Marginal copper deficiency in rats aortal morphology of elastin and cholesterol values in first-generation adult males

Hunsaker, Harry A.; Morita, Michio; Allen, Kim

doi:10.1016/0021-9150(84)90140-0

Cited by 37 publications

(9 citation statements)

References 42 publications

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“…No ultrastructural report has been available on the arteries of copper-deficient deer or their elastic fibrous disorder. Morphological changes such as fragmentation and irregular clumps of elastic fibers, as pointed out in the present study, are similar to the findings in pigs [4,25,26,27], chickens [2,15,17,21,24], rats [12] and rabbit [13] in experimental copper deficiency. The major protein constituting elastic fibers of the aortic wall is elastin, which corresponds to 50% of the dry weight of the aorta [1].…”

supporting

confidence: 79%

Ultrastructure of Aortic Elastic Fibers in Copper-Deficient Sika Deer(Cervus nippon Temminck).

Yoshikawa

Wang²,

Seo

et al. 2001

The Journal of Veterinary Medical Science

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ABSTRACT. Light microscopic and transmission and scanning electron microscopic observations were performed on the aortas of two 4-and 6-year-old deer affected with cervine ataxia and two 6-month-and 4-year-old healthy deer. Examination of the aortas from affected deer by transmission electron microscopy revealed the absence of distinct elastic laminae in the internal elastic lamina and tunica media, but discontinuous and irregular clumps of elastin were present. Scanning electron microscopy disclosed immature architecture of elastic fibers in the aortas from the copper-deficient deer, and the architecture was similar to that of a 6-month-old healthy deer.

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supporting

confidence: 79%

Ultrastructure of Aortic Elastic Fibers in Copper-Deficient Sika Deer(Cervus nippon Temminck).

Yoshikawa

Wang²,

Seo

et al. 2001

The Journal of Veterinary Medical Science

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“…41 Deficiency of nutritional copper has been linked to vascular lesions and development of aneurysms. [42][43][44] One study showed that, in the presence of HA, low doses (0.01 M) of CuSO 4 enhance tissue vascularization. 45 Dahl et al investigated the singular effects of increasing medium Cu 2þ ion concentration on matrix crosslinking efficiency in an engineered vascular-like tissue and showed that increasing levels of cross-links formed.…”

Section: Discussionmentioning

confidence: 99%

Biomimetic Regeneration of Elastin Matrices Using Hyaluronan and Copper Ion Cues

Kothapalli

Ramamurthi

2009

Tissue Engineering Part A

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Current efforts to tissue engineer elastin-rich vascular constructs and grafts are limited because of the poor elastogenesis of adult vascular smooth muscle cells (SMCs) and the unavailability of appropriate cues to upregulate and enhance cross-linking of elastin precursors (tropoelastin) into organized, mature elastin fibers. We earlier showed that hyaluronan (HA) fragments greatly enhance tropo-and matrix-elastin synthesis by SMCs, although the yield of matrix elastin is low. To improve matrix yields, here we investigate the benefits of adding copper (Cu 2+ ) ions (0.01 M and 0.1 M), concurrent with HA (756-2000 kDa), to enhance lysyl oxidase (LOX)-mediated elastin cross-linking machinery. Although absolute elastin amounts in test groups were not different from those in controls, on a per-cell basis, 0.1 M of Cu 2+ ions slowed cell proliferation (5.6 AE 2.3-fold increase over 21 days vs 22.9 AE 4.2-fold for non-additive controls), stimulated synthesis of collagen (4.1 AE 0.4-fold), tropoelastin (4.1 AE 0.05-fold) and cross-linked matrix elastin (4.2 ± 0.7-fold). LOX protein synthesis increased 2.5 times in the presence of 0.1 M of Cu 2+ ions, and these trends were maintained even in the presence of HA fragments, although LOX functional activity remained unchanged in all cases. The abundance of elastin and LOX in cell layers cultured with 0.1 M of Cu 2+ ions and HA fragments was qualitatively confirmed using immunoflourescence. Scanning electron microscopy images showed that SMC cultures supplemented with 0.1 M of Cu 2+ ions and HA oligomers and large fragments exhibited better deposition of mature elastic fibers (*1 mm diameter). However, 0.01 M of Cu 2+ ions did not have any beneficial effect on elastin regeneration. In conclusion, the results suggest that supplying 0.1 M of Cu 2+ ions to SMCs to concurrently (a) enhance per-cell yield of elastin matrix while allowing cells to remain viable and synthetic and not density-arrested in long-term culture because of their moderating effects on otherwise rapid cell proliferation and (b) provide additional benefits of enhanced elastin fiber formation and cross-linking within these tissue-engineered constructs.

