elastic fiber

STRUCTURE - Core: cross-linked elastin (rich in glycine, proline, and alanine; hydrophobic, non-glycosylated). Secreted as tropoelastin. - Scaffold: fibrillin-1 microfibrils (glycoprotein) surround the elastin core and guide its deposition. Fibrillin also sequesters TGF-β. - Cross-linking: Lysyl oxidase (requires copper and vitamin B6/pyridoxal phosphate as a cofactor in some contexts, mainly copper) oxidatively deaminates lysine residues on tropoelastin. This forms allysine, which condenses into desmosine cross-links. These cross-links give elastin its stretch and recoil. - Unlike collagen, elastin lacks the triple helix and is not hydroxylated (no vitamin C dependence).

SYNTHESIS 1. Fibroblasts and smooth muscle cells (in vessels) synthesize tropoelastin. 2. Tropoelastin is secreted and assembled on fibrillin microfibrils. 3. Lysyl oxidase cross-links it into mature elastin. Synthesis is mostly during fetal and early life. Turnover in adults is minimal.

DEGRADATION - Elastase (from neutrophils) breaks down elastin. - α1-antitrypsin inhibits elastase.

LOCATIONS (high-yield) - Lungs (alveolar recoil) - Aorta and large elastic arteries (Windkessel effect, which maintains diastolic pressure) - Skin (dermis) - Ligamenta flava (spine) and nuchal ligament - Vocal cords - Elastic cartilage (ear, epiglottis)

HISTOLOGY - Not seen well with H&E. - Stained with Verhoeff-van Gieson (black), orcein (brown/dark), and aldehyde fuchsin. - Appear as wavy, branching, refractile fibers.

CLINICAL CORRELATIONS - Marfan syndrome: AD mutation in FBN1 (fibrillin-1). Features: tall stature with arachnodactyly, pectus deformities, ectopia lentis (upward/superotemporal), mitral valve prolapse, aortic root dilation and dissection, cystic medial degeneration. Excess TGF-β signaling contributes. - Emphysema: α1-antitrypsin deficiency causes unopposed neutrophil elastase, which destroys elastin in alveolar walls. Result is panacinar emphysema (lower lobes) and loss of recoil. Smoking increases protease activity and causes centriacinar emphysema (upper lobes). - Williams syndrome: 7q11.23 microdeletion including the elastin (ELN) gene. Features: supravalvular aortic stenosis, elfin facies, hypercalcemia, and a friendly personality with cognitive impairment. - Cutis laxa: defects in elastin or fibulin. Loose, inelastic, sagging skin. - Menkes disease: ATP7A mutation causes copper deficiency, which causes reduced lysyl oxidase function. Features: kinky/steely hair, neurodegeneration, and weakened connective tissue and vessels. - Pseudoxanthoma elasticum: ABCC6 mutation. Calcification and fragmentation of elastic fibers. Features: "plucked chicken" skin (flexural areas), angioid streaks in the retina, and GI bleeding. - Aging and sun damage: solar elastosis causes wrinkling and leathery skin due to abnormal elastic fiber accumulation. - Aortic aneurysm and dissection: elastic fiber fragmentation (cystic medial necrosis). - Ehlers-Danlos syndromes are predominantly collagen defects, not elastin. This is a common distractor.

BOARD PEARLS - Elastin = stretch and recoil. Collagen = tensile strength. - Fibrillin → Marfan. Elastin gene (ELN) → Williams and supravalvular aortic stenosis. - Copper → lysyl oxidase → elastin and collagen cross-linking. - Desmosine is the unique elastin cross-link. Its urinary or serum levels are used as a biomarker of elastin degradation.