9 replies to this topic

[Lufega]

These just some studies I found relating to elastin production. Most of the focus on elastin seem to be on topical applications of increasing elastase but it seems that regulating vitamin/mineral status is also important. An example of this is magnesium and vitamin K.

Relationship between magnesium and elastic fibres.

Institute of Pathology, University of Cologne, Germany.

The presence of magnesium was demonstrated by histochemical methods in elastic fibres from different locations. After pretreatment with elastase a positive reaction could no longer be detected. Microfibrils which enclose the elastin core of the elastic fibres gave no positive reaction. These results support the supposition of a close relationship between Mg and elastin. Determination of the Ca/Mg ratio by atomic absorption spectrometry in variants of fibrous connective tissue showed a decreasing Ca level with increasing elasticity. The Ca/Mg ratio in lattices containing rubber-like particles disclosed striking diminution of Ca. These data support the speculation that the antagonism of Mg to Ca plays a fundamental role in the maintenance of elasticity. The special interaction of the Mg2+ ion with water molecules is very probably a further prerequisite for elasticity in natural elastic materials.

PMID: 8292494

Effect of vitamin B-6 (pyridoxine) deficiency on lung elastin cross-linking in perinatal and weanling rat pups.Weanling and perinatal rats were rendered vitamin B-6 (pyridoxine)-deficient. The rat pups were nursed from vitamin B-6-deficient or -sufficient dams and were killed at day 15 after parturition. The weanling rats were fed vitamin B-6-deficient or -sufficient diets and were killed after 5 weeks of treatment. Lung elastin from the groups of rats was then studied with respect to its content of lysine-derived cross-linking amino acids. Lung lysyl oxidase activity was also measured. B-6 deficiency decreased the number of lysine residues in elastin that were converted into the cross-linking amino acid precursor allysine. However, a more significant defect in cross-link formation was an apparent block in the condensation steps leading to the formation of desmosine. Desmosine was decreased, with an increase in the amounts of aldol condensation products (aldol CP) in elastin. It is proposed that the elevation in aldol CP results from the formation of thiazines, which are produced from the reaction between aldehyde and homocysteine. The concentration of homocysteine is significantly elevated in vitamin B-6-deficient rats.

PMID: 2864042

Vitamin B6 deficiency affects lung elastin crosslinking

PMID: 3951762

Vitamin K deficit affect mucopolyssacharide (glycosaminoglycans) status.

[Metabolic indices in the connective tissue in experimental hyper- and hypovitaminosis K]

Sharaev PN.

In experiments on rats the content of acid mucopolysaccharides (AMPS), collagen and elastin in a variety of the connective tissue--in the aorta of rats with hyper- and hypovitaminosis K was studied. In hypervitaminosis K no changes in the aortic wall were revealed. Hypovitaminosis produced by a special ration and pelentan was attended by a fall in the levels of AMPS and collagen. The elastin content reamained unchanged.

PMID: 149021 [PubMed - indexed for MEDLINE]

This study says elastin is low in vitamin K deficit even low K decreases elastase activity.

[Elastin metabolic indices in various body allowances of vitamin K] [Article in Russian]

Sharaev PN.

A study was made of the content of insoluble elastin in the tissues and of elastolytic activity of the blood serum at varying supply of the rat body with vitamin K. It was revealed that long-term (for 1 month) excess administration of vicasol (10 mg/kg) did not change elastin metabolism. In the course of the development of alimentary K-avitaminosis, blood elastolytic activity was first inhibited and then dramatically rose (by 93.4%). The latter finding was in a good agreement with a decrease in the level of insoluble elastin in the aorta wall and skin. After exposure of rats to pelentan, an antagonist of vitamin K, for 15-20 days the activity of the enzymes responsible for elastin breakdown was steadily inhibited. Nevertheless the skin elastin content decreased by 16.1%. It has been shown that the reduction of the elastin content in the connective tissue is not related to the changes in the diet. The evidence obtained attests to the involvement of vitamin K in elastin metabolism.

Excess calcium and cholesterol degrades elastin and promotes atherosclerosis. Vitamin K is therapeutic.

Atherosclerosis and matrix dystrophy.

Department of Clinical Chemistry, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan. seyama@hoshi.ac.jp

Atherosclerosis is characterized by inflammatory metabolic change with lipid accumulation in the artery. Atherosclerotic plaque occurs at discrete locations in the arterial system and involves the proliferation of smooth muscle cells (SMCs) together with imbalance of the extracellular matrix elements, elastic fiber in particular. The role of elastin in arterial development and disease was confirmed by generating mice that lack elastin. Thus, elastin is a critical regulatory molecule that regulates the phenotypic modulation, proliferation and migration of SMCs.


