Disease relevance of Eln

• Elastase/anti-elastase imbalance is a hallmark of emphysema, a chronic obstructive pulmonary disease associated with the rupture and inefficient repair of interstitial elastin [1].
• While elastin degradation is a hallmark of pulmonary emphysema, it is likely that elastin synthesis also occurs [2].
• Differences in elastin organisation are, therefore, a central element in small artery remodelling in hypertension [3].
• In parallel with downregulation of the destructive process, active TGF-beta1 overexpression triggered endoluminal reconstruction, replacing the thrombus by a vascular smooth muscle cell-, collagen-, and elastin-rich intima [4].
• BACKGROUND: Arterial aneurysms exhibit a loss of elastin and an increase in the plasminogen activators urokinase plasminogen activator (u-PA) and tissue plasminogen activator (t-PA) [5].

Psychiatry related information on Eln

• These observations demonstrate that long-term alcohol consumption up-regulates MMP-2 activity, which is coincident with the alteration of aortic ECM composition through the degradation of vascular elastin components [6].

High impact information on Eln

• Degradation of connective tissue matrices by macrophages. II. Influence of matrix composition on proteolysis of glycoproteins, elastin, and collagen by macrophages in culture [7].
• Both live macrophages and their conditioned media hydrolyzed glycoproteins, elastin, and collagen [7].
• Thus, although plasmin has no direct elastinolytic activity, its presence accelerated the rate of hydrolysis of elastin and therefore the rate of matrix degradation [7].
• Tropoelastin, type I procollagen and TGF-beta gene expression, and angiotensin converting enzyme immunoreactivity, was confined to the neointima resembling the pattern of gene expression and immunoreactivity in human hypertensive elastic pulmonary artery neointimal lesions [8].
• Strain increased DNA synthesis in cells on collagen, fibronectin, or vitronectin, but not in cells on elastin or laminin [9].

Chemical compound and disease context of Eln

• The prevention of arterial stiffening and cardiac hypertrophy in the absence of changes in collagen and elastin content suggests that the effect of aminoguanidine is related to a decrease in the AGE-induced cross-linking of the extracellular matrix [10].
• SC-39026 did not significantly reduce monocrotaline-induced medial hypertrophy of muscular arteries, endothelial injury, and associated subendothelial edema; nor was there a significant increase in the proportion of the medial elastin, although a trend was apparent [11].
• The concentration of IDP was significantly elevated in aorta elastin of rat with chronic liver cirrhosis induced by carbon tetrachloride (mean +/- S.D.; 11.1 +/- 0.9 nmol/mg elastin) when compared with normal rats (5.9 +/- 1.5 nmol/mg elastin) [12].
• Effect of vitamin B-6 (pyridoxine) deficiency on lung elastin cross-linking in perinatal and weanling rat pups [13].
• Pulmonary fibrosis was assessed biochemically by measuring pulmonary elastin and hydroxyproline content [14].

Biological context of Eln

• Exogenous and endogenous transforming growth factors-beta influence elastin gene expression in cultured lung fibroblasts [15].
• Transient transfection experiments using an elastin promoter/CAT gene construct demonstrated that bFGF exposure decreased elastin promoter activity [16].
• Since others have shown that elastin mRNA appears to have a longer half-life in neonatal than in adult rat lungs, we hypothesize that the higher content of TGF-beta s could contribute to the greater elastin mRNA stability in neonatal lungs [15].
• Because alveolar septal elongation is accompanied by a decrease in capillary endothelial cell mitosis, we have hypothesized that a reduction in basic fibroblast growth factor (bFGF), an endothelial cell mitogen, may occur concomitantly with an increase in elastin synthesis [16].
• Nuclear run-on analyses demonstrate that the downregulation is due to a decrease in the level of elastin gene transcription [17].

Anatomical context of Eln

• During pulmonary development, there is a burst in elastin synthesis by interstitial fibroblasts coincident with the period of alveolar septal elongation [16].
• Basic fibroblast growth factor decreases elastin gene transcription in aortic smooth muscle cells [17].
• The extracellular matrix (ECM) protein elastin plays an essential role in the cardiovascular system by imparting elasticity to blood vessel wall [17].
• Very little is known about the regulation of elastin synthesis during the development of emphysema when prominent collections of mononuclear phagocytes are found in and near the alveolar interstitium [2].
• The aim of our study was to explore the localization of elastin mRNA and TGF-beta1 in the rat thoracic aorta (an elastic artery) and caudal artery (a muscular artery) [18].

