the receptor for the endogenous ligand Angiotensin (Ang)-(1-7). This paper demonstrates the importance of MAS signaling in developing novel therapeutics for cardiovascular diseases. Ang-(1-7) induces calcium influx in MAS-transfected HEK293 cells, which is dependent on plasma membrane Ca2+ channels, phospholipase C, and protein kinase C. The study also reveals that MAS utilizes non-selective transient receptor potential channels (TRPs) for calcium entry.
Article
Physiology
Jesus S. Neyra, Silvia Medrano, Alexandre De Goes Martini, Maria Luisa S. Sequeira-Lopez, R. Ariel Gomez
Summary: The transcription factor Gata3 plays a crucial role in the identity and localization of renin cells in the kidney. Deletion of Gata3 leads to abnormal kidney development and misplacement of renin cells.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2023)
Review
Immunology
Zivile Bekassy, Ingrid Lopatko Fagerstrom, Michael Bader, Diana Karpman
Summary: This review explores the complex interactions between the renin-angiotensin system, complement system, and kallikrein-kinin system, as well as their dysregulation in different conditions and therapeutic implications. Various mediators modulate the balance between vascular tone, inflammation, coagulation, and thrombosis during severe inflammatory and infectious diseases. These systems play important roles in cell biological functions, such as regulating vascular tone, inflammation, and thrombosis.
NATURE REVIEWS IMMUNOLOGY
(2022)