Heart-type fatty acid binding protein (hFABP) also known as mammary-derived growth inhibitor is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that in humans is encoded by the ''FABP3''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
Function
Heart-type Fatty Acid-Binding Protein (H-FABP) is a small cytoplasmic protein (15 kDa) released from cardiac
myocyte
A muscle cell is also known as a myocyte when referring to either a cardiac muscle cell (cardiomyocyte), or a smooth muscle cell as these are both small cells. A skeletal muscle cell is long and threadlike with many nuclei and is called a muscl ...
s following an
ischemic
Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems wi ...
episode.
Like the nine other distinct FABPs that have been identified, H-FABP is involved in active
fatty acid
In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, fr ...
metabolism where it transports fatty acids from the cell membrane to
mitochondria
A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
for oxidation.
See
FABP3
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.
Function
Heart-type Fatty Acid-Binding Protein (H-FABP) is a small cytoplasmic protein ( ...
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 acid
In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, fr ...
s. 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 cell
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...
s. This gene is also a candidate tumor suppressor gene for human
breast cancer
Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a re ...
.
Interactions
FABP3 is known to interact with
TNNI3K in the context of interacting with cardiac troponin I. The protein also interacts with,
VPS28
Vacuolar protein sorting-associated protein 28 homolog is a protein that in humans is encoded by the VPS28 gene.
Function
This gene encodes a protein involved in endosomal sorting of cell surface receptors via a multivesicular body/late endos ...
,
KIAA159,
NUP62
Nuclear pore glycoprotein p62
is a protein complex associated with the nuclear envelope. The p62 protein remains associated with the nuclear pore complex-lamina fraction. p62 is synthesized as a soluble cytoplasmic precursor of 61 kDa followed by ...
,
PLK1
Serine/threonine-protein kinase PLK1, also known as polo-like kinase 1 (PLK-1) or serine/threonine-protein kinase 13 (STPK13), is an enzyme that in humans is encoded by the ''PLK1'' (polo-like kinase 1) gene.
Structure
PLK1 consists of 603 ami ...
,
UBC
The University of British Columbia (UBC) is a public research university with campuses near Vancouver and in Kelowna, British Columbia. Established in 1908, it is British Columbia's oldest university. The university ranks among the top three ...
, and
Xpo1
Exportin 1 (XPO1), also known as chromosomal region maintenance 1 (CRM1), is a eukaryotic protein that mediates the nuclear export of various proteins and RNAs.
History
XPO1 (CRM1) originally was identified in the fission yeast ''Schizosaccharom ...
.
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.
Clinical significance
Diagnostic potential
H-FABP is a sensitive
biomarker
In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, ...
for
myocardial infarction
A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may ...
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).
H-FABP is 20 times more specific to cardiac muscle than
myoglobin
Myoglobin (symbol Mb or MB) is an iron- and oxygen-binding protein found in the cardiac and skeletal muscle tissue of vertebrates in general and in almost all mammals. Myoglobin is distantly related to hemoglobin. Compared to hemoglobin, myoglobi ...
,
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.
H-FABP is recommended to be measured with
troponin
image:Troponin Ribbon Diagram.png, 400px, Ribbon representation of the human cardiac troponin core complex (52 kDa core) in the calcium-saturated form. Blue = troponin C; green = troponin I; magenta = troponin T.; ; rendered with PyMOL
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.
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
The CPK-MB test (creatine phosphokinase-MB), also known as CK-MB test, is a cardiac marker used to assist diagnoses of an acute myocardial infarction, myocardial ischemia, or myocarditis. It measures the blood level of CK-MB (creatine kinase myoca ...
and
cTnT respectively,
its rapid release into plasma after myocardial injury – 60 minutes after an ischemic episode,
and its relative tissue specificity.
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.
The effectiveness of using the combination of H-FABP with troponin to diagnose MI within 6 hours is well reported.
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.
The risk associated with raised H-FABP is dependent upon its concentration.
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.
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.
H-FABP in other diseases
H-FABP has been proven to significantly predict 30-day mortality in acute
pulmonary embolism
Pulmonary embolism (PE) is a blockage of an pulmonary artery, artery in the lungs by a substance that has moved from elsewhere in the body through the bloodstream (embolism). Symptoms of a PE may include dyspnea, shortness of breath, chest pain p ...
.
H-FABP is more effective than Troponin T in risk stratifying Chronic Heart Failure patients.
H-FABP is beginning to create interest with researchers who have found emerging evidence that indicates a role in differentiating between different neurodegenerative diseases.
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
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Akash Manoj – Indian inventor who developed wearable device to detect h-FABP
References
Further reading
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{{Carrier proteins
Cardiology