Elastin
Encyclopedia
Elastin is a protein
in connective tissue
that is elastic
and allows many tissues in the body to resume their shape after stretching or contracting. Elastin helps skin to return to its original position when it is poked or pinched. Elastin is also an important load-bearing tissue in the bodies of vertebrates and used in places where mechanical energy is required to be stored. In humans, elastin is encoded by the ELN gene
.
and proline
, which form mobile hydrophobic regions bounded by crosslinks between lysine
residues. Multiple transcript variants encoding different isoforms have been found for this gene. The other name for elastin is tropoelastin. The characterization of disorder is consistent with an entropy-driven mechanism of elastic recoil. It is concluded that conformational disorder is a constitutive feature of elastin structure and function.
) and autosomal dominant cutis laxa
. Other associated defects in elastin include Marfan's Syndrome and emphysema
caused by alpha-1-antitrypsin deficiency.
and elastin made of simple amino acid
s such as glycine
, valine
, alanine
, and proline
. The total elastin ranges from 58 to 75% of the weight of the dry defatted artery in normal canines arteries. Comparison between fresh and digested tissues shows that, at 35% strain, a minimum of 48% of the arterial load is carried by elastin, and a minimum of 43% of the change in stiffness of arterial tissue is due to the change in elastin stiffness.
Elastin is made by linking many soluble tropoelastin
protein molecules, in a reaction catalyzed
by lysyl oxidase
, to make a massive insoluble, durable cross-link
ed array. The amino acid responsible for these cross-links is lysine
. Tropoelastin is a specialized protein with a molecular weight of 64 to 66 kDa
, and an irregular or random coil conformation made up of 830 amino acids.
Desmosine
and isodesmosine
are types of links for the tropoelastin molecules.
and is particularly abundant in large elastic blood vessels such as the aorta
. Elastin is also very important in the lung
s, elastic ligaments
, the skin
, and the bladder
, elastic cartilage
. It is present in all vertebrates above the jawless fish.
Marketing Center and the Office of Public Affairs put a story by Morgan E. Kelly online (found at the university's home page) on Monday, January 31, 2011, stating that researchers have grown arteries (in a remarkably simple process that is easier than previous methods- using either virally-induced gene alteration, or transforming growth factor, or rolling cell sheets into tubes) that exhibit the elasticity of natural blood vessels at the highest levels reported. This is a development that could overcome a major barrier to creating living-tissue replacements for damaged arteries, according to the team's report in the Proceedings of the National Academy of Sciences
. The team, including postdoctoral researcher Kee-Won Lee and Pitt School of Medicine professor Donna Stolz, was led by lead author Yadong Wang, a professor of bioengineering in Pitt's Swanson School of Engineering
. They used smooth muscle cells from 4-year-old adult baboons (equivalent in age to 20-year-old humans) that were transferred to degradable honey comb-like rubber tube. The tubes were then transferred to a bioreactor for culturing, where a nutrient-rich solution was pumped through the tubes under conditions mimicking the human circulatory system- the pump produced a regular pulse, and the fluid was kept at 98.6 degrees Fahrenheit . As the muscle cells grew, they produced proteins that fused to form the vessel. Mechanical tests revealed that the cultured artery could withstand a burst pressure between 200 and 300 millimeters of mercury (mmHg). Healthy human blood pressure is between 120 and 80 mmHg. However, native arteries can withstand pressures ten times that of their constructs and contain up to 15 times more elastin. To quantify the elastin present in the engineered vessel, the researchers used two methods: a Fastin Elastin assay (Biocolor, UK), which quantifies elastin by binding the protein with a dye, and a desmosine ELISA
, which quantifies the amount of elastin cross-linking present and is indicative or mature elastin, unlike the Fastin Elastin assay. The desmosine ELISA
revealed that the engineered tissues produced 19% of the mature elastin present in native arteries positive controls (common carotid arteries from 3-year-old male baboons and 3.5-year-old femail wild type pigs. The arteries contained only 10% collagen, which is much lower than native arteries or even tissue engineered arteries made by other groups.
Thus elastin is a natural biomedical material of great potential. Being endowed with the special crosslinking and hydrophobic structure, elastin retains many good properties such as good elasticity, ductibility, biocompatibility, biodegradability and so on. Nowadays, elastin as a material, which is gradually attracting people' s attention in the biomedical materials field, has been used as tissue engineering scaffolds, derma substitutes and other biomedical materials.
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...
in connective tissue
Connective tissue
"Connective tissue" is a fibrous tissue. It is one of the four traditional classes of tissues . Connective Tissue is found throughout the body.In fact the whole framework of the skeleton and the different specialized connective tissues from the crown of the head to the toes determine the form of...
that is elastic
Elasticity (physics)
In physics, elasticity is the physical property of a material that returns to its original shape after the stress that made it deform or distort is removed. The relative amount of deformation is called the strain....
and allows many tissues in the body to resume their shape after stretching or contracting. Elastin helps skin to return to its original position when it is poked or pinched. Elastin is also an important load-bearing tissue in the bodies of vertebrates and used in places where mechanical energy is required to be stored. In humans, elastin is encoded by the ELN 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
This gene encodes a protein that is one of the two components of elastic fibers. The encoded protein is rich in hydrophobic amino acids such as glycineGlycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
and proline
Proline
Proline is an α-amino acid, one of the twenty DNA-encoded amino acids. Its codons are CCU, CCC, CCA, and CCG. It is not an essential amino acid, which means that the human body can synthesize it. It is unique among the 20 protein-forming amino acids in that the α-amino group is secondary...
