elastin and Vitamin-A-Deficiency

Within the last several years, research scientists and clinicians have been intrigued with the potential use of an active form of vitamin A, retinoic acid (RA), for the treatment and prevention of emphysema. The interest in this area can be largely attributed to the work of Massaro and Massaro (1996, 1997, 2000) in which they presented evidence that RA partially protects against and to some degree restores elastase-induced emphysema in rats. The mechanism for this protective effect of RA is in part related to elastin metabolism. RA also inhibits inflammation, an upstream event that may lead to the development of emphysema. Although there is evidence of this protective effect in young rats and a mechanistic explanation, more studies are needed in humans in order to establish a role for vitamin A in protecting against emphysema. Too many unanswered questions remain to definitively state that vitamin A protects against this disease in humans. Nevertheless, the potential for this novel approach in prevention and treatment of emphysema is an exciting area of research.

Topics: Animals; Elastin; Humans; Inflammation; Lung; Pulmonary Emphysema; Smoking; Tretinoin; Vitamin A; Vitamin A Deficiency; Vitamins

Mild or marginal vitamin A deficiency (MVAD) is still a serious and widespread public health problem in pregnant women and children in developing countries. This study investigated rat lung maturation from prenatal to adult stage during pregnancy and postnatal MVAD and the recovery after postnatal vitamin A supplementation (VAS). Adult female rats and their offspring were randomized into three groups. 1.. the mothers and offspring received a normal diet.2. MVAD: The mothers and offspring received a MVAD diet.3. VAS: the mothers received MVAD diet till parturition, and then received the normal diet. The offspring of the VAS group were given low-dose vitamin A from postnatal day 1 to day 7 and received the normal diet after weaning. The lung development, structure, and collagen and elastic fiber of offspring were monitored by morphometric analysis at age 1 d, 2 and 8 wk, respectively. Lower body weight, lung weight, reduced numbers of alveoli and total alveolar surface area as well as increased alveoli septa thickness was observed in MVAD compared to that in the control animals. Increased collagen deposits and decreasing elastic fiber were found in MVAD rats. However, all of these were significantly improved in VAS-treated animals. These data suggest that the rat lung is sensitive to MVAD during the developing stage. Early postnatal vitamin A supplementation can partially restore the normal lung structure.

Topics: Animals; Animals, Newborn; Body Weight; Collagen; Diet; Elastin; Female; Fetal Nutrition Disorders; Lung; Organ Size; Pregnancy; Pregnancy Complications; Rats; Rats, Wistar; Vitamin A; Vitamin A Deficiency

The mechanical properties of the pulmonary parenchyma are strongly influenced by the collagen and elastic fibers that course through the alveolar interstitium and interconnect the bronchovascular bundles. Vitamin A deficiency (VAD) produces effacement and remodeling of the alveolar architecture, resulting in alternating areas of alveolar dilatation and collapse. To better understand the mechanical consequences and reversibility of this remodeling process, we have examined how the remodeling of collagen and elastic fibers correlates with the mechanical properties of the lung parenchyma in VAD rats. An oscillatory impulse was applied at different levels of stress on the fiber network and the tissue damping (G), elastance (H), hysteresivity (G/H, eta) were analyzed. At a supra-physiological functional residual capacity, the lung parenchyma of VAD rats exhibited a lower G and H than Vitamin A sufficient (VAS) rats, which was accompanied by a significant decrease in the quantity of parenchymal collagen and collagen fibers. Retinoic acid (RA) administration restored the parenchymal collagen and mechanical properties.

Topics: Air Pressure; Animals; Collagen; Elasticity; Elastin; Female; Lung; Lung Volume Measurements; Microscopy, Electron, Scanning; Muscle Rigidity; Positive-Pressure Respiration; Pulmonary Alveoli; Pulmonary Atelectasis; Rats; Rats, Inbred Lew; Respiration, Artificial; Respiratory Mechanics; Thoracic Wall; Vitamin A Deficiency

Bronchial hyperreactivity is influenced by properties of the conducting airways and the surrounding pulmonary parenchyma, which is tethered to the conducting airways. Vitamin A deficiency (VAD) is associated with an increase in airway hyperreactivity in rats and a decrease in the volume density of alveoli and alveolar ducts. To better define the effects of VAD on the mechanical properties of the pulmonary parenchyma, we have studied the elastic modulus, elastic fibers and elastin gene-expression in rats with VAD, which were supplemented with retinoic acid (RA) or remained unsupplemented.. Parenchymal mechanics were assessed before and after the administration of carbamylcholine (CCh) by determining the bulk and shear moduli of lungs that that had been removed from rats which were vitamin A deficient or received a control diet. Elastin mRNA and insoluble elastin were quantified and elastic fibers were enumerated using morphometric methods. Additional morphometric studies were performed to assess airway contraction and alveolar distortion.. VAD produced an approximately 2-fold augmentation in the CCh-mediated increase of the bulk modulus and a significant dampening of the increase in shear modulus after CCh, compared to vitamin A sufficient (VAS) rats. RA-supplementation for up to 21 days did not reverse the effects of VAD on the elastic modulus. VAD was also associated with a decrease in the concentration of parenchymal elastic fibers, which was restored and was accompanied by an increase in tropoelastin mRNA after 12 days of RA-treatment. Lung elastin, which was resistant to 0.1 N NaOH at 98 degrees, decreased in VAD and was not restored after 21 days of RA-treatment.. Alterations in parenchymal mechanics and structure contribute to bronchial hyperreactivity in VAD but they are not reversed by RA-treatment, in contrast to the VAD-related alterations in the airways.

Topics: Adaptation, Physiological; Animals; Elasticity; Elastin; Female; Gene Expression Regulation; Lung; Rats; Rats, Inbred Lew; Tretinoin; Vitamin A Deficiency

Vitamin A is required during pregnancy for fetal lung development. These experiments monitored fetal lung morphology in normal and vitamin A-deficient rats. The expression of elastin and the growth arrest-specific gene 6 (gas6) in fetal and neonatal hearts and lungs was assessed by Northern blotting. In normal-fed rats, elastin and gas6 were expressed in the fetal lung and heart from day 19 of gestation up to day 2 postnatally. Maternal vitamin A deficiency altered fetal lung development. On day 20, the bronchial passageways were less developed and showed reduced staining for elastic fibers, and in the neonates, the relative air space and the size of the sacculi were reduced. In the fetal lung, the mRNAs for elastin and gas6 were reduced to 56 and 68% of the control values, respectively. In the fetal heart, the mRNA for elastin was reduced to 64% of the control value, whereas gas6 was increased twofold. In the neonate, there was no change in elastin expression in the lung or heart, but gas6 expression in the heart was increased twofold. These results suggest that, in the pregnant rat, vitamin A deficiency may retard fetal lung development or influence the differentiation of critical cell lines. The changes in elastin and gas6 expression may be used to identify the cell types affected.

Topics: Animals; Elastin; Female; Fetal Heart; Fetus; Gene Expression Regulation, Developmental; Intercellular Signaling Peptides and Proteins; Lung; Maternal-Fetal Exchange; Pregnancy; Pregnancy, Animal; Proteins; Rats; Rats, Inbred Strains; RNA, Messenger; Vitamin A; Vitamin A Deficiency

Topics: Animals; Aorta; Elastic Tissue; Elasticity; Elastin; Lung; Lung Compliance; Rabbits; Vitamin A Deficiency