Disease relevance of ELN

• The cDNA was inserted into lambda gt10 using EcoRI linkers, and recombinant phage containing elastin sequences were identified by hybridization with a 1.3 kb sheep elastin cDNA clone, pcSELI (Yoon, K. et al., Biochem. Biophys. Res. Comm. 118: 261-265, 1984) [1].
• Persistence of the fetal pattern of tropoelastin gene expression in severe neonatal bovine pulmonary hypertension [2].
• In contrast, intralobar pulmonary arteries from calves exposed to hypoxia, which prevented the normal postnatal decline in pulmonary artery pressure, maintained the fetal pattern and levels of tropoelastin mRNA expression at all time points [2].
• In addition, we identified an SMC population defined by its immunoreactivity to the muscle-specific cytoskeletal protein meta-vinculin that did not express TE mRNA either during fetal PA development or postnatally when PA hypertension was induced [3].
• A bovine tropoelastin cDNA encoding exons 15-36 that includes the elastin-receptor binding site was expressed in Escherichia coli as a fusion protein with Protein A from Staphylococcus aureus [4].

High impact information on ELN

• Since lactose also blocks elastic fiber formation by cultured chondroblasts, the galactoside-binding property of the elastin receptor is implicated in this process [5].
• However, it is not clear if this is due to recruitment of quiescent smooth muscle cells (SMC) into an elastin-producing phenotype or persistence of the fetal pattern of tropoelastin gene expression [2].
• We evaluated the distribution and relative concentration of tropoelastin mRNA in intralobar pulmonary arteries from late gestation fetuses and in animals exposed to hypobaric hypoxia (430 mmHg) from birth for 1, 3, 7, or 14 d, as well as in age-matched and adult room air-breathing controls [2].
• We conclude that pulmonary hypertension in the neonate perturbs the normal postpartum repression of tropoelastin expression resulting in a persistence of the fetal spacial and isoform patterns of tropoelastin gene expression [2].
• These findings demonstrated that tropoelastin expression shuts off in a spatially specific pattern, moving from the abluminal to the luminal side of the medial in the neonatal pulmonary artery when pressures and resistance are falling [2].

Chemical compound and disease context of ELN

• In order to determine the direct effects of hypoxia on tropoelastin production by pulmonary artery SMC, cultured neonatal bovine pulmonary artery SMC were exposed to 3%, 10%, and 21% O2 concentrations for 48, 72, and 120 h and soluble tropoelastin was measured by direct immunoassay [6].
• Bovine ligamentum nuchae (mostly elastin) was only partially fixed by glutaraldehyde or osmium tetroxide but was effectively stiffened by dehydration [7].

Biological context of ELN

• Binding to tropoelastin was divalent cation-independent and was completely blocked by reduction and alkylation of either protein [8].
• For both fibrillins, the greatest increase in expression occurred during the last half of fetal development when elastin production is highest [9].
• In developing bovine aorta, fibrillin mRNA levels again paralleled tropoelastin expression although, compared to ligament, elastin synthesis began at an earlier fetal age in this tissue [9].
• The alignment of amino acid sequences of porcine tropoelastin tryptic peptides with the sequence for bovine elastin a results in the ordering of these tryptic peptides [10].
• Nucleotide sequence analysis of cDNA clones for bovine elastin revealed the occurrence of three mRNAs for elastin in fetal calf nuchal ligament, encoding three forms of elastins (a, b, and c, of 747, 733, and 713 amino acid residues, respectively) [10].

Anatomical context of ELN

• The antibody did not react with microfibrils which were distant from the interface with elastin [11].
• In cases of vascular calcification, the decreased expression of TE, FBN1, and LO may be partially responsible for decreased vascular elasticity and also for the decreased formation of new elastic fibers [12].
• Deposition of tropoelastin into the extracellular matrix requires a competent elastic fiber scaffold but not live cells [13].
• Together, these results suggest that the matrix elaborated by the cell is sufficient for the initial deposition of tropoelastin in the extracellular space and that elastin assembly may be influenced by the composition of sulfated proteoglycans in the matrix [13].
• Lysyl oxidase (LO), an enzyme secreted by vascular smooth muscle cells (VSMC), initiates the covalent crosslinking of polypeptide chains within collagen and elastin [14].

Associations of ELN with chemical compounds

• In addition to identification of sequences homologous to those found in porcine tropoelastin, the analyses defined a 58 amino acid sequence that forms the carboxy-terminal region of tropoelastin, and this sequence, which contains two cysteine residues, was previously not observed in the protein sequence data [15].
• Association of exogenously added tropoelastin to the cellular extracellular matrix was inhibited by the addition of heparan sulfate but not chondroitin sulfate sugars [13].
• Lysyl oxidase initiates the covalent cross-linking of elastin and collagen by oxidizing lysine residues in these proteins to alpha-aminoadipic-delta-semialdehyde [16].
• A procedure has been developed which is much more specific for the solubilization of the elastin-associated microfibrils from fetal bovine nuchal ligament using treatment with reductive saline in place of reductive guanidine hydrochloride buffer [17].
• Lysyl oxidase initiates the covalent cross-linking of elastin and collagen, converting lysyl residues in these proteins to peptidyl aldehyde residues [18].

Physical interactions of ELN

• Microfibril-associated glycoprotein binds to the carboxyl-terminal domain of tropoelastin and is a substrate for transglutaminase [8].

Enzymatic interactions of ELN

• A significant characteristic of cathepsin S is that it can hydrolyze insoluble elastin at both acidic and neutral pH; this distinguishes it from all of the other lysosomal proteinases [19].

Regulatory relationships of ELN

• Insulin-like growth factor I stimulates elastin synthesis by bovine pulmonary arterial smooth muscle cells [20].

Other interactions of ELN

• Lysyl oxidase was similarly localized in newborn rat aorta at the interface between microfibrils and nascent elastin fibers [11].
• When tested in solid-phase binding assays, native MAGP specifically bound to tropoelastin but not fibrillin-1 [8].
• In fetal bovine nuchal ligament, mRNA levels for fibrillin-1 and fibrillin-2 increased approximately threefold during this period, whereas tropoelastin increased 20-fold [9].
• Complementary DNA cloning establishes microfibril-associated glycoprotein (MAGP) to be a discrete component of the elastin-associated microfibrils [21].
• Persistence, re-expression, and induction of pulmonary arterial fibronectin, tropoelastin, and type I procollagen mRNA expression in neonatal hypoxic pulmonary hypertension [22].

Analytical, diagnostic and therapeutic context of ELN

• Electron microscopy of calf aortic specimens revealed discrete gold deposits at the interface between extracellular bundles of amorphous elastin and the microfibrils circumferentially surrounding these bundles [11].
• As determined by Western blot analysis, 10 mM of beta-GP time-dependently decreased TE and FBN1 protein levels [12].
• A bovine genomic library constructed by partial Sau3A digestion and contained in lambda Charon 30 was screened by in situ hybridization with a 1.3-kilobase (kb) sheep elastin cDNA clone [Yoon, K., May, M., Goldstein, N., Indik, Z., Oliver, L., Boyd, C., & Rosenbloom, J. (1984) Biochem. Biophys. Res. Commun. 118, 261-269] [15].
• Genomic clones encompassing all the translated sequences, the 3' untranslated sequence, and 1 kb flanking the ATG translation initiation codon of bovine tropoelastin have been obtained and characterized by restriction enzyme analysis and extensive DNA sequencing [23].
• The ability of tropoelastin to associate with preexisting elastic fibers or microfibrils in the extracellular matrix was then assessed by immunofluorescence microscopy using species-specific tropoelastin antibodies [13].

References