We estimated that elastin expression and SMC proliferation are coupled inversely: potent stimulators of cell proliferation may potentially inhibit elastin expression and potent inhibitors of cell proliferation can stimulate elastin expression. Moreover, elastin was found to be expressed maximally at the G(0) and minimally at the G(2)/M phase during the cell cycle, suggesting that its expression is regulated by the cell growth state. The elastin peptide VPGVG enhanced SMC proliferation, resulting in the reduction of elastin expression. The inhibition of elastin expression by elastin fragments may be reflected in the negative feedback regulatory mechanism. The relationship between cell proliferation and elastin expression may be changed in atherosclerosis. Areas of atherosclerotic plaque show abnormality of elasticity and permeability from the viewpoint of the physiological function of the arterial wall. The etiology was estimated to be that cholesterol and calcium are deposited on the elastic fiber, resulting in decreased elastin synthesis and cross-linking formation. In addition, these dysfunctions of elastin fiber are also associated, in that the down-regulation of elastin and its related components (fibrillin-1 and lysyl oxidase) are directly related to calcification in SMCs. The denatured arterial elastin by cholesterol and calcium accumulation was also susceptible to proteolytic enzymes such as elastase and matrix metalloproteinase (MMP). Therefore, metabolic change in elastic fiber induces decreased elasticity and is associated with essential hypertension. Vitamin K(2) is used in drug therapy against atherosclerosis, or calcification in diabetes mellitus or dialysis, due to its promotion of the carboxylation of the matrix Gla protein.

I would love to read the full study of this last one.

You can see how all these nutrients are related. Vitamin B6 is needed for magnesium to do its job. Magnesium antagonizes excess calcium and aids in its tranport to bone, much similiar to vitamin K. All these also affect elastin when in insufficient amounts.

Edited by Lufega, 25 April 2010 - 07:19 PM.

[mustardseed41]

http://www.smart-pub.../vitamin_k2.php

[rwac]

Vitamin C deficiency in guinea pigs differentially affects the expression of type IV collagen, laminin, and elastin in blood vessels.

Mahmoodian F, Peterkofsky B.

Abstract
Vitamin C deficiency causes morphologic changes in the endothelial and smooth muscle compartments of guinea pig blood vessels. Endothelial cells synthesize the basement membrane components, type IV collagen and laminin, and smooth muscle cells synthesize elastin in blood vessels. Therefore, we examined the possibility that vitamin C deficiency affects the expression of these proteins. Decreased expression of types I and II collagens in other tissues of vitamin C-deficient guinea pigs is associated with weight loss and the consequent induction of insulin-like growth factor binding proteins; thus we also used food deprivation to induce weight loss. Female guinea pigs received a vitamin C-free diet, supplemented orally with ascorbate. Vitamin C-deficient guinea pigs received the same diet but no ascorbate, and the food-deprived group received no food, but were supplemented with vitamin C. Concentrations of mRNAs for basement membrane components and elastin in blood vessels were measured by Northern blotting; overall basement membrane metabolism was assessed by measuring immunoreactive laminin and type IV 7S collagen in serum. Laminin mRNA in blood vessels and serum laminin concentrations were unaffected by vitamin C deficiency. Concentrations of type IV collagen and elastin mRNAs in blood vessels were not significantly affected in moderately scorbutic guinea pigs (0-7% weight loss), but with increased weight loss, type IV collagen mRNA was 57% (P < 0.05) and elastin mRNA was 3% (P < 0. 01) of normal values. In food-deprived guinea pigs, type IV collagen mRNA was 51% (P < 0.05) and elastin mRNA was 35% (P < 0.05) of normal. Serum type IV 7S collagen concentrations were 25% of normal in scorbutic guinea pigs with extensive weight loss. The lower expression of type IV collagen and elastin mRNAs in blood vessels may contribute to defects observed in blood vessels during scurvy.

PMID: 9915880 [PubMed - indexed for MEDLINE]Free Article

Skin atrophy in cytoplasmic SOD-deficient mice and its complete recovery using a vitamin C derivative.

Murakami K, Inagaki J, Saito M, Ikeda Y, Tsuda C, Noda Y, Kawakami S, Shirasawa T, Shimizu T.

