title: Bone morphogenic protein-4 expression in vascular lesions of calciphylaxis.
abstract: Calciphylaxis is characterized by an extensive media-calcification of cutaneous and subcutaneous arterioles and capillaries. Recent studies have provided evidence that vascular calcification is a process with similarities to bone metabolism. Bone morphogenic protein-4 (BMP-4) is physiologically involved in bone development and repair. The presence of BMP-4 in atherosclerosis and in sclerotic heart valves led us to suggest that BMP-4 is also involved in calciphylaxis. A 47-year-old male patient developed end-stage renal failure due to chronic glomerulonephritis. He has had two kidney transplants with an immunosuppressive regimen consisting of cyclosporine A and steroids. He was admitted to our hospital because of an increase in serum creatinine (Cr) and he subsequently developed progressive dermal ulcerations. A skin biopsy led to the diagnosis of calciphylaxis. Immunohistochemistry for BMP-4 of a skin specimen from our patient showed strong cytoplasmic immunoreactivity of intradermal cells with clear spatial association to arterioles and hair follicles. Whereas there are identified inhibitors and promoters of vascular calcification, the presence of BMP-4 has not been demonstrated in calcific uremic arteriolopathy. In contrast to atherosclerosis, BMP-4 in calciphylaxis cannot be found in vascular media, but in intradermal cells at the border of arterioles and hair follicles. Therefore, in calciphylaxis BMP-4 can play the role of a cytokine, a growth factor or a media-calcification promoter.
authors.affiliation: Department of Nephrology and Medical Intensive Care, Medical Faculty of the Charité, Humboldt University, Berlin, Germany. wanja.griethe@charite.de
authors.forename: Wanja
authors.initials: W
authors.lastname: Griethe
authors.forename: Roland
authors.initials: R
authors.lastname: Schmitt
authors.forename: Jan Steffen
authors.initials: JS
authors.lastname: Jurgensen
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bachmann
authors.forename: Kai-Uwe
authors.initials: KU
authors.lastname: Eckardt
authors.forename: Ralf
authors.initials: R
authors.lastname: Schindler
mesh_terms: D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002115:Calciphylaxis / Q000378:metabolism* / Q000473:pathology; D003404:Creatinine / Q000097:blood; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D012867:Skin / Q000098:blood supply / Q000473:pathology; D017445:Skin Diseases, Vascular / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D014511:Uremia / Q000150:complications / Q000378:metabolism; D014652:Vascular Diseases / Q000209:etiology / Q000378:metabolism
chemical_list: C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D003404:Creatinine