Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously characterized two normotensive strains of rats which differ markedly in their susceptibility to spontaneous rupture of the internal elastic lamina (IEL), the Brown Norway (BN) being very susceptible and the Long Evans (LE) being resistant. Here we quantified biochemically the elastin and collagen content of aortae from adult male BN and LE rats aged 12, 18 and 22 weeks and showed that the elastin content was lower and the collagen content higher in the BN strain than in the LE strain, resulting in a markedly lower elastin/collagen ratio in the former strain. These modifications were present both in the thoracic aorta, which is devoid of IEL ruptures, and in the abdominal segment where ruptures frequently occur in the BN rat, suggesting that they could represent a predisposing factor in the presence of other local factors. Quantifications of relevant mRNAs in aortae of younger male BN and LE rats by Northern blot showed that there are lower tropoelastin transcript levels in the BN rat at 6 weeks in both thoracic and abdominal segments than in the age-matched LE rat. In contrast there was no consistent interstrain difference in alpha 1 type I collagen transcripts and alpha 1 type III collagen transcripts were higher in the BN aorta only at 6 weeks in the abdominal segment. We conclude that the BN rat presents an aortic elastin deficit which appears to be in part explained by a decreased elastin synthesis in young, growing rats and may be genetically determined. However, a direct relation of this elastin deficit with susceptibility to rupture of the IEL cannot be concluded from this study.
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PMID:Aortic elastin and collagen content and synthesis in two strains of rats with different susceptibilities to rupture of the internal elastic lamina. 916 45

Young and old (4 and 25 months of age, respectively) Fisher 344/Brown Norway hybrid female rats were subjected to four 3 min episodes of ischemia separated by 5 min of reperfusion. Corresponding open-chest sham-operated groups received 32 min of no intervention. All rats were allowed to recover, and 24h later hearts were removed and frozen in liquid nitrogen. Global gene profiling in the ischemic and the non-ischemic areas and in the sham-operated hearts as well was carried out by using Affymetrix Gene Chips. Young ischemic hearts demonstrated down-regulation of gene expression associated with early-remodeling including down-regulation of tissue inhibitor of metalloproteinase 1, decorin, collagen, tropoelastin, and fibulin, as well as decreases in hypertrophy-related transcripts. In contrast, old hearts showed a unique injury-related response, which included up-regulation of mRNAs for proteins associated with hypertrophy or apoptosis (including H36-alpha7 integrin, alpha-actin, tubulin, filamin, connective tissue growth factor, calcineurin, serine protease, and apoptosis inducing factor). These injury-related changes in gene expression could in part explain increased gravity of outcomes of ischemia and myocardial infarction in elderly hearts.
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PMID:Age-related changes of cardiac gene expression following myocardial ischemia/reperfusion. 1465 66

Extracellular matrix molecules such as elastin and collagens provide mechanical support to the vessel wall. In addition to its structural role, elastin is a regulator that maintains homeostasis through biologic signaling. Genetically determined minor modifications in elastin and collagen in the aorta could influence the onset and evolution of arterial pathology, such as hypertension and its complications. We previously demonstrated that the inbred Brown Norway (BN) rat shows an aortic elastin deficit in both abdominal and thoracic segments, partly because of a decrease in tropoelastin synthesis when compared with the LOU rat, that elastin gene polymorphisms in these strains do not significantly account for. After a genome-wide search for quantitative trait loci (QTL) influencing the aortic elastin, collagen, and cell protein contents in an F2 population derived from BN and LOU rats, we identified on chromosomes 2 and 14, 3 QTL specifically controlling elastin levels, and a further highly significant QTL on chromosome 17 linked to the level of cell proteins. We also mapped 3 highly significant QTL linked to body weight (on chromosomes 1 and 3) and heart weight (on chromosome 1) in the cross. This study demonstrates the polygenic control of the content of key components of the arterial wall. Such information represents a first step in understanding possible mechanisms involved in dysregulation of these parameters in arterial pathology.
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PMID:Chromosomal mapping of quantitative trait loci controlling elastin content in rat aorta. 1566 57

The extracellular matrix (ECM) plays an important role in vascular tissue structure, maintenance, and function. Lysyl oxidases catalyze a key step in the posttranslational cross-linking of elastin and collagens in the ECM. Gene knockout studies in mice suggested a role for lysyl oxidase-like (LOXL1) in adult elastin synthesis and a role for its isoform, lysyl oxidase (LOX), in the synthesis of both collagens and elastin during development. However, the relative expression of both isoforms as a function of age is not known and was therefore investigated here. LOX and LOXL1 immunohistochemistry and real-time RT-PCR were performed during development, growth and aging in the aorta of LOU and Brown-Norway (BN) rats, two inbred strains with different susceptibilities to arterial fragility. In addition, expression of genes encoding for elastic fiber proteins and type I collagen, together with elastin and collagen contents, was measured in adult and old rat aortas. High aortic LOX expression was observed early in the development (embryonic day 15), followed by a drastic reduction in adulthood, whereas LOXL1 was mainly detectable in the intima and media; its expression was maintained throughout life in the LOU rat. Expression of tropoelastin, type-I collagen, and LOXL1 genes was reduced in the aorta of 6-week-old BN rats. Aging is characterized by a decreased elastin/collagen ratio and a greatly decreased expression of LOX, tropoelastin, and type-I collagen. These findings indicate a different spatial and temporal expression of LOX and LOXL1 during growth and aging in the rat aorta and suggest specific roles for LOX and LOXL1 in the synthesis and remodeling of elastic and collagen fibers.
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PMID:Differential expression of lysyl oxidases LOXL1 and LOX during growth and aging suggests specific roles in elastin and collagen fiber remodeling in rat aorta. 1880 61

Hypertension is a cardiovascular disorder that appears in more than half of the patients with Williams-Beuren syndrome, hemizygous for the elastin gene among 26 to 28 other genes. It was shown that the antihypertensive drug minoxidil, an ATP-dependent potassium channel opener, enhances elastic fiber formation; however, no wide clinical application was developed because of its adverse side effects. The Brown Norway rat was used here as an arterial elastin-deficient model. We tested 3 different potassium channel openers, minoxidil, diazoxide, and pinacidil, and 1 potassium channel blocker, glibenclamide, on cultured smooth muscle cells from Brown Norway rat aorta. All tested potassium channel openers increased mRNAs encoding proteins and enzymes involved in elastic fiber formation, whereas glibenclamide had the opposite effect. The higher steady-state level of tropoelastin mRNA in minoxidil-treated cells was attributable to an increase in both transcription and mRNA stability. Treatment of Brown Norway rats for 10 weeks with minoxidil or diazoxide increased elastic fiber content and decreased cell number in the aortic media, without changing collagen content. The minoxidil-induced cardiac hypertrophy was reduced when animals simultaneously received irbesartan, an angiotensin II-receptor antagonist. This side effect of minoxidil was not observed in diazoxide-treated animals. In conclusion, diazoxide, causing less undesirable side effects than minoxidil, or coadministration of minoxidil and irbesartan, increases elastic fiber content, decreases cell number in the aorta and, thus, could be suitable for treating vascular pathologies characterized by diminished arterial elastin content and simultaneous hypertension.
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PMID:Potassium channel openers increase aortic elastic fiber formation and reverse the genetically determined elastin deficit in the BN rat. 2391 51