Article
Cardiac & Cardiovascular Systems
Tlili Barhoumi, Fatmah A. Mansour, Maroua Jalouli, Hassan S. Alamri, Rizwan Ali, Abdel Halim Harrath, Maha Aljumaa, Mohamed Boudjelal
Summary: Angiotensin II (Ang II) is a key component of the renin-angiotensin-aldosterone system and is associated with cardiopathology. High levels of Ang II have been linked to inflammatory conditions such as coronary heart disease, obesity, and type 2 diabetes. This study evaluated the cellular effects of Ang II on THP-1-derived macrophages, showing that it stimulates differentiation markers and proinflammatory markers while decreasing an M2 marker. Ang II also induces calcium overload, increases reactive oxygen species, and arrests cells in the G1 phase, primarily through the angiotensin II type 1 receptor (AT1R).
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Review
Pharmacology & Pharmacy
Robert Eckenstaler, Jana Sandori, Michael Gekle, Ralf A. Benndorf
Summary: The AT(1) receptor plays a significant role in cardiovascular and renal diseases, and is a major target for angiotensin receptor blockers such as sartans. Recent studies have provided new insights into the structure and biased signaling of this receptor, which could lead to the development of novel therapeutic approaches.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Urology & Nephrology
Daniel E. Leisman, Tiago D. Fernandes, Vanesa Bijol, Mabel N. Abraham, Jake R. Lehman, Matthew D. Taylor, Christine Capone, Omar Yaipan, Rinaldo Bellomo, Clifford S. Deutschman
Summary: The study found that sepsis reduces the expression of renal angiotensin II receptors, leading to changes in kidney blood flow and creatinine levels. Both mouse models and clinical observations suggest that angiotensin II prevents these functional changes, while AT1R blockade exacerbates them.
KIDNEY INTERNATIONAL
(2021)
Review
Biochemistry & Molecular Biology
Xi Zhang, Suli Zhang, Meili Wang, Hao Chen, Huirong Liu
Summary: Angiotensin II type 1 receptor (AT1R) is a promising therapeutic target for cardiovascular diseases. However, there have been no clinical trials on allosteric modulators of AT1R. This review summarizes the different allosteric modes of AT1R and discusses the future of drug design targeting AT1R allostery.
CELL AND BIOSCIENCE
(2023)
Article
Pharmacology & Pharmacy
Anastasios Lymperopoulos, Jordana Borges, Alexandra M. Carbone, Natalie Cora, Anastasiya Sizova
Summary: The angiotensin II type 1 receptor, essential in the cardiovascular system, has been extensively studied for its physiological and pathophysiological roles. Biased AT(1) receptor ligands have been developed to selectively activate beta-arrestin transduction pathways. However, the focus on G(q) or beta-arrestins tends to neglect other non-Gq-, non beta-arrestin-dependent signaling modalities employed by the versatile AT(1) receptor in cardiovascular tissues.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Endocrinology & Metabolism
Elizabeth K. M. Johnstone, Mohammed Akli Ayoub, Rebecca J. Hertzman, Heng B. See, Rekhati S. Abhayawardana, Ruth M. Seeber, Kevin D. G. Pfleger
Summary: This study investigated the heteromerization of AT(2) and B-2 receptors in HEK293FT cells. The results demonstrated the functional interaction between these receptors and the differences in signaling, providing important evidence for studying GPCR pharmacology and signaling diversity.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Aurelie Philippe, Gunnar Kleinau, Jason Jannis Gruner, Sumin Wu, Daniel Postpieszala, David Speck, Harald Heidecke, Simon J. Dowell, Gabriela Riemekasten, Peter W. Hildebrand, Julian Kamhieh-Milz, Rusan Catar, Michal Szczepek, Duska Dragun, Patrick Scheerer
