Abstract 304: Global Transcriptional Effects of Vitamin A Deficiency on the Postnatal Heart

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Cristi L Galindo ◽  
Truc-Linh Tran ◽  
Xuyang Peng ◽  
Douglas B Sawyer ◽  
Mary Asson-Batres

Vitamin A (VA) is the chemical precursor of retinoic acid (RA), which is critical for embryonic development and for growth, immunity, metabolism, and cell differentiation in postnatal regenerating systems such as skin, sensory organs, and stem cell niches in the brain. VA is also essential for embryonic heart development, and we hypothesized that Vitamin A might exert an effect on the postnatal heart similar to what is observed for other tissues. Here, we report the global transcriptional profiles of wild-type (WT) mice fed a VA sufficient diet (VAS) compared with retinyl acyl transferase (LRAT) knock-out mice fed either a VAS or VA deficient (VAD) diet. Knockout of the LRAT gene alone was sufficient to induce differential expression of 576 genes relative to WT. Feeding LRAT mutant mice a VAD diet resulted in a change in the relative expression levels of 257 genes relative to LRAT mutant mice fed a VAS diet. As expected, we observed transcriptional alterations related to Vitamin A metabolism, including an increase in the gene encoding cellular retinoid binding protein 7 and down-regulation of the retinol metabolic enzymes Cy1a2 and Cyp2a4. Importantly, several cardiac genes not previously known to require VA were perturbed, including the gene encoding B-type natriuretic peptide, which was down-regulated in mutant mice irrespective of diet, and A-type natriuretic peptide, which was decreased only in mice fed the VAD diet. There was also a striking effect of VAD on genes important for immune responses, which could have an impact on the wound healing process subsequent to injury of the heart. This is consistent with recent evidence that showed that Vitamin A deficiency influences post-infarct ventricular remodeling in rats. In summary, this is the first microarray study of Vitamin A deficiency in the postnatal heart, which suggests mechanisms by which Vitamin A depletion may alter myocardial maintenance and repair after injury.

Development ◽  
1997 ◽  
Vol 124 (23) ◽  
pp. 4749-4758 ◽  
Author(s):  
P. Kastner ◽  
N. Messaddeq ◽  
M. Mark ◽  
O. Wendling ◽  
J.M. Grondona ◽  
...  

Knock-out of the mouse RXRalpha gene was previously shown to result in a hypoplastic heart ventricular wall, histologically detectable in 12.5 dpc fetuses. We show here that a precocious differentiation can be detected as early as 8.5 dpc in ventricular cardiomyocytes of RXRalpha(−/−) mutants. This precocious differentiation, which is characterized by the presence of striated myofibrils, sarcoplasmic reticulum and intercalated disks, is found after 9.5 dpc in about 50% of RXRalpha(−/−) subepicardial myocytes. In contrast, wild-type subepicardial myocytes remain morphologically undifferentiated up to at least 16.5 dpc. A similar precocious differentiation was observed in 9.5 dpc subepicardial myocytes of several RXRbeta(−/−) and RARalpha(−/−) mutants, as well as in vitamin A-deficient embryos. The proportion of differentiated subepicardial myocytes almost reached 100% in RXRalpha/RXRbeta double null mutants, indicating a partial functional redundancy between RXRalpha and RXRbeta. This differentiation defect was always paralleled by a decrease in the mitotic index. In addition, subepicardial myocytes of RXRalpha(−/−), RXRalpha(−/−)/RXRbeta(−/−) or vitamin A deficient, but not of RXRbeta(−/−) and RARalpha(−/−) embryos, were often flattened and more loosely connected to one another than those of WT embryos. Thus, retinoids are required at early stages of cardiac development to prevent differentiation, support cell proliferation and control the shape of ventricular myocytes, and both RXRs and RARs participate in the mediation of these functions.


Endocrinology ◽  
2003 ◽  
Vol 144 (1) ◽  
pp. 240-246 ◽  
Author(s):  
Sarah E. Abbey ◽  
Lincoln R. Potter

Abstract C-type natriuretic peptide (CNP), found in endothelial cells, chondrocytes, and neurons, binds its cognate transmembrane receptor, natriuretic peptide receptor-B (NPR-B/GC-B), and stimulates the synthesis of the intracellular signaling molecule, cGMP. The known physiologic consequences of this binding event are vasorelaxation, inhibition of cell proliferation, and the stimulation of long bone growth. Here we report that 10% fetal bovine serum markedly reduced CNP-dependent cGMP elevations in NIH3T3 fibroblast. The purified serum components platelet-derived growth factor and lysophosphatidic acid (LPA) mimicked the effect of serum on CNP-dependent cGMP elevations, but the latter factor resulted in the most dramatic reductions. The LPA-dependent inhibition was rapid and dose dependent, having t1/2 and IC50 values of approximately 5 min and 3.0 μm LPA, respectively. The decreased cGMP concentrations resulted from reduced CNP-dependent NPR-B guanylyl cyclase activity that did not require losses in receptor protein or activation of protein kinase C, indicating a previously undescribed desensitization pathway. These data suggest that NPR-B is repressed by LPA and that one mechanism by which LPA exerts its effects is through the heterologous desensitization of the CNP/NPR-B/cGMP pathway. We hypothesize that cross-talk between the LPA and CNP signaling pathway maximizes the response of fibroblasts in the wound-healing process.


