What Is Collagen Vascular Disease?

Collagen diseases are collagen and collagen gene variant diseases. Collagen is the main component of a variety of connective tissues, which maintains the complete structure of tissues and organs. Aggregation and membrane permeability are closely related. Too much or too little collagen production, and defects in the collagen structure can lead to disease.

Collagen disorders

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Collagen diseases are collagen and collagen gene variability

Collagen and collagen gene disorders

All collagen molecules have a three-helix structure consisting of three alpha chains. The three alpha chains of some collagens are the same, and the three alpha chains of some collagens are completely different. At present, 19 types of alpha chains with more than 30 different genetic structures have been identified. Each alpha chain is composed of repeated 2Gly2X2Y2 sequences, and its molecular formula is (Gly2X2Y) n. Gly (Gly) accounts for 1/3 of the total amino acids, and its fixed position limits the triple helix structure. X and Y represent amino acids other than glycine, of which proline and hydroxyproline are the most.

Type I collagen gene variant disease

Type collagen gene variant disease

Type III collagen gene variant disease

Type III collagen and type I collagen are similarly distributed, but are not present in bone and tendon fibers. Vessel walls, skin, and intestinal walls are all tissues rich in type III collagen. Type III collagen mutations are mainly seen in patients with type IV EDS and aneurysms. Type IV EDS is the most severe type of this syndrome and can sometimes be accompanied by aortic and bowel wall rupture. There are currently 20 types of mutations that have been identified, including substitutions, deletions, and mRNA splicing defects at different single bases.

In general, the aforementioned type I collagen mutations are also type III collagen mutations in type IV EDS. In type IV EDS, aortic rupture is a typical consequence of type III collagen mutations.

Kontusaari et al. [4] first reported evidence of type III collagen mutations in family members of patients with aneurysms, and found that glycine at position 619 of type III collagen was replaced by arginine in the family members. Since then, Kuivaniemi et al. [5], Deak et al. [6], Majamaa et al. [7], and Liu et al. [8] have also found that type III collagen structures and type III are present in the families of patients with multiple aortic aneurysms, including cerebral aneurysms, respectively. Abnormal collagen synthesis. Although arteriosclerosis and hypertension can accelerate the occurrence of aortic aneurysms, studies have shown that the underlying cause of aortic aneurysms is type III collagen genetic defects. Some people believe that mutations in the COL3A1 gene can be used as a genetic susceptibility marker for aortic aneurysms.

In addition, it is worth emphasizing that in addition to type III collagen, the arterial wall also contains other important proteins, such as elastin, fibril filaments. Therefore, in addition to type III collagen gene mutations, aneurysms can also be caused by mutations in elastin and fibrillin genes.

Type IV collagen gene variant disease

Type IV collagen exists only in the basement membrane. It has been known 20 years ago that type IV collagen is composed of two 1 () and one 2 (). In recent years, it has been found that 3 () is also present in type IV collagen molecules. 4 (IV) and 5 (IV), which are trace components of the basement membrane. The 5 () chain is encoded by the col4a5 gene and is located on the X chromosome containing the location of Alport syndrome.

type collagen gene variant disease

-type collagen is the main component of anchor fibers. It is located in the basement membrane of the epidermis and the papillary layer of the dermis, and participates in the formation of appendages that hold the skin. The evidence for anchor fiber abnormalities was originally found to be abnormal or reduced in number of anchor fiber morphologies in some patients with skin dissociation.

Later, people discovered the dominant and recessive genetic linkage gene COL7A1 of skin loosening. Through the study of members of the family of skin loosening, it was proved that mutation of COL7A1 gene can cause skin loosening. The mutation form is homozygous single base Group substitution, the methionine code is replaced by the lysine code in a highly conserved region at the C-terminus of the 1 () chain [11]. However, recently Christina et al. [12, 13] have reported that members of the family of skin dissociation have the phenomenon that glycine in exon 91 and exon 73 of COL7A1 gene is replaced by arginine.

The use of transgenic mice to study the sequence of mutant collagen genes has led to a further understanding of whether certain human diseases are caused by mutations in collagen genes [14, 15], and the sequence of mutant collagen genes can be further observed. Transgenic mice expressing a partial defect of the COL9A1 gene can develop osteoarthropathy with mild osteoporosis. Therefore, mutated type collagen gene and mutated type collagen gene can cause osteoporosis and osteoarthropathy. Transgenic mice expressing truncated type X collagen genes can develop metaphyseal abnormalities in the spine, suggesting that the corresponding human disease appears to be due to the COL10A1 mutation.

Clinical manifestations of collagenous diseases

Collagen synthesis involves post-translational modifications, a process that requires at least eight specific enzymes. Defects have been found in three of these enzymes, which are Lysyl hydroxylase, procollagen N protease, and Lysyl oxidase. Most type IV EDS have abnormal Lysyl hydroxylase activity, clinical manifestations are soft skin, excessive elasticity, excessive joint extension, scoliosis, spinal process, poor scar formation, hypotonia, retinal detachment, and fragility of the eye. Natural rupture can occur. Wait.

Important functions of collagen diseases

Hydrolysine has 2 important functions

The hydroxylysine formed in the Lysyl hydroxylase reaction has two important functions: it is the point of attachment of carbohydrates; maintains the stability of collagen molecules. Therefore, a deficiency in Lysyl hydroxylase activity will cause connective tissue disease. Type ED EDS is due to abnormal cleavage of the N-terminal pro-peptide of procollagen, of which type A and B2 are due to mutations in COL1A2, which prevents cleavage of the pro-peptide. There was no abnormality of type I collagen in EDSC type, and the cleavage was due to the deficiency of type I procollagen N protease activity.

Collagen disease syndrome types

type EDS and Menkes syndrome

Type EDS and Menkes syndrome are X-linked recessive hereditary diseases. The main feature is the abnormal copper metabolism caused by the deficiency of Lysyl hydroxylase activity. Its clinical manifestations are bladder diverticulum, inguinal hernia, loose skin and hyperextension, and skeletal abnormalities with extraoccipital bone warts. At present, people have only identified the above 6 mutant collagen genes among more than 30 collagen genes, which indicates that research on collagen gene mutations has just begun, and there will be more collagen gene mutation diseases that people need to explore and understand .