Heart-type fatty acid binding protein

Heart-type fatty acid binding protein (hFABP) also known as mammary-derived growth inhibitor is a protein that in humans is encoded by the FABP3 gene.[5][6]

FABP3
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesFABP3, FABP11, H-FABP, M-FABP, MDGI, O-FABP, Heart-type fatty acid binding protein, fatty acid binding protein 3
External IDsOMIM: 134651 MGI: 95476 HomoloGene: 68379 GeneCards: FABP3
Orthologs
SpeciesHumanMouse
Entrez

2170

14077

Ensembl

ENSG00000121769

ENSMUSG00000028773

UniProt

P05413

P11404

RefSeq (mRNA)

NM_004102
NM_001320996

NM_010174

RefSeq (protein)

NP_001307925
NP_004093

NP_034304

Location (UCSC)Chr 1: 31.37 – 31.38 MbChr 4: 130.2 – 130.21 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

Heart-type Fatty Acid-Binding Protein (H-FABP) is a small cytoplasmic protein (15 kDa) released from cardiac myocytes following an ischemic episode.[7] Like the nine other distinct FABPs that have been identified, H-FABP is involved in active fatty acid metabolism where it transports fatty acids from the cell membrane to mitochondria for oxidation.[7] See FABP3 for biochemical details.

The intracellular fatty acid-binding proteins (FABPs) belongs to a multigene family. FABPs are divided into at least three distinct types, namely the hepatic-, intestinal- and cardiac-type. They form 14-15 kDa proteins and are thought to participate in the uptake, intracellular metabolism and/or transport of long-chain fatty acids. They may also be responsible in the modulation of cell growth and proliferation. Fatty acid-binding protein 3 gene contains four exons and its function is to arrest growth of mammary epithelial cells. This gene is also a candidate tumor suppressor gene for human breast cancer.[6]

Interactions

FABP3 is known to interact with TNNI3K in the context of interacting with cardiac troponin I.[8] The protein also interacts with, VPS28, KIAA159,[9] NUP62,[10] PLK1, UBC, and Xpo1.[6]

In HIV, a synthetic peptide corresponding to the immunosuppressive domain (amino acids 574-592) of HIV-1 gp41 downregulates the expression of fatty acid binding protein 3 (FABP3) in peptide-treated PBMCs.[11]

Clinical significance

Diagnostic potential

H-FABP is a sensitive biomarker for myocardial infarction[12][13] and can be detected in the blood within one to three hours of the pain.

The diagnostic potential of the biomarker H-FABP for heart injury was discovered in 1988 by Professor Jan Glatz (Maastricht, Netherlands).[14] H-FABP is 20 times more specific to cardiac muscle than myoglobin,[14] it is found at 10-fold lower levels in skeletal muscle than heart muscle and the amounts in the kidney, liver and small intestine are even lower again.[15][16]

H-FABP is recommended to be measured with troponin to identify myocardial infarction and acute coronary syndrome in patients presenting with chest pain. H-FABP measured with troponin shows increased sensitivity of 20.6% over troponin at 3–6 hours following chest pain onset.[17] This sensitivity may be explained by the high concentration of H-FABP in myocardium compared to other tissues, the stability and solubility of H-FABP, its low molecular weight; 15kDa compared to 18, 80 and 37kDa for MYO, CK-MB and cTnT respectively,[18][19][20] its rapid release into plasma after myocardial injury – 60 minutes after an ischemic episode,[21] and its relative tissue specificity.[22] Similarly this study showed that measuring H-FABP in combination with troponin increased the diagnostic accuracy and with a negative predictive value of 98% could be used to identify those not suffering from MI at the early time point of 3–6 hours post chest pain onset.[17] The effectiveness of using the combination of H-FABP with troponin to diagnose MI within 6 hours is well reported.[23][24][25]