Development ◽  
1996 ◽  
Vol 122 (7) ◽  
pp. 2173-2188 ◽  
Author(s):  
J.M. Grondona ◽  
P. Kastner ◽  
A. Gansmuller ◽  
D. Decimo ◽  
P. Chambon ◽  
...  

The eye is the organ whose development is the most frequently altered in response to maternal vitamin A deficiency [VAD; Warkany, J. and Schraffenberger, S. (1946). Archs Ophthalmol. 35, 150–169]. With the exception of prenatal retinal dysplasia, all the ocular abnormalities of the fetal VAD syndrome are recapitulated in mouse mutants lacking either RARalpha and RARbeta2, RARalpha and RARgamma, RARgamma and RARbeta2, or RXRalpha [Lohnes, D., Mark, M., Mendelsohn, C., Dolle, P., Dierich, A., Gorry, P., Gansmuller, A. and Chambon, P. (1994) Development 120, 2723–2748; Mendelsohn, C., Lohnes, D., Decimo, D., Lufkin, T., LeMeur, M., Chambon, P. and Mark, M. (1994) Development 120, 2749–2771; Kastner, P., Grondona, J. Mark, M., Gansmuller, A., LeMeur, M., Decimo, D., Vonesch, J.L., Dolle, P. and Chambon, P. (1994) Cell 78, 987–1003], thus demonstrating that retinoic acid (RA) is the active vitamin A metabolite during prenatal eye morphogenesis. Whether retinoids are also involved in postnatal eye development could not be investigated, as VAD newborns are not viable and the above RAR double null mutants and RXRalpha null mutants died in utero or at birth. We report here the generation of viable RARbeta2/RARgamma2 double null mutant mice, which exhibit several eye defects. The neural retina of newborn RARbeta2gamma2 mutants is thinner than normal due to a reduced rate of cell proliferation, and from day 4 shows multiple foci of disorganization of its layers. These RARbeta2gamma2 mutants represent the first genetically characterized model of retinal dysplasia and their phenotype demonstrates that RARs, and therefore RA, are required for retinal histogenesis. The RARbeta2gamma2 retinal pigment epithelium (RPE) cells display histological and/or ultrastructural alterations and/or fail to express cellular retinol binding protein I (CRBPI). Taken altogether, the early onset of the RPE histological defects and their striking colocalisation with areas of the neural retina displaying a faulty laminar organization, a reduced neuroblastic proliferation, and a lack of photoreceptor differentiation and/or increased apoptosis, make the RPE a likely target tissue of the RARbeta2gamma2 double null mutation. A degeneration of the adult neural retina, which may similarly be secondary to a defective RPE, is also observed in these mutants, thus demonstrating an essential role of RA in the survival of retinal cells. Moreover, all RARbeta2gamma2 mutants display defects in structures derived from the periocular mesenchyme including local agenesis of the choroid and of the sclera, small eyelids, and a persistence of the primary mesenchymal vitreous body. A majority of the RARbeta2 single null mutants also exhibit this latter defect, thus demonstrating that the RARbeta2 isoform plays a unique role in the formation of the definitive vitreous body.


2010 ◽  
Vol 26 (3) ◽  
pp. 395-402 ◽  
Author(s):  
Paula S. Azevedo ◽  
Marcos F. Minicucci ◽  
Fernanda Chiuso-Minicucci ◽  
Luis A. Justulin Jr ◽  
Luiz S. Matsubara ◽  
...  

2019 ◽  
Vol 28 (10) ◽  
pp. 683-693 ◽  
Author(s):  
Beniamino Palmieri ◽  
Maria Vadalà ◽  
Carmen Laurino

Nutrition can be outlined in terms of epigenetic signals influencing each of the wound healing steps (haemostasis, inflammatory, proliferative and remodelling phase). Specific nutrients, such as amino acids, minerals, vitamins, natural compounds and herbal extracts, target DNA-regulating transcription factors, cytokines, extracellular matrix proteins and glycosaminoglycan, and are specifically involved in the wound healing process. This review focuses on experimental in vivo and clinical evidence of dietary supplements administration in pressure ulcers. A good nutritional status is, for example, fundamental to the haemostasis phase of skin wounds. In the inflammatory phase, vitamin A enhances cytokine release, bromelain and amino acids prevent prolonged inflammatory events, while vitamin C enhances neutrophil migration and lymphocyte activation. In the proliferative phase, vitamin C and Centella asiatica are required for collagen synthesis. Glucosamine enhances hyaluronic acid production, vitamin A promotes epithelial cell differentiation, zinc is required for DNA and protein synthesis and cell division, and Aloe vera supports granulation tissue generation. Finally, in the remodelling phase, amino acids and proteins play a key role in wound scar stabilisation.


