Heart-type fatty acid binding protein
Encyclopedia
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
.
s following an ischemic
episode. 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. 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 cell
s. This gene is also a candidate tumor suppressor gene for human breast cancer
.
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
, 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
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 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.
. 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.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the FABP3 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Function
Heart-type Fatty Acid-Binding Protein (H-FABP) is a small cytoplasmic protein (15 kDa) released from cardiac myocyteMyocyte
A myocyte is the type of cell found in muscles. They arise from myoblasts.Each myocyte contains myofibrils, which are long, long chains of sarcomeres, the contractile units of the cell....
s following an ischemic
Ischemia
In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...
episode. Like the nine other distinct FABPs that have been identified, H-FABP is involved in active fatty acid
Fatty acid
In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...
metabolism where it transports fatty acids from the cell membrane to mitochondria for oxidation. See FABP3 for biochemical details.
The intracellular fatty acid-binding proteins (FABPs
Fatty acid-binding protein
The fatty-acid-binding proteins are a family of carrier proteins for fatty acids and other lipophilic substances such as eicosanoids and retinoids. These proteins are thought to facilitate the transfer of fatty acids between extra- and intracellular membranes...
) 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 cell
Epithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...
s. This gene is also a candidate tumor suppressor gene for human breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
.
Diagnostic potential
H-FABP is a sensitive biomarker for myocardial infarctionMyocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
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
Myoglobin is an iron- and oxygen-binding protein found in the muscle tissue of vertebrates in general and in almost all mammals. It is related to hemoglobin, which is the iron- and oxygen-binding protein in blood, specifically in the red blood cells. The only time myoglobin is found in the...
, 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
Troponin
400px|thumb|right|alt = Colored dice with checkered background|Ribbon representation of the human cardiac troponin core complex in the calcium-saturated form...
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
Myosin
Myosins comprise a family of ATP-dependent motor proteins and are best known for their role in muscle contraction and their involvement in a wide range of other eukaryotic motility processes. They are responsible for actin-based motility. The term was originally used to describe a group of similar...
, CK-MB and cTnT
Troponin complex
Troponin complex is a heteromeric protein playing an important role in the regulation of skeletal and cardiac muscle contraction. Troponin complex consists of three different subunits – troponin T , troponin I and troponin C . Each subunit is responsible for a part of troponin complex function...
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 embolismPulmonary embolism
Pulmonary embolism is a blockage of the main artery of the lung or one of its branches by a substance that has travelled from elsewhere in the body through the bloodstream . Usually this is due to embolism of a thrombus from the deep veins in the legs, a process termed venous thromboembolism...
. 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.