Prognostic potential

In addition to its diagnostic potential, H-FABP also has prognostic value. Alongside D-dimer, NT-proBNP and peak troponin T, it was the only cardiac biomarker that proved to be a statistically significant predictor of death or MI at one year. This prognostic information was independent of troponin T, ECG and clinical examination.[24] The risk associated with raised H-FABP is dependent upon its concentration.[26][27] Patients who were TnI negative but H-FABP positive had 17% increased risk of all cause mortality within one year compared to those patients who were TnI positive but H-FABP negative.[26] Currently these TnI positive patients are prioritised for angioplasty, and the TnI negative patients are considered to be of a lower priority, yet the addition of the H-FABP test helps identify patients who are currently slipping through the net and allows physicians to more appropriately manage this hidden high risk group. If both biomarkers were negative, there is 0% mortality at 6 months, in the authors own words this “represents a particularly worthwhile clinical outcome, especially because it was observed in patients admitted into hospital for suspected ACS.” H-FABP indicates risk across the ACS spectrum including UA, NSTEMI or STEMI where low H-FABP concentrations confer low risk whereas high H-FABP concentrations indicate patients who are at a much higher risk of future events.[26]

H-FABP in other diseases

H-FABP has been proven to significantly predict 30-day mortality in acute pulmonary embolism.[28] H-FABP is more effective than Troponin T in risk stratifying Chronic Heart Failure patients.[29] H-FABP is beginning to create interest with researchers who have found emerging evidence that indicates a role in differentiating between different neurodegenerative diseases.[30][31]

H-FABP Point of care testing

To obtain diagnostic and prognostic information a precise and fully quantitative measurement of H-FABP is required. Commercial tests include a Cardiac Array on Evidence MultiStat; and an automated biochemistry assay

See also

  • Akash Manoj – Indian inventor who developed wearable device to detect h-FABP

References

  1. GRCh38: Ensembl release 89: ENSG00000121769 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000028773 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Phelan CM, Larsson C, Baird S, Futreal PA, Ruttledge MH, Morgan K, Tonin P, Hung H, Korneluk RG, Pollak MN, Narod SA (May 1996). "The human mammary-derived growth inhibitor (MDGI) gene: genomic structure and mutation analysis in human breast tumors". Genomics. 34 (1): 63–8. doi:10.1006/geno.1996.0241. PMID 8661024. S2CID 22867711.
  6. "Entrez Gene: FABP3 fatty acid binding protein 3, muscle and heart (mammary-derived growth inhibitor)".
  7. Kleine AH, Glatz JF, Van Nieuwenhoven FA, Van der Vusse GJ (Oct 1992). "Release of heart fatty acid-binding protein into plasma after acute myocardial infarction in man". Molecular and Cellular Biochemistry. 116 (1–2): 155–62. doi:10.1007/BF01270583. PMID 1480144. S2CID 12883346.
  8. Zhao Y, Meng XM, Wei YJ, Zhao XW, Liu DQ, Cao HQ, Liew CC, Ding JF (May 2003). "Cloning and characterization of a novel cardiac-specific kinase that interacts specifically with cardiac troponin I". Journal of Molecular Medicine. 81 (5): 297–304. doi:10.1007/s00109-003-0427-x. PMID 12721663. S2CID 13468188.
  9. Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toksöz E, Droege A, Krobitsch S, Korn B, Birchmeier W, Lehrach H, Wanker EE (Sep 2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell. 122 (6): 957–68. doi:10.1016/j.cell.2005.08.029. hdl:11858/00-001M-0000-0010-8592-0. PMID 16169070. S2CID 8235923.
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  13. Watanabe K, Wakabayashi H, Veerkamp JH, Ono T, Suzuki T (May 1993). "Immunohistochemical distribution of heart-type fatty acid-binding protein immunoreactivity in normal human tissues and in acute myocardial infarct". The Journal of Pathology. 170 (1): 59–65. doi:10.1002/path.1711700110. PMID 8326460. S2CID 20506087.
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  19. Wodzig KW, Kragten JA, Hermens WT, Glatz JF, van Dieijen-Visser MP (Mar 1997). "Estimation of myocardial infarct size from plasma myoglobin or fatty acid-binding protein. Influence of renal function". European Journal of Clinical Chemistry and Clinical Biochemistry. 35 (3): 191–8. CiteSeerX 10.1.1.634.2919. doi:10.1515/cclm.1997.35.3.191. PMID 9127740. S2CID 33514349.
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Further reading

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