, which form mobile hydrophobic regions bounded by crosslinks between lysine
Lysine
Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....
residues. Multiple transcript variants encoding different isoforms have been found for this gene. The other name for elastin is tropoelastin. The characterization of disorder is consistent with an entropy-driven mechanism of elastic recoil. It is concluded that conformational disorder is a constitutive feature of elastin structure and function.
Clinical significance
Deletions and mutations in this gene are associated with supravalvular aortic stenosis (SVASAortic valve stenosis
Aortic valve stenosis is a disease of the heart valves in which the opening of the aortic valve is narrowed. The aortic valve is the valve between the left ventricle of the heart and the aorta, which is the largest artery in the body and carries the entire output of blood.-Pathophysiology:The...
) and autosomal dominant cutis laxa
Cutis laxa
Cutis laxa is a group of rare connective tissue disorders in which the skin becomes inelastic and hangs loosely in folds.-Causes:In most cases, cutis laxa is inherited...
. Other associated defects in elastin include Marfan's Syndrome and emphysema
Emphysema
Emphysema is a long-term, progressive disease of the lungs that primarily causes shortness of breath. In people with emphysema, the tissues necessary to support the physical shape and function of the lungs are destroyed. It is included in a group of diseases called chronic obstructive pulmonary...
caused by alpha-1-antitrypsin deficiency.
Composition
Elastic fiber is composed of the protein fibrillinFibrillin
Fibrillin is a glycoprotein, which is essential for the formation of elastic fibers found in connective tissue.Fibrillin is secreted into the extracellular matrix by fibroblasts and becomes incorporated into the insoluble microfibrils, which appear to provide a scaffoldfor deposition of elastin.It...
and elastin made of simple amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s such as glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
, valine
Valine
Valine is an α-amino acid with the chemical formula HO2CCHCH2. L-Valine is one of 20 proteinogenic amino acids. Its codons are GUU, GUC, GUA, and GUG. This essential amino acid is classified as nonpolar...
, alanine
Alanine
Alanine is an α-amino acid with the chemical formula CH3CHCOOH. The L-isomer is one of the 20 amino acids encoded by the genetic code. Its codons are GCU, GCC, GCA, and GCG. It is classified as a nonpolar amino acid...
, and proline
Proline
Proline is an α-amino acid, one of the twenty DNA-encoded amino acids. Its codons are CCU, CCC, CCA, and CCG. It is not an essential amino acid, which means that the human body can synthesize it. It is unique among the 20 protein-forming amino acids in that the α-amino group is secondary...
. The total elastin ranges from 58 to 75% of the weight of the dry defatted artery in normal canines arteries. Comparison between fresh and digested tissues shows that, at 35% strain, a minimum of 48% of the arterial load is carried by elastin, and a minimum of 43% of the change in stiffness of arterial tissue is due to the change in elastin stiffness.
Elastin is made by linking many soluble tropoelastin
Tropoelastin
Tropoelastin is a water-soluble molecule with a molecular weight of approximately 72,000 daltons. Multiple tropoelastin molecules covalently bind together with crosslinks to form the protein elastin that is very prevalent in the body. There is only one gene for this molecule and so only one protein...
protein molecules, in a reaction catalyzed
Catalysis
Catalysis is the change in rate of a chemical reaction due to the participation of a substance called a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. A catalyst may participate in multiple chemical transformations....
by lysyl oxidase
Lysyl oxidase
Lysyl oxidase also known as protein-lysine 6-oxidase is a protein that, in humans, is encoded by the LOX gene. Its inhibition can cause lathyrism, but, at the same time, its upregulation by tumor cells may promote metastasis of the existing tumor, causing it to become malignant and cancerous.-...
, to make a massive insoluble, durable cross-link
Cross-link
Cross-links are bonds that link one polymer chain to another. They can be covalent bonds or ionic bonds. "Polymer chains" can refer to synthetic polymers or natural polymers . When the term "cross-linking" is used in the synthetic polymer science field, it usually refers to the use of...
ed array. The amino acid responsible for these cross-links is lysine
Lysine
Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....
. Tropoelastin is a specialized protein with a molecular weight of 64 to 66 kDa
Atomic mass unit
The unified atomic mass unit or dalton is a unit that is used for indicating mass on an atomic or molecular scale. It is defined as one twelfth of the rest mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state, and has a value of...
, and an irregular or random coil conformation made up of 830 amino acids.
Desmosine
Desmosine
A desmosine cross-link is formed from three allysyl side chains plus one unaltered lysyl side chain from the same or neighbouring polypeptides.It is found in elastin. Desmosine causes a yellow color....
and isodesmosine
Isodesmosine
Isodesmosine is a lysine derivative found in elastin....
are types of links for the tropoelastin molecules.
