Biochemical Insights and Clinical Applications of Ischemia-Modified Albumin in Ischemic Conditions
Abstract
:1. Introduction
2. Atherosclerotic Coronary Artery Disease (ACAD)
2.1. Global Prevalence
2.2. Local Prevalence
2.3. Pathophysiology of CAD
2.4. Diagnostic Tests of CAD
2.5. Use of Biomarkers in the Diagnosis of CAD
3. Ischemia Modified Albumin (IMA) as a Biomarker of Myocardial Ischemia
3.1. Human Serum Albumin
3.2. Formation of IMA
3.2.1. First Model/Hypothesis—Auto Degradation of NTS
3.2.2. The Second Model—N-Terminal Site Modification by Free Radicals
3.2.3. 3rd Hypothesis—Acetylation of the N-Terminus
3.2.4. Other Hypotheses—Inhibition of Cobalt Binding to HSA by Fatty Acids
4. Detection Methods of IMA
4.1. Albumin Cobalt Binding (ACB) Assay
4.1.1. Further Investigations on ACB Assay
4.1.2. Automation of ACB Assay
4.2. Cobalt Albumin Binding (CAB) Assay
The Cobalt (II) Principal Binding Site Is Not the N-Terminus?
4.3. Albumin Copper Binding (ACuB) Assay
4.4. Nickel-Albumin Binding Assay
4.5. Quantum Dot Coupled X-ray Fluorescence Spectroscopy (Q-XFR)
4.6. Immunological Methods
Enzyme-Linked Immunosorbent Assay (ELISA)
4.7. Liquid Crystal Biosensor for IMA
4.8. Surface Plasmon Resonance (SPR) Immunosensor for IMA
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Method | Principle | Advantages | Limitations |
---|---|---|---|
Albumin Cobalt Binding (ACB) Test [29,30,42,43,58,60,69] | This is the most widely used traditional method. It relies on the decreased binding capacity of cobalt to the N-terminus of albumin due to ischemic modifications. | Simple, cost-effective, and can be performed with standard laboratory equipment. | Results can vary due to factors like albumin concentration and the presence of other interfering substances. Sensitivity and specificity can be lower compared to newer methods. |
Cobalt Albumin Binding (CAB) assay [42] | An improved version of the ACB assay. | This assay reduces the impact of pH fluctuations on the binding of cobalt ions to albumin by optimizing pH conditions and using NaH2PO4 buffer at pH 7.4. The assay requires smaller volumes of specimens and reagents, making it more efficient and cost-effective. | Lack of standard Human Serum Albumin (HSA) as a control. Effect of pH on cobalt-DTT Binding: Although pH optimization has been addressed, cobalt binding to DTT decreases significantly with pH reduction. |
Albumin Copper Binding (ACuB) assay [63] | It relies on the decreased binding capacity of copper to the N-terminus of albumin due to ischemic modifications. | Cu2+ ions, which have a higher binding affinity for the N-terminus of HSA, enhance the assay’s sensitivity. Lucifer yellow is a copper-selective agent that doesn’t denature protein structures and releases metal ions from binding sites like DTT. Direct fluorescence measurements can be obtained. | Environmental factors such as pH changes and the presence of competing ions could still impact the binding efficiency. Fluorescence measurement requires specific equipment and dyes. |
Nickel-Albumin Binding assay [64,65] | It relies on the decreased binding capacity of nickel to the N-terminus of albumin due to ischemic modifications. | Using nickel ions, which have a higher affinity for binding to the N-terminus of HSA than cobalt, enhances detection sensitivity. | Using DTT as a colorizing agent can denature protein structures and release metal ions from binding sites, potentially affecting the accuracy and reliability of the assay results. Requires precise control of reaction conditions While Ni2+ ions have a relatively high binding affinity, they are not as strong as Cu2+, which may limit the assay’s sensitivity compared to the Albumin Copper Binding (ACuB) assay. |
Quantum Dot coupled X-ray Fluorescence Spectroscopy (Q-XFR) [66,67,68] | Primary X-ray irradiates the target element, and that interaction emits a characteristic secondary X-ray, which an X-ray fluorescence detector will detect. This characteristic secondary X-ray is unique to a particular aspect of interest. The XRF peak’s intensity is related to its number of elements. | Higher specificity (95.9%) compared to the ACB assay (82.9%) This method effectively removes interferences from excessively high or low albumin levels by calculating the difference between total HSA and intact HSA levels. Rapid and accurate detection | Specialized X-ray fluorescence spectroscopy equipment is required, and specialized training and expertise are needed to operate it. Complexity of sample preparation |
