Utility of Serum Fatty Acid Concentrations as a Marker for Acute Myocardial Infarction and Their Potential Role in the Formation of Ischemia-Modified Albumin: A Pilot Study

Bhagavan, N.V.; Ha, Ji-Sook; Park, Joo-Ho; Honda, Stacey; Rios, Carlos N.; Sugiyama, Cheryl E.; Fujitani, Gale; Takeuchi, Irene K.; Ha, Chung-Eun

doi:10.1373/clinchem.2008.123315

Cited by 32 publications

(29 citation statements)

References 5 publications

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“…Myristate binding to BSA was shown to inhibit metal binding to both sites A (MBS) and B [37,149] (with the latter being the primary Co 2+ binding site [38]), resulting in a decrease in total Co 2+ -binding site availability and a corresponding increase in Co-DTT complex formation in the ACB assay [149] (Figures 2e and 2f). The results of this work, taken together with the already established link between elevated plasma FFA levels and MI [60,144,150,151], strongly suggest that IMA corresponds to albumin with increased levels of bound FFAs and not Nterminally modified albumin. These observations have important implications for the detection of MI as they suggest that "IMA" is strictly speaking neither a marker for ischemia nor oxidative stress, but a proxy measurement of plasma FFA levels.…”

Section: Ffa-loading Of Albumin As the Molecular Basis Of Ischemia-mosupporting

confidence: 67%

“…Under normal conditions, between 0.1 and 2 FFA molecules are carried per albumin molecule [19,57], but there a number of conditions, including fasting, extreme exercise [58], obesity, metabolic syndrome, diabetes mellitus, and cardiovascular disease [59] including atherosclerosis and myocardial infarction [60], under which up to four [19], or even more [61], FFA molecules can become bound. Importantly, many of these conditions are also associated with considerable shifts in plasma zinc levels, and these observations, together with our structural and thermodynamic studies, have led us to hypothesise that these correlations are mediated by HSA [15] -the main transporter for both zinc and FFAs in plasma.…”

Section: +mentioning

confidence: 99%

“…Soon after, based on the observation that plasma concentrations of FFAs rise during MI [150,151], a relationship between FFAs and the reversible generation of IMA was suggested [144], and Bhagavan et al found a "plausible but not causative relationship" between IMA levels and FFA levels in the sera of patients with acute myocardial infarction relative to controls, whereby an increase in FFA levels resulted in a lower Co 2+ -binding capacity, and hence an increase in IMA [60]. This explains why positive ACB tests are also found in a plethora disorders unrelated to MI, but which are associated with increased plasma concentrations of FFAs [141,142,144,145].…”

Section: Ffa-loading Of Albumin As the Molecular Basis Of Ischemia-momentioning

confidence: 99%

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Fatty Acid-Mediated Inhibition of Metal Binding to the Multi-Metal Site on Serum Albumin: Implications for Cardiovascular Disease

Blindauer

Khazaipoul²,

Yu³

et al. 2016

CTMC

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(2016) Fatty acid-mediated inhibition of metal binding to the multi-metal site on serum albumin : implications for cardiovascular disease. Current Trends in Medicinal Chemistry, 16. Permanent WRAP URL:http://wrap.warwick.ac.uk/78963 Copyright and reuse:The Warwick Research Archive Portal (WRAP) makes this work by researchers of the University of Warwick available open access under the following conditions. Copyright © and all moral rights to the version of the paper presented here belong to the individual author(s) and/or other copyright owners. To the extent reasonable and practicable the material made available in WRAP has been checked for eligibility before being made available.Copies of full items can be used for personal research or study, educational, or not-for-profit purposes without prior permission or charge. Provided that the authors, title and full bibliographic details are credited, a hyperlink and/or URL is given for the original metadata page and the content is not changed in any way.Publisher's statement: © Bentham Science Publishers. http://dx.doi.org/10.2174/1568026616666160216155927 A note on versions:The version presented here may differ from the published version or, version of record, if you wish to cite this item you are advised to consult the publisher's version. Please see the 'permanent WRAP URL' above for details on accessing the published version and note that access may require a subscription. Abstract: Human serum albumin (HSA) is the major protein in blood plasma and is responsible for circulatory transport of a range of small molecules including fatty acids, metal ions and drugs. We previously identified the major plasma Zn 2+ transport site on HSA and revealed that fatty-acid binding (at a distinct site called the FA2 site) and Zn 2+ binding are interdependent via an allosteric mechanism. Since binding affinities of long-chain fatty acids exceed those of plasma Zn 2+ , this means that under certain circumstances the binding of fatty acid molecules to HSA is likely to diminish HSA Zn 2+ -binding, and hence affects the control of circulatory and cellular Zn 2+ dynamics. This relationship between circulatory fatty acid and Zn 2+ dynamics is likely to have important physiological and pathological implications, especially since it has been recognised that Zn 2+ acts as a signalling agent in many cell types. Fatty acid levels in the blood are dynamic, but most importantly, chronic elevation of plasma fatty acid levels is associated with some metabolic disorders and disease states -including myocardial infarction and other cardiovascular diseases. In this article, we briefly review the metalbinding properties of albumin and highlight the importance of their interplay with fatty acid binding. We also consider the impact of this dynamic link upon levels and speciation of plasma Zn 2+ , its effect upon cellular Zn 2+ homeostasis and its relevance to cardiovascular and circulatory processes in health and disease.

