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  • Oldenburg, JoppeUppsala universitet,Institutionen för immunologi, genetik och patologi (author)

Propranolol Reduces the Development of Lesions and Rescues Barrier Function in Cerebral Cavernous Malformations : A Preclinical Study

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • Lippincott Williams & Wilkins,2021
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-442603
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-442603URI
  • https://doi.org/10.1161/STROKEAHA.120.029676DOI
  • https://res.slu.se/id/publ/110766URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Background and Purpose: Cerebral cavernous malformations (CCM) present as mulberry-like malformations of the microvasculature of the central nervous system. Current medical treatment of CCM lesions is limited to surgical removal of the vascular malformations. It is, therefore, important to identify therapeutic drug treatments for patients with CCM. Propranolol has shown great benefit in the treatment of infantile hemangioma. In addition, patients with CCM who receive propranolol have demonstrated a reduction of their lesions. Our investigation set out to provide preclinical data to support propranolol as a therapeutic treatment.Methods: An inducible endothelial-specific Ccm3 knockout murine model (CCM3(iECKO)) was used, with assessment of lesion quantity and size following oral treatment with propranolol. Scanning and transmission electron microscopy were used to characterize the CCM3(iECKO) lesions and the effects of propranolol on the disease. Immunofluorescent imaging was used to investigate pericyte coverage in the propranolol-treated CCM3(iECKO) mice.Results: With propranolol treatment, the lesion quantity, size, and volume decreased in both the brain and retina in the CCM3(iECKO) model. Novel characteristics of the CCM3(iECKO) lesions were discovered using electron microscopy, including plasmalemmal pits and thickening of the endothelial-pericyte basal membrane. These characteristics were absent with propranolol treatment. Pericyte coverage of the CCM3(iECKO) lesions increased after propranolol treatment, and vascular leakage was reduced.Conclusions: This study supports the concept that propranolol can be used to reduce and stabilize vascular lesions and can, therefore, be suggested as a pharmaceutical treatment for CCM.

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  • Malinverno, MatteoFIRC Inst Mol Oncol Fdn, Vasc Biol Unit, Milan, Italy. (author)
  • Globisch, Maria A.Uppsala universitet,Vaskulärbiologi(Swepub:uu)margl506 (author)
  • Maderna, ClaudioFIRC Inst Mol Oncol Fdn, Vasc Biol Unit, Milan, Italy. (author)
  • Corada, MonicaFIRC Inst Mol Oncol Fdn, Vasc Biol Unit, Milan, Italy. (author)
  • Orsenigo, FabrizioFIRC Inst Mol Oncol Fdn, Vasc Biol Unit, Milan, Italy. (author)
  • Conze, Lei LiuUppsala universitet,Vaskulärbiologi(Swepub:uu)leliu102 (author)
  • Rorsman, CharlotteUppsala universitet,Vaskulärbiologi(Swepub:uu)charrors (author)
  • Sundell, VeronicaUppsala universitet,Institutionen för immunologi, genetik och patologi (author)
  • Arce, MaximilianoUppsala universitet,Vaskulärbiologi(Swepub:uu)maxar829 (author)
  • Smith, Ross O.Uppsala universitet,Vaskulärbiologi(Swepub:uu)rossm781 (author)
  • Yau, Anthony C. Y.Uppsala universitet,Vaskulärbiologi(Swepub:uu)antya284 (author)
  • Hulsart Billström, Gry,1982-Uppsala universitet,Ortopedi(Swepub:uu)gryhu107 (author)
  • Öhman, CarolineUppsala universitet,Tillämpad materialvetenskap(Swepub:uu)caroh395 (author)
  • Beznoussenko, Galina, VFIRC Inst Mol Oncol Fdn, Vasc Biol Unit, Milan, Italy.;FIRC Inst Mol Oncol Fdn, Elect Microscop Lab, Milan, Italy. (author)
  • Mironov, Alexander A.FIRC Inst Mol Oncol Fdn, Elect Microscop Lab, Milan, Italy. (author)
  • Fernando, DineshSwedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Skogens biomaterial och teknologi,Department of Forest Biomaterials and Technology,Swedish Univ Agr Sci, Dept Biomat & Technol Wood Sci, Uppsala, Sweden.(Swepub:slu)50319 (author)
  • Daniel, GeoffreySwedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Skogens biomaterial och teknologi,Department of Forest Biomaterials and Technology,Swedish Univ Agr Sci, Dept Biomat & Technol Wood Sci, Uppsala, Sweden.(Swepub:slu)47230 (author)
  • Olivari, DavideInst Ric Farmacol Mario Negri IRCCS, Cardiopulm Physiopathol Lab, Cardiovasc Med Dept, Milan, Italy. (author)
  • Fumagalli, FrancescaInst Ric Farmacol Mario Negri IRCCS, Cardiopulm Physiopathol Lab, Cardiovasc Med Dept, Milan, Italy. (author)
  • Lampugnani, Maria GraziaFIRC Inst Mol Oncol Fdn, Vasc Biol Unit, Milan, Italy.;Mario Negri Inst Pharmacol Res, Milan, Italy. (author)
  • Dejana, ElisabettaUppsala universitet,Vaskulärbiologi,FIRC Inst Mol Oncol Fdn, Vasc Biol Unit, Milan, Italy.;Univ Milan, Sch Med, Dept Oncol & Haematooncol, Milan, Italy.(Swepub:uu)elide443 (author)
  • Magnusson, PeetraUppsala universitet,Vaskulärbiologi(Swepub:uu)petrmagn (author)
  • Uppsala universitetInstitutionen för immunologi, genetik och patologi (creator_code:org_t)
  • Sveriges lantbruksuniversitet

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