Enzyme-Linked Immunosorbent Assay (ELISA) [69,70,72,73,74,75,76] | Specific antibodies bind the target antigen and detect the presence and quantity of antigens binding. | Precise detection of IMA using antibodies, targeting the specific protein modification associated with ischemia. Provides quantitative measurement of IMA levels Adjusting IMA values based on serum albumin levels can minimize false positives and negatives, ensuring more accurate results. | ELISA results may vary based on the timing of sample collection The procedure involves multiple steps. Despite high specificity, there is always a risk of non-specific binding, which can affect the accuracy of the assay results. |
Liquid crystal biosensor [77,78,79] | Liquid crystals are phase transition metals that exist between liquid and crystal states. They have both liquid and crystal properties. They respond readily to external stimuli such as changes in surface properties (binding specific biomolecules onto the surface), temperature, pressure, and electromagnetic field. These stimuli will alter the orientation of the LC and change the color/brightness of the sensor. | High sensitivity and specificity The method is simple and provides quick results. Changes in the LC orientation result in optical signal changes observable through a polarizing microscope, allowing for immediate visual detection of IMA levels. LC biosensors can detect various biomolecules, including proteins, antibodies, and cells, making them versatile tools for different diagnostic applications. | Need for specialized equipment External stimuli sensitivity must be controlled |
Surface Plasmon Resonance (SPR) immunosensor for IMA [81] | SPR is an optical-electrical phenomenon that occurs when a photon of incoming light strikes a metal surface. A portion of the light energy interacts with the metal surface, and the electrons in the metal surface move due to excitation. Electron movements are known as plasmons, traveling parallel to the metal surface. The plasmon oscillation, in turn, generates an electric field from the metal surface. This allows for more precise measurements of molecule adsorption on the metal surface and subsequent interactions with specific ligands. | High sensitivity in detecting IMA, particularly when enhanced with colloidal gold nanoparticles Real-time, in situ monitoring of biomolecular interactions Label-free detection Low interference Versatility and biocompatibility Rapid and simple | SPR systems require sophisticated and expensive equipment, which may limit their availability in resource-constrained settings. Specialized training is required to operate the instruments. Over time, the metal surface can become fouled with non-specific proteins or other contaminants. |
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Senadeera, N.N.; Ranaweera, C.B.; Perera, I.C.; Kottahachchi, D.U. Biochemical Insights and Clinical Applications of Ischemia-Modified Albumin in Ischemic Conditions. J. Vasc. Dis. 2024, 3, 245-266. https://doi.org/10.3390/jvd3030020
Senadeera NN, Ranaweera CB, Perera IC, Kottahachchi DU. Biochemical Insights and Clinical Applications of Ischemia-Modified Albumin in Ischemic Conditions. Journal of Vascular Diseases. 2024; 3(3):245-266. https://doi.org/10.3390/jvd3030020
Chicago/Turabian StyleSenadeera, Nimesha N., Chathuranga B. Ranaweera, Inoka C. Perera, and Darshana U. Kottahachchi. 2024. "Biochemical Insights and Clinical Applications of Ischemia-Modified Albumin in Ischemic Conditions" Journal of Vascular Diseases 3, no. 3: 245-266. https://doi.org/10.3390/jvd3030020
APA StyleSenadeera, N. N., Ranaweera, C. B., Perera, I. C., & Kottahachchi, D. U. (2024). Biochemical Insights and Clinical Applications of Ischemia-Modified Albumin in Ischemic Conditions. Journal of Vascular Diseases, 3(3), 245-266. https://doi.org/10.3390/jvd3030020