Abstract

Intrinsic skin ageing is characterized by atrophy and loss of elasticity. Although the skin hypertrophy induced by photoageing has been studied, the molecular mechanisms of skin atrophy during ageing remain unclear. Here, we report that copper/zinc superoxide dismutase (CuZn-SOD)-deficient mice show atrophic morphology in their skin. This atrophy is accompanied by the degeneration of collagen and elastic fibers, and skin hydroxyproline is also significantly reduced in deficient mice. These imply that the dysfunction of collagen and elastin biosynthesis are involved in the progression of skin thinning. Furthermore, transdermal administration of a vitamin C derivative which can permeate through the membrane, completely reversed the skin thinning and deterioration of collagen and elastin in the mutant mice. These indicate that the vitamin C derivative is a powerful agent for alleviating skin ageing through regeneration of collagen and elastin. The CuZn-SOD-deficient mice might be applicable to evaluation of therapeutic medicines against skin ageing.

PMID: 19289104

No Abstract for this one, but it looks interesting.

Role of selected nutrients in synthesis, accumulation, and chemical modification of connective tissue proteins.

Effect of Mg2+ and Ca2+ on enzymatic elastolysis of insoluble elastin determined by a conductimetric method.

Bernier F, Bakala H, Wallach J.
Abstract

The effect of some divalent cations on the elastolysis of insoluble elastin by pancreatic elastase has been studied with a conductimetric method. Mn2+ and Cu2+ give progressive inhibition, while Ca2+ initially slightly increases elastolysis, then becomes an inhibitor at concentrations higher than 10(-4) M. A stronger effect is demonstrated with Mg2+ which increases the initial velocity of the enzymatic reaction. However, there is no effect when N-succinyl-(Ala)(3)-paranitroanilide is used as the substrate. The different effects observed can be explained by an enzymatic activation process (cation-enzyme complex) and/or by a conformational change of the insoluble elastin.

PMID: 6453692

[Lufega]

No Abstract for this one, but it looks interesting.

Role of selected nutrients in synthesis, accumulation, and chemical modification of connective tissue proteins.

Found the first page of the PDF.

http://physrev.physi...xtract/65/3/607

It even mentions the effect of calorie restriction on connective tissue. I would love to read the full study.

[Lufega]

Soy seems to be demonized here but it seems to function in favor of everything elastin.

* Induces Elastin synthesis
* Inhibits elastase

Extracts from Glycine max (soybean) induce elastin synthesis and inhibit elastase activity.

Zhao R, Bruning E, Rossetti D, Starcher B, Seiberg M, Iotsova-Stone V.
Abstract

Elastic fibres are essential extracellular matrix components of the skin, contributing to its resilience and elasticity. In the course of skin ageing, elastin synthesis is reduced, and elastase activity is accelerated, resulting in skin sagging and reduced skin elasticity. Our studies show that non-denatured Glycine max (soybean) extracts induced elastin promoter activity, inhibited elastase activity and protected elastic fibres from degradation by exogenous elastases in vitro. Mouse and swine skins topically treated with soybean extracts showed enhanced elastic fibre network and increased desmosine content. Elastin expression was also augmented in human skin transplanted onto SCID mice in response to soy treatment. These data suggest that non-denatured soybean extracts may be used as skin care agents to reduce the signs of skin ageing.

PMID: 19469891 [PubMed - indexed for MEDLINE]

Which extract are they referring to? Isoflavones? Genistein?

[Denjin]

How about lutein as well? There are a few articles in pubmed as well as some other bits on the internet...

[Lufega]

Ellagic acid helps preserve already existing Elastin from proteolytic degradation.

Ellagic and tannic acids protect newly synthesized elastic fibers from premature enzymatic degradation in dermal fibroblast cultures.
Jimenez F, Mitts TF, Liu K, Wang Y, Hinek A.

Research Department, Human Matrix Sciences, LLC, Visalia, California, USA.


Abstract
Progressive proteolytic degradation of cutaneous elastic fibers, that cannot be adequately replaced or repaired by adult dermal fibroblasts, constitutes a major feature of aging skin. Our present investigations, employing monolayer cultures of human dermal fibroblasts and organ cultures of skin biopsies, were aimed at testing whether the hydrophilic tannic acid (TA) and lipophilic ellagic acid (EA) would protect dermal elastin from exogenous and endogenous enzymatic degradation. Results from both culture systems indicated that dermal fibroblasts, maintained with TA or EA, deposit significantly more elastic fibers than untreated control cultures despite the fact that neither polyphenol enhanced transcription of elastin mRNA or cellular proliferation. Results of a pulse and chase experiment showed that pretreatment with both polyphenols enhanced biostability of tropoelastin and newly deposited elastin. Results of in vitro assays indicated that both polyphenols bound to purified elastin and significantly decreased its proteolytic degradation by elastolytic enzymes belonging to the serine proteinase, cysteine proteinase, and metallo-proteinase families. Importantly, both polyphenols also synergistically enhanced elastogenesis induced by selected elastogenic compounds in cultures of dermal fibroblasts. We propose that EA and TA may be useful for preventing proteolytic degradation of existing dermal elastic fibers and for enhancing more efficient elastogenesis in aged skin.