Summary: This study investigates the effects of AT(1)R-Abs on G-protein signaling and cell proliferation, as well as the involvement of extracellular receptor loops. The results show that AT(1)R-Abs activate G(q/11) signaling, leading to cell proliferation and inhibiting receptor internalization. Additionally, ligand-independent activation of G(i) signaling by AT(1)R has a negative effect on cell proliferation. The study also identifies the involvement of certain extracellular receptor loops in the interaction between AT(1)R and antibodies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Daniel Fernandes, Leticia Kramer Pacheco, Regina Sordi, Karin Scheschowitsch, Gustavo Campos Ramos, Jamil Assreuy
Summary: A study found that early and partial blockade of the AT 1 receptor with a low dose of losartan can counteract sepsis-induced refractoriness to vasoconstrictors, providing an opportunity to improve the outcome of this condition.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Kohei Karasaki, Hiroki Kokubo, Batmunkh Bumdelger, Nobuchika Kaji, Chiemi Sakai, Mari Ishida, Masao Yoshizumi
Summary: This study found that Angiotensin II type 1 receptor blockers (ARBs) can prevent the progression of abdominal aortic aneurysm (AAA) by upregulating angiotensin (1-7), suggesting that angiotensin (1-7) may play a key role in mediating the protective effect of ARBs.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Article
Medicine, General & Internal
Na-Na Sun, Yue Zhang, Wen-Hui Huang, Bo-Jun Zheng, Si-Yi Jin, Xu Li, Ying Meng
Summary: The study reveals the crucial role of exosomes in mediating communication between macrophages and lung fibroblasts, leading to pulmonary fibrosis. The presence of Ang II in exosomes from macrophages creates a positive feedback loop.
CHINESE MEDICAL JOURNAL
(2021)
Article
Physiology
Juliano Zequini Polidoro, Nancy Amaral Reboucas, Adriana Castello Costa Girardi
Summary: The study demonstrates that ATRAP attenuates Ang II-induced inhibition of ROMK in collecting duct cells by reducing c-Src activation and blocking ROMK internalization.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Immunology
Jelle R. Miedema, Matthijs L. Janssen, Jan von der Thuesen, Henrik Endeman, Anton W. Langerak, Merel E. Hellemons, Els van Nood, Bas W. A. Peeters, Sara J. Baart, Marco W. J. Schreurs
Summary: This study aimed to determine whether antibodies against AT1R and ETAR are specifically related to COVID-19 disease pathogenesis or increased during any severe respiratory illness. The results showed significantly increased AT1R and ETAR antibody titers in COVID-19 patients compared to controls, while these titers were not correlated with inflammatory markers or long-term symptoms.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Giovanni Civieri, Laura Iop, Francesco Tona
Summary: This review summarizes the current evidence regarding the effects of AT1R-AAs and ETAR-AAs in cardiovascular pathologies, highlighting their roles in heart transplantation and mechanical circulatory support, preeclampsia, and acute coronary syndromes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Krysten E. Ferraino, Natalie Cora, Celina M. Pollard, Anastasiya Sizova, Jennifer Maning, Anastasios Lymperopoulos
Summary: Angiotensin II (AngII) utilizes AT1R and AT2R G protein-coupled receptors to exert physiological effects, particularly impacting cardiovascular homeostasis. AT1R signaling mobilizes multiple signal transducers inside cells, with Gq/11 proteins and ?-arrestins specifically activated to promote aldosterone synthesis and secretion in the adrenal cortex. "Biased" signaling refers to preferential activation of one signaling pathway over others downstream of the same receptor, with therapeutic relevance in selectively promoting beneficial effects over detrimental consequences.
CELLULAR SIGNALLING
(2021)
Article
Medicine, Research & Experimental
Ziwei Fu, Fei Wang, Xiyang Liu, Jiajia Hu, Jiahui Su, Xiaohan Lu, Aihua Lu, Jae Min Cho, J. David Symons, Chang-Jiang Zou, Tianxin Yang
Summary: This study demonstrates that sPRR acts as a ligand of the AT1R, contributing to endothelial dysfunction and arterial dysfunction, as well as elevated blood pressure in obese mice. Inhibiting sPRR signaling through the AT1R may be a potential therapeutic intervention for cardiovascular disorders involving hypertension.