Decoding Angiotensin Receptors: TOMAHAQ‐Based Detection and Quantification of Angiotensin Type‐1 and Type‐2 Receptors
Background The renin‐angiotensin system plays a crucial role in human physiology, and its main hormone, angiotensin, activates 2 G‐protein–coupled receptors, the angiotensin type‐1 and type‐2 receptors, in almost every organ. However, controversy exists about the location, distribution, and expressi...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-09-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.123.030791 |
| _version_ | 1827766247778942976 |
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| author | Caglar Cosarderelioglu Simion Kreimer Alma I. Plaza‐Rodriguez Pablo A. Iglesias C. Conover Talbot Helmy M. Siragy Robert M. Carey Ceereena Ubaida‐Mohien Brian O'Rourke Luigi Ferrucci David A. Bennett Jeremy Walston Peter Abadir |
| author_facet | Caglar Cosarderelioglu Simion Kreimer Alma I. Plaza‐Rodriguez Pablo A. Iglesias C. Conover Talbot Helmy M. Siragy Robert M. Carey Ceereena Ubaida‐Mohien Brian O'Rourke Luigi Ferrucci David A. Bennett Jeremy Walston Peter Abadir |
| author_sort | Caglar Cosarderelioglu |
| collection | DOAJ |
| description | Background The renin‐angiotensin system plays a crucial role in human physiology, and its main hormone, angiotensin, activates 2 G‐protein–coupled receptors, the angiotensin type‐1 and type‐2 receptors, in almost every organ. However, controversy exists about the location, distribution, and expression levels of these receptors. Concerns have been raised over the low sensitivity, low specificity, and large variability between lots of commercially available antibodies for angiotensin type‐1 and type‐2 receptors, which makes it difficult to reconciliate results of different studies. Here, we describe the first non–antibody‐based sensitive and specific targeted quantitative mass spectrometry assay for angiotensin receptors. Methods and Results Using a technique that allows targeted analysis of multiple peptides across multiple samples in a single mass spectrometry analysis, known as TOMAHAQ (triggered by offset, multiplexed, accurate mass, high resolution, and absolute quantification), we have identified and validated specific human tryptic peptides that permit identification and quantification of angiotensin type‐1 and type‐2 receptors in biological samples. Several peptide sequences are conserved in rodents, making these mass spectrometry assays amenable to both preclinical and clinical studies. We have used this method to quantify angiotensin type‐1 and type‐2 receptors in postmortem frontal cortex samples of older adults (n=28) with Alzheimer dementia. We correlated levels of angiotensin receptors to biomarkers classically linked to renin‐angiotensin system activation, including oxidative stress, inflammation, amyloid‐β load, and paired helical filament‐tau tangle burden. Conclusions These robust high‐throughput assays will not only catalyze novel mechanistic studies in the angiotensin research field but may also help to identify patients with an unbalanced angiotensin receptor distribution who would benefit from angiotensin receptor blocker treatment. |
| first_indexed | 2024-03-11T11:38:58Z |
| format | Article |
| id | doaj.art-c63cbfb65a3c494ba6fb143ad5cb0e65 |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-03-11T11:38:58Z |
| publishDate | 2023-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-c63cbfb65a3c494ba6fb143ad5cb0e652023-11-10T10:23:41ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802023-09-01121810.1161/JAHA.123.030791Decoding Angiotensin Receptors: TOMAHAQ‐Based Detection and Quantification of Angiotensin Type‐1 and Type‐2 ReceptorsCaglar Cosarderelioglu0Simion Kreimer1Alma I. Plaza‐Rodriguez2Pablo A. Iglesias3C. Conover Talbot4Helmy M. Siragy5Robert M. Carey6Ceereena Ubaida‐Mohien7Brian O'Rourke8Luigi Ferrucci9David A. Bennett10Jeremy Walston11Peter Abadir12Division of Geriatric Medicine and Gerontology Johns Hopkins University School of Medicine Baltimore MDThe Mass Spectrometry and Proteomics Facility Johns Hopkins University School of Medicine Baltimore MDKrieger School of Arts and Sciences Johns Hopkins University Baltimore MDDepartment of Electrical and Computer Engineering, Whiting School of Engineering Johns Hopkins University Baltimore MDInstitute for Basic Biomedical Sciences, Johns Hopkins University School of Medicine Baltimore MDDivision of Endocrinology