2013 ◽  
Vol 83 (2) ◽  
pp. 122-128 ◽  
Author(s):  
Cécile Renaud ◽  
Jacques Berger ◽  
Arnaud Laillou ◽  
Sylvie Avallone

Vitamin A deficiency is still one of the major public health problems in least developed countries. Fortification of vegetable oils is a strategy implemented worldwide to prevent this deficiency. For a fortification program to be effective, regular monitoring is necessary to control food quality in the producing units. The reference methods for vitamin A quantification are expensive and time-consuming. A rapid method should be useful for regular assessment of vitamin A in the oil industry. A portable device was compared to high-performance liquid chromatography (HPLC) for three plant oils (rapeseed, groundnut, and soya). The device presented a good linearity from 3 to 30 mg retinol equivalents per kg (mg RE.kg- 1). Its limits of detection and quantification were 3 mg RE.kg- 1 for groundnut and rapeseed oils and 4 mg RE.kg- 1 for soya oil. The intra-assay precision ranged from 1.48 % to 3.98 %, considered satisfactory. Accuracy estimated by the root mean squares error ranged from 3.99 to 5.49 and revealed a lower precision than HPLC (0.4 to 2.25). Although it offers less precision than HPLC, the device estimates quickly the vitamin A content of the tested oils from 3 or 4 to 15 mg RE.kg- 1.


2014 ◽  
Vol 84 (Supplement 1) ◽  
pp. 52-59 ◽  
Author(s):  
Sherry A. Tanumihardjo ◽  
Anura V. Kurpad ◽  
Janet R. Hunt

The current use of serum retinol concentrations as a measurement of subclinical vitamin A deficiency is unsatisfactory for many reasons. The best technique available for vitamin A status assessment in humans is the measurement of total body pool size. Pool size is measured by the administration of retinol labelled with stable isotopes of carbon or hydrogen that are safe for human subjects, with subsequent measurement of the dilution of the labelled retinol within the body pool. However, the isotope techniques are time-consuming, technically challenging, and relatively expensive. There is also a need to assess different types of tracers and doses, and to establish clear guidelines for the use and interpretation of this method in different populations. Field-friendly improvements are desirable to encourage the application of this technique in developing countries where the need is greatest for monitoring the risk of vitamin A deficiency, the effectiveness of public health interventions, and the potential of hypervitaminosis due to combined supplement and fortification programs. These techniques should be applied to validate other less technical methods of assessing vitamin A deficiency. Another area of public health relevance for this technique is to understand the bioconversion of β-carotene to vitamin A, and its relation to existing vitamin A status, for future dietary diversification programs.


2020 ◽  
Author(s):  
M Nagel ◽  
C Labenz ◽  
M Nguyen-Tat ◽  
N Cabezas Wallscheid ◽  
C Czauderna ◽  
...  

2015 ◽  
Vol 18 (3) ◽  
pp. 109
Author(s):  
Huseyin Saskin ◽  
Mustafa Idiz ◽  
Cagri Duzyol ◽  
Huseyin Macika ◽  
Rezan Aksoy

Pulmonary agenesis is associated with the absence of pulmonary vessels, bronchi, or parenchyma. This condition usually occurs between the 4th and 5th week of gestation during the embryonic phase. Etiopathogenic factors associated with pulmonary agenesis are not fully understood. In the literature, genetic and teratogenic factors, viral infections, and vitamin-A deficiency are shown to be associated with pulmonary agenesis [Malcon 2012]. This condition may be seen unilaterally or bilaterally. Although the precise rate of incidence is unknown, it is estimated to occur in one of every 10,000 to 12,000 live births [Yetim 2011]. There is a 1.3:1 female predominance with unilateral agenesis [Halilbasic 2013]


2019 ◽  
Vol 2 (1) ◽  
pp. 14-17
Author(s):  
Nurul Aini Siagian ◽  
Syafira Nusaibah ◽  
Andayani Boang Manalu

Early mobilization includes factors that can affect the process of wound healing after surgery. Immediate mobilization in stages is very useful for the process of healing wounds and preventing infection and venous thrombosis. The purpose of this study was to determine whether there is a relationship between early mobilization and the process of healing wound post operative sectio caesarea at Sinar Husni General Hospital Medan Helvetia. The research design used was analytic survey with cross sectional approach. The sample in this study used the Consecutive Sampling method of data collection using a checklist sheet conducted on a sample of 19 respondents. The results of the study in this study are the majority of respondents who did early mobilization and who experienced rapid wound healing process as many as 4 people (21%) while the minority of respondents who did early mobilization and who experienced slow wound healing process were 1 person (5.3%). The majority of respondents who did not mobilize early and who experienced a slow wound healing process were 11 people (57.9%) and a minority who did not mobilize early and who experienced rapid healing as many as 4 people (21.1%). Statistical test results obtained p value = 0.046 <0.005. The conclusions of the results of this study indicate there is a relationship between early mobilization and the process of healing post operative sectio of caesarea. Suggestions The results of this study can be applied as a reference to improve nursing care services, especially in providing counseling and assistance to patients.


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