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Section: Ffa-loading Of Albumin As the Molecular Basis Of Ischemia-mosupporting

confidence: 67%

Section: +mentioning

confidence: 99%

Section: Ffa-loading Of Albumin As the Molecular Basis Of Ischemia-momentioning

confidence: 99%

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Fatty Acid-Mediated Inhibition of Metal Binding to the Multi-Metal Site on Serum Albumin: Implications for Cardiovascular Disease

Blindauer

Khazaipoul²,

Yu³

et al. 2016

CTMC

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“…In addition, high concentrations of serum lipids are able to increase the instability of vulnerable plaques, aggravating artery stenosis or promoting the formation of blood clots, thereby aggravating ischemia and resulting in increased IMA (22). A second possibility is that highly concentrated serum combines with albumin to reduce binding sites of albumin and cobalt ions, causing a decrease in the binding capacity of albumin cobalt, which is manifested as increased levels of serum IMA (23).…”

Section: Discussionmentioning

confidence: 99%

Correlation between ischemia-modified albumin and lipid levels in patients with acute cerebrovascular disease

et al. 2012

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Abstract. Acute cerebrovascular disease (ACVD) is associated with high morbidity and mortality rates, however, molecular markers to aid in its early detection are lacking. In this study, we examined the correlation between serum ischemia-modified albumin (IMA), a marker used to identify ischemic events in the heart, and blood lipids in patients with ACVD. Serum IMA levels were determined by enzyme-linked immuno sorbent assay, and total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein cholesterol (HDL) and triglyceride (TG) levels were determined biochemically in 62 patients with cerebral infarction (CI), 40 patients with intracerebral hemorrhage (ICH), 18 patients with subarachnoid hemorrhage (SAH) and 100 healthy individuals (controls). Serum IMA levels were significantly higher in each of the ACVD groups compared to the control group (CI, 80.81±11.97 U/ml; ICH, 80.25±10.91 U/ml; SAH, 74.43±11.39 U/ml and control, 41.08±5.10 U/ml; P<0.05). Additionally, serum TC, LDL and TG levels significantly increased, while serum HDL significantly decreased in the ACVD groups compared to the control group (P<0.05). A positive correlation was found between serum IMA levels and serum TC, LDL and TG levels in the ACVD patients, while serum IMA levels were negatively correlated with serum HDL levels (P<0.05). Thus, serum IMA increased following an ACVD event and was closely correlated with changes in the blood lipid levels. These factors, when combined, may allow the development of molecular markers for an earlier diagnosis of ACVD.

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“…Some studies have indicated that IMA levels are increased in obesity-related abnormalities, such as hypercholesterolemia (7), type 2 diabetes (8,9), metabolic syndrome (10) and elevated free fatty acid (FFA) levels in the body (11). IMA is also increased in other conditions that are identified with free radical production, such as liver cirrhosis, acute infections and advanced cancer [12].…”

Section: Introductionmentioning

confidence: 99%

Association of ischemia-modified albumin with oxidative stress status and insulin resistance in obese patients

Yiğitbaşı

Baskın

Akgöl³

et al. 2017

Revista Romana De Medicina De Laborator

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Utility of Serum Fatty Acid Concentrations as a Marker for Acute Myocardial Infarction and Their Potential Role in the Formation of Ischemia-Modified Albumin: A Pilot Study

Cited by 32 publications

References 5 publications

Fatty Acid-Mediated Inhibition of Metal Binding to the Multi-Metal Site on Serum Albumin: Implications for Cardiovascular Disease

Fatty Acid-Mediated Inhibition of Metal Binding to the Multi-Metal Site on Serum Albumin: Implications for Cardiovascular Disease

Correlation between ischemia-modified albumin and lipid levels in patients with acute cerebrovascular disease

Association of ischemia-modified albumin with oxidative stress status and insulin resistance in obese patients

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