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“…Decreased lysyl oxidase activity may re sult from copper deficiency, and it has been demonstrated that in the rat, marginal cop per deficiency, starting in utero will elicit minor structural abnormalities involving the elastic fibers and notably the IEL in aortae of rats showing no overt signs of copper defi ciency [14]. In a previous study we did not observe a marked effect of dietary copper supplementation on the formation of IEL interruptions in the Wistar rat [6], but we cannot rule out the possibility that some abnormality of copper metabolism may be involved.…”

Section: Discussionmentioning

confidence: 99%

Spontaneous Rupture of the Internal Elastic Lamina in the Rat: The Manifestation of a Genetically Determined Factor Which May Be Linked to Vascular Fragility

Capdeville

Coutard²,

Osborne-Pellegrin³

1989

J Vasc Res

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The spontaneous rupture of the internal elastic lamina (IEL) in various arteries occurs to different extents in different rat strains. We have quantified this phenomenon in the caudal and renal arteries and abdominal aorta in two normotensive inbred strains: the Brown Norway (BN) and Long Evans (LE) strains. At 5 weeks of age, BN rats of both sexes exhibited small numbers of interruptions in the IEL of the caudal artery, whereas LE rats did not. Postpubertal male and female BN rats presented large numbers of IEL interruptions in the caudal artery and significant numbers in the renal artery and abdominal aorta, whereas LE rats showed few in the caudal artery and none in the other arteries. Treatment with β -aminopropionitrile (BAPN, an inhibitor of lysyl oxidase, the enzyme involved in the formation of cross-links in elastin and collagen) increased the formation of IEL ruptures in both strains in the caudal and renal artery and in the abdominal aorta in BN rats, but not in the abdominal aorta of LE rats. Apart from IEL ruptures, which were more prevalent in BN rats, no differences were observed in the ultrastructure of the aortic elastic fibers between the two strains, either in controls or in BAPN-treated rats. When male rats of both strains were made hypertensive by unilateral nephrectomy and administration of deoxycorticosterone and salt, mortality was more precocious in the BN strain although blood pressure was significantly higher in the BN strain at only one time point. The incidence of cerebrovascular hemorrhage was 48% in BN rats and 0% in LE rats. Hypertension increased the formation of ruptures in the IEL in some arteries – to a greater extent in the BN than in the LE rats. These results raise the possibility that the propensity to spontaneous rupture of the IEL, which is in part genetically determined, may reflect a latent form of vascular fragility which becomes significant in hypertension, resulting in poor survival and susceptibility to cerebrovascular accidents.

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Marginal copper deficiency in rats aortal morphology of elastin and cholesterol values in first-generation adult males

Cited by 37 publications

References 42 publications

Ultrastructure of Aortic Elastic Fibers in Copper-Deficient Sika Deer(Cervus nippon Temminck).

Ultrastructure of Aortic Elastic Fibers in Copper-Deficient Sika Deer(Cervus nippon Temminck).

Biomimetic Regeneration of Elastin Matrices Using Hyaluronan and Copper Ion Cues

Spontaneous Rupture of the Internal Elastic Lamina in the Rat: The Manifestation of a Genetically Determined Factor Which May Be Linked to Vascular Fragility

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