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Decoding Angiotensin Receptors: TOMAHAQ-Based Detection and Quantification of Angiotensin Type-1 and Type-2 Receptors
Caglar Cosarderelioglu1,2, Simion Kreimer3, Alma I Plaza-Rodriguez4
1Division of Geriatric Medicine and Gerontology Johns Hopkins University School of Medicine Baltimore MD.
Journal of the American Heart Association
|September 8, 2023
Summary
We developed a new mass spectrometry assay to precisely measure angiotensin receptors, overcoming limitations of previous antibody-based methods. This technique aids research into Alzheimer's disease and potential treatments targeting the renin-angiotensin system.
Area of Science:
- Biochemistry
- Neuroscience
- Pharmacology
Background:
- The renin-angiotensin system (RAS) is vital in human physiology, with angiotensin hormones acting on angiotensin type-1 (AT1R) and type-2 (AT2R) receptors.
- Existing antibody-based assays for AT1R and AT2R suffer from low sensitivity, specificity, and lot variability, hindering reliable research.
- Accurate quantification of angiotensin receptors is crucial for understanding their role in various organs and diseases.
Purpose of the Study:
- To develop and validate a novel, antibody-free, targeted quantitative mass spectrometry assay for angiotensin receptors.
- To apply this assay to quantify AT1R and AT2R in human brain samples from Alzheimer's disease patients.
- To explore correlations between angiotensin receptor levels and Alzheimer's disease biomarkers.
Main Methods:
- Utilized TOMAHAQ (triggered by offset, multiplexed, accurate mass, high resolution, and absolute quantification) mass spectrometry for targeted peptide analysis.
- Identified and validated specific human tryptic peptides for the precise quantification of AT1R and AT2R.
- Applied the assay to postmortem frontal cortex samples from 28 older adults with Alzheimer's dementia.
Main Results:
- Successfully developed and validated a sensitive and specific mass spectrometry assay for angiotensin receptors.
- Quantified AT1R and AT2R levels in Alzheimer's disease brain samples.
- Observed correlations between angiotensin receptor levels and biomarkers of oxidative stress, inflammation, amyloid-β, and tau pathology.
Conclusions:
- The developed TOMAHAQ assay provides a robust, high-throughput method for quantifying angiotensin receptors.
- This assay facilitates new mechanistic studies in the RAS field and can aid in identifying patients for angiotensin receptor blocker therapy.
- The findings may help stratify patients for targeted treatment based on angiotensin receptor distribution.
Keywords:
TOMAHAQ (triggered by offsetaccurate massand absolute quantification)angiotensinangiotensin type‐1 receptorangiotensin type‐2 receptorbrainhigh resolutionmultiplexedMore Related Videos
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