Tissue distribution
Elastin serves an important function in arteries as a medium for pressure wave propagation to help blood flowBlood flow
Blood flow is the continuous running of blood in the cardiovascular system.The human body is made up of several processes all carrying out various functions. We have the gastrointestinal system which aids the digestion and the absorption of food...
and is particularly abundant in large elastic blood vessels such as the aorta
Aorta
The aorta is the largest artery in the body, originating from the left ventricle of the heart and extending down to the abdomen, where it branches off into two smaller arteries...
. Elastin is also very important in the lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
s, elastic ligaments
Ligament
In anatomy, the term ligament is used to denote any of three types of structures. Most commonly, it refers to fibrous tissue that connects bones to other bones and is also known as articular ligament, articular larua, fibrous ligament, or true ligament.Ligament can also refer to:* Peritoneal...
, the skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
, and the bladder
Urinary bladder
The urinary bladder is the organ that collects urine excreted by the kidneys before disposal by urination. A hollow muscular, and distensible organ, the bladder sits on the pelvic floor...
, elastic cartilage
Elastic cartilage
Elastic cartilage or yellow cartilage is a type of cartilage present in the outer ear, larynx, and epiglottis. It contains elastic fiber networks and collagen fibers. The principal protein is elastin....
. It is present in all vertebrates above the jawless fish.
Use in biomedical engineering research
The University of PittsburghUniversity of Pittsburgh
The University of Pittsburgh, commonly referred to as Pitt, is a state-related research university located in Pittsburgh, Pennsylvania, United States. Founded as Pittsburgh Academy in 1787 on what was then the American frontier, Pitt is one of the oldest continuously chartered institutions of...
Marketing Center and the Office of Public Affairs put a story by Morgan E. Kelly online (found at the university's home page) on Monday, January 31, 2011, stating that researchers have grown arteries (in a remarkably simple process that is easier than previous methods- using either virally-induced gene alteration, or transforming growth factor, or rolling cell sheets into tubes) that exhibit the elasticity of natural blood vessels at the highest levels reported. This is a development that could overcome a major barrier to creating living-tissue replacements for damaged arteries, according to the team's report in the Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences
The Proceedings of the National Academy of Sciences of the United States of America, usually referred to as PNAS, is the official journal of the United States National Academy of Sciences...
. The team, including postdoctoral researcher Kee-Won Lee and Pitt School of Medicine professor Donna Stolz, was led by lead author Yadong Wang, a professor of bioengineering in Pitt's Swanson School of Engineering
Swanson School of Engineering
The Swanson School of Engineering is the engineering school of the University of Pittsburgh in Pittsburgh, Pennsylvania. Founded in 1846, The Swanson School of Engineering is the second or third oldest in the United States.- History :...
. They used smooth muscle cells from 4-year-old adult baboons (equivalent in age to 20-year-old humans) that were transferred to degradable honey comb-like rubber tube. The tubes were then transferred to a bioreactor for culturing, where a nutrient-rich solution was pumped through the tubes under conditions mimicking the human circulatory system- the pump produced a regular pulse, and the fluid was kept at 98.6 degrees Fahrenheit . As the muscle cells grew, they produced proteins that fused to form the vessel. Mechanical tests revealed that the cultured artery could withstand a burst pressure between 200 and 300 millimeters of mercury (mmHg). Healthy human blood pressure is between 120 and 80 mmHg. However, native arteries can withstand pressures ten times that of their constructs and contain up to 15 times more elastin. To quantify the elastin present in the engineered vessel, the researchers used two methods: a Fastin Elastin assay (Biocolor, UK), which quantifies elastin by binding the protein with a dye, and a desmosine ELISA
ELISA
Enzyme-linked immunosorbent assay , is a popular format of a "wet-lab" type analytic biochemistry assay that uses one sub-type of heterogeneous, solid-phase enzyme immunoassay to detect the presence of a substance in a liquid sample."Wet lab" analytic biochemistry assays involves detection of an...
, which quantifies the amount of elastin cross-linking present and is indicative or mature elastin, unlike the Fastin Elastin assay. The desmosine ELISA
ELISA
Enzyme-linked immunosorbent assay , is a popular format of a "wet-lab" type analytic biochemistry assay that uses one sub-type of heterogeneous, solid-phase enzyme immunoassay to detect the presence of a substance in a liquid sample."Wet lab" analytic biochemistry assays involves detection of an...
revealed that the engineered tissues produced 19% of the mature elastin present in native arteries positive controls (common carotid arteries from 3-year-old male baboons and 3.5-year-old femail wild type pigs. The arteries contained only 10% collagen, which is much lower than native arteries or even tissue engineered arteries made by other groups.
Thus elastin is a natural biomedical material of great potential. Being endowed with the special crosslinking and hydrophobic structure, elastin retains many good properties such as good elasticity, ductibility, biocompatibility, biodegradability and so on. Nowadays, elastin as a material, which is gradually attracting people' s attention in the biomedical materials field, has been used as tissue engineering scaffolds, derma substitutes and other biomedical materials.