Full Study : http://www.nature.co...df/5700285a.pdf

[Lufega]

Aldosterone increases production of collagen and elastin. Licorice is something that can increase levels of this.

Aldosterone stimulates elastogenesis in cardiac fibroblasts via mineralocorticoid receptor-independent action involving the consecutive activation of Galpha13, c-Src, the insulin-like growth factor-I receptor, and phosphatidylinositol 3-kinase/Akt.
Bunda S, Wang Y, Mitts TF, Liu P, Arab S, Arabkhari M, Hinek A.

Physiology and Experimental Medicine Program, The Hospital for Sick Children, Department of Laboratory Medicine and Pathobiology, Heart and Stroke/Richard Lewar Centre for Excellence, University of Toronto, Toronto, Ontario, Canada.


Abstract
We previously demonstrated that aldosterone, which stimulates collagen production through the mineralocorticoid receptor (MR)-dependent pathway, also induces elastogenesis via a parallel MR-independent mechanism involving insulin-like growth factor-I receptor (IGF-IR) signaling. The present study provides a more detailed explanation of this signaling pathway. Our data demonstrate that small interfering RNA-driven elimination of MR in cardiac fibroblasts does not inhibit aldosterone-induced IGF-IR phosphorylation and subsequent increase in elastin production. These results exclude the involvement of the MR in aldosterone-induced increases in elastin production. Results of further experiments aimed at identifying the upstream signaling component(s) that might be activated by aldosterone also eliminate the putative involvement of pertussis toxin-sensitive Galphai proteins, which have previously been shown to be responsible for some MR-independent effects of aldosterone. Instead, we found that small interfering RNA-dependent elimination of another heterotrimeric G protein, Galpha13, eliminates aldosterone-induced elastogenesis. We further demonstrate that aldosterone first engages Galpha13 and then promotes its transient interaction with c-Src, which constitutes a prerequisite step for aldosterone-dependent activation of the IGF-IR and propagation of consecutive downstream elastogenic signaling involving phosphatidylinositol 3-kinase/Akt. In summary, the data we present reveal new details of an MR-independent cellular signaling pathway through which aldosterone stimulates elastogenesis in human cardiac fibroblasts.

[Lufega]

Also, anything that increases IGF-1 pretty much upregulated nuclear transcription of elastin. Aldosterone itself works by sensitizing IGF-1 receptors. Substances that I found that can increase IGF-1 and affect elastin are capsaicin and biotin.

[Alec]

I'm guessing that this is going to surprise a few people. According to this study, the addition of iron may be good for increasing elastin. Very good in fact. But it seems that as the amount of iron increases so does the need for hydroxyl radical scavengers.

Fluctuations of Intracellular Iron Modulate Elastin Production

Bunda S, Kaviani N, Hinek A.

Cardiovascular Research Program, The Hospital for Sick Children and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5G 1X8, Canada.

Production of insoluble elastin, the major component of elastic fibers, can be modulated by numerous intrinsic and exogenous factors. Because patients with hemolytic disorders characterized with fluctuations in iron concentration demonstrate defective elastic fibers, we speculated that iron might also modulate elastogenesis. In the present report we demonstrate that treatment of cultured human skin fibroblasts with low concentration of iron 2-20 µM (ferric ammonium citrate) induced a significant increase in the synthesis of tropoelastin and deposition of insoluble elastin. Northern blot and real-time reverse transcription-PCR analysis revealed that treatment with 20 µM iron led to an increase of 3-fold in elastin mRNA levels. Because treatment with an intracellular iron chelator, desferrioxamine, caused a significant decrease in elastin mRNA level and consequent inhibition of elastin deposition, we conclude that iron facilitates elastin gene expression. Our experimental evidence also demonstrates the existence of an opposite effect, in which higher, but not cytotoxic concentrations of iron (100-400 µM) induced the production of intracellular reactive oxygen species that coincided with a significant decrease in elastin message stability and the disappearance of iron-dependent stimulatory effect on elastogenesis. This stimulatory elastogenic effect was reversed, however, in cultures simultaneously treated with high iron concentration (200 µM) and the intracellular hydroxyl radical scavenger, dimethylthiourea. Thus, presented data, for the first time, demonstrate the existence of two opposite iron-dependent mechanisms that may affect the steady state of elastin message. We speculate that extreme fluctuations in intracellular iron levels result in impaired elastic fiber production as observed in hemolytic diseases.

Full article: http://journal.9med....e.php?id=416172