and Metabolism, Department of Medicine University of Virginia Charlottesville VADivision of Endocrinology and Metabolism, Department of Medicine University of Virginia Charlottesville VANational Institute on Aging, National Institutes of Health Baltimore MDDivision of Cardiology, Department of Medicine Johns Hopkins University Baltimore MDNational Institute on Aging, National Institutes of Health Baltimore MDRush Alzheimer’s Disease Center Rush University Medical Center Chicago ILDivision of Geriatric Medicine and Gerontology Johns Hopkins University School of Medicine Baltimore MDDivision of Geriatric Medicine and Gerontology Johns Hopkins University School of Medicine Baltimore MDBackground The renin‐angiotensin system plays a crucial role in human physiology, and its main hormone, angiotensin, activates 2 G‐protein–coupled receptors, the angiotensin type‐1 and type‐2 receptors, in almost every organ. However, controversy exists about the location, distribution, and expression levels of these receptors. Concerns have been raised over the low sensitivity, low specificity, and large variability between lots of commercially available antibodies for angiotensin type‐1 and type‐2 receptors, which makes it difficult to reconciliate results of different studies. Here, we describe the first non–antibody‐based sensitive and specific targeted quantitative mass spectrometry assay for angiotensin receptors. Methods and Results Using a technique that allows targeted analysis of multiple peptides across multiple samples in a single mass spectrometry analysis, known as TOMAHAQ (triggered by offset, multiplexed, accurate mass, high resolution, and absolute quantification), we have identified and validated specific human tryptic peptides that permit identification and quantification of angiotensin type‐1 and type‐2 receptors in biological samples. Several peptide sequences are conserved in rodents, making these mass spectrometry assays amenable to both preclinical and clinical studies. We have used this method to quantify angiotensin type‐1 and type‐2 receptors in postmortem frontal cortex samples of older adults (n=28) with Alzheimer dementia. We correlated levels of angiotensin receptors to biomarkers classically linked to renin‐angiotensin system activation, including oxidative stress, inflammation, amyloid‐β load, and paired helical filament‐tau tangle burden. Conclusions These robust high‐throughput assays will not only catalyze novel mechanistic studies in the angiotensin research field but may also help to identify patients with an unbalanced angiotensin receptor distribution who would benefit from angiotensin receptor blocker treatment.https://www.ahajournals.org/doi/10.1161/JAHA.123.030791angiotensinangiotensin type‐1 receptorangiotensin type‐2 receptorbrainTOMAHAQ (triggered by offsetmultiplexed |
| spellingShingle | Caglar Cosarderelioglu Simion Kreimer Alma I. Plaza‐Rodriguez Pablo A. Iglesias C. Conover Talbot Helmy M. Siragy Robert M. Carey Ceereena Ubaida‐Mohien Brian O'Rourke Luigi Ferrucci David A. Bennett Jeremy Walston Peter Abadir Decoding Angiotensin Receptors: TOMAHAQ‐Based Detection and Quantification of Angiotensin Type‐1 and Type‐2 Receptors Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease angiotensin angiotensin type‐1 receptor angiotensin type‐2 receptor brain TOMAHAQ (triggered by offset multiplexed |
| title | Decoding Angiotensin Receptors: TOMAHAQ‐Based Detection and Quantification of Angiotensin Type‐1 and Type‐2 Receptors |
| title_full | Decoding Angiotensin Receptors: TOMAHAQ‐Based Detection and Quantification of Angiotensin Type‐1 and Type‐2 Receptors |
| title_fullStr | Decoding Angiotensin Receptors: TOMAHAQ‐Based Detection and Quantification of Angiotensin Type‐1 and Type‐2 Receptors |
| title_full_unstemmed | Decoding Angiotensin Receptors: TOMAHAQ‐Based Detection and Quantification of Angiotensin Type‐1 and Type‐2 Receptors |
| title_short | Decoding Angiotensin Receptors: TOMAHAQ‐Based Detection and Quantification of Angiotensin Type‐1 and Type‐2 Receptors |
| title_sort | decoding angiotensin receptors tomahaq based detection and quantification of angiotensin type 1 and type 2 receptors |
| topic | angiotensin angiotensin type‐1 receptor angiotensin type‐2 receptor brain TOMAHAQ (triggered by offset multiplexed |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.123.030791 |
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