Associations of Eln with chemical compounds

• Based on known tropoelastin sequences and the molecular weights of the discrete fragments, additional fragmentation of protropoelastin and/or tropoelastin most likely occurs at the lysine/alanine-enriched domains presumably involved in cross-link formation [19].
• Since cysteine is present only in the carboxyl-terminal end of the molecule, all the data indicate that the cleavage of the elastin fragments identified in the culture are occurring at the carboxyl end of protropoelastin [19].
• All soluble elastin components present in the medium were purified as a single peak by high performance liquid chromatography; further separation of the components was achieved by polyacrylamide gel electrophoresis and electroblotting [19].
• METHODS: Rat MCs cultured in media containing either 8 or 35 mM glucose were seeded into culture plates with elastin-coated flexible bottoms [20].
• Resected lungs were stained with hematoxylin and eosin, Masson's trichrome, and Van Gieson's elastin, and immunostained with antisera to interleukin (IL)-1beta, IL-8, and basic fibroblast growth factor (bFGF) [21].

Physical interactions of Eln

• In the present study we investigated whether matrix metalloproteinase (MMP) binding to elastin and elastin degradation is prevented by AlCl(3) pretreatment [22].

Enzymatic interactions of Eln

• Lysyl oxidase catalyzes the crosslinking of collagen and elastin [23].

Co-localisations of Eln

• Gene expression for all three isoforms of TGF-beta colocalized with tropoelastin gene expression along the vascular lumen but not with alpha 1(I) procollagen gene expression [24].

Regulatory relationships of Eln

• Our studies indicate that exogenous and endogenous bFGF can suppress elastin production by LF [16].
• We hypothesized that TGF-beta may influence elastin production by fibroblasts in the pulmonary interstitium [2].
• Also, neutralizing antibodies to TGF-beta 3 blocked the cortisol-stimulated TE mRNA expression [25].
• Moreover, elastin gel zymography studies showed that gel pretreatment with AlCl(3) inhibited elastolysis by MMP-9 [22].
• Combined in situ hybridization and immunocytochemistry reveals that most elastin mRNA-expressing cells in the media are alpha-actin-positive smooth muscle cells [26].

Other interactions of Eln

• These findings indicate that endogenous TGF-beta s, in cultured LF, regulate elastin gene expression, most likely by a posttranscriptional mechanism [15].
• These results suggest that bFGF decreases elastin transcription [16].
• The addition of PD-98059, an inhibitor of ERK1/2 kinase, abrogates the bFGF-dependent decrease of elastin mRNA in SMC [17].
• Elastin degradation associated with matrix metalloproteinase activity is a cell-mediated process, observed in almost all types of vascular calcification [27].
• Using RT-PCR and specific protein assays, we demonstrated that rat aortic SMCs incubated with elastin peptides exhibited an increased expression of the 67 kDa elastin laminin receptor (ELR) and matrix metalloproteinase-2 and typical bone proteins, such as core binding factor alpha-1, osteocalcin, and alkaline phosphatase [27].

Analytical, diagnostic and therapeutic context of Eln

• Elastin mRNA was localized by in situ hybridization and quantified using Northern blot analysis [18].
• As expected, when the cell cultures were pulsed with [3H]valine, all the soluble elastin molecules were radioactive, while only protropoelastin appeared radioactive after [35S] cysteine pulsing [19].
• In situ hybridization demonstrated tropoelastin gene expression by cells adjacent to the lumen and procollagen gene expression at the medial-adventitial border in both small muscular and large elastic pulmonary arteries [24].
• Confocal microscopy was used to determine differences in the quantity and organisation of elastin in intact pressure-fixed arteries [3].
• Sequence analysis of these clones has provided the complete derived amino acid sequence of rat tropoelastin and allowed alignment and comparison with published bovine cDNA sequence [28].

References