26
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      A Role for PPAR β/ δ in Ocular Angiogenesis

      review-article
      1 , *
      PPAR Research
      Hindawi Publishing Corporation

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The uses of highly selective PPAR β/ δ ligands and PPAR β/ δ knockout mice have shown a direct ability of PPAR β/ δ to regulate angiogenesis in vitro and in vivo in animal models. PPAR β/ δ ligands induce the proangiogenic growth factor VEGF in many cells and tissues, though its actions in the eye are not known. However, virtually, all tissue components of the eye express PPAR β/ δ. Both angiogenesis and in particular VEGF are not only critical for the development of the retina, but they are also a central component in many common pathologies of the eye, including diabetic retinopathy and age-related macular degeneration, the most common causes of blindness in the Western world. This review, therefore, will discuss the recent evidence of PPAR β/ δ-mediated angiogenesis and VEGF release in the context of ocular disorders.

          Related collections

          Most cited references59

          • Record: found
          • Abstract: found
          • Article: not found

          Differential expression and activation of a family of murine peroxisome proliferator-activated receptors.

          To gain insight into the function of peroxisome proliferator-activated receptor (PPAR) isoforms in mammals, we have cloned and characterized two PPAR alpha-related cDNAs (designated PPAR gamma and -delta, respectively) from mouse. The three PPAR isoforms display widely divergent patterns of expression during embryogenesis and in the adult. Surprisingly, PPAR gamma and -delta are not activated by pirinixic acid (Wy 14,643), a potent peroxisome proliferator and activator of PPAR alpha. However, PPAR gamma and -delta are activated by the structurally distinct peroxisome proliferator LY-171883 and linoleic acid, respectively, indicating that each of the isoforms can act as a regulated activator of transcription. These data suggest that tissue-specific responsiveness to peroxisome proliferators, including certain fatty acids, is in part a consequence of differential expression of multiple, pharmacologically distinct PPAR isoforms.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Retinopathy of prematurity.

            Retinopathy of prematurity (ROP) is a common blinding disease in children in the developed world despite current treatment, and is becoming increasingly prevalent in the developing world. ROP progresses in two phases. The first phase begins with delayed retinal vascular growth after birth and partial regression of existing vessels, followed by a second phase of hypoxia-induced pathological vessel growth. Two major risk factors of ROP are the use of oxygen and a decreased gestation period. Excessive oxygen contributes to ROP through regulation of vascular endothelial growth factor (VEGF). Suppression of VEGF by oxygen in phase I of ROP inhibits normal vessel growth, whereas elevated levels of VEGF induced by hypoxia in phase II of ROP precipitate pathological vessel proliferation. Insulin-like growth factor 1 (IGF-1) is a critical non-oxygen-regulated factor in ROP. We have found that serum levels of IGF-1 in premature babies directly correlate with the severity of clinical ROP. IGF-1 acts indirectly as a permissive factor by allowing maximal VEGF stimulation of vessel growth. Lack of IGF-1 in preterm infants prevents normal retinal vascular growth in phase I of ROP, despite the presence of VEGF. As infants mature, rising levels of IGF-1 in phase II of ROP allows VEGF stimulated pathological neovascularization. These findings suggest that restoration of IGF-1 to normal levels might be useful in preventing ROP in preterm infants.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Transcriptional repression of atherogenic inflammation: modulation by PPARdelta.

              The formation of an atherosclerotic lesion is mediated by lipid-laden macrophages (foam cells), which also establish chronic inflammation associated with lesion progression. The peroxisome proliferator-activated receptor (PPAR) gamma promotes lipid uptake and efflux in these atherogenic cells. In contrast, we found that the closely related receptor PPARdelta controls the inflammatory status of the macrophage. Deletion of PPARdelta from foam cells increased the availability of inflammatory suppressors, which in turn reduced atherosclerotic lesion area by more than 50%. We propose an unconventional ligand-dependent transcriptional pathway in which PPARdelta controls an inflammatory switch through its association and disassociation with transcriptional repressors. PPARdelta and its ligands may thus serve as therapeutic targets to attenuate inflammation and slow the progression of atherosclerosis.
                Bookmark

                Author and article information

                Journal
                PPAR Res
                PPAR
                PPAR Research
                Hindawi Publishing Corporation
                1687-4757
                1687-4765
                2008
                11 March 2008
                : 2008
                : 825970
                Affiliations
                1Centre of Translational Medicine and Therapeutics, William Harvey Research Institute, Barts and The London, Queen Mary's School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ, UK
                a.amir@ 123456dkfz.de
                Author notes

                Recommended by R. Chuck

                Article
                10.1155/2008/825970
                2276600
                18382612
                d7c4637d-f8ef-4ac5-a870-9102a1398f70
                Copyright © 2008 David Bishop-Bailey.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 31 October 2007
                : 30 January 2008
                Categories
                Review Article

                Biochemistry
                Biochemistry

                Comments

                Comment on this article