03391nam a2200313 a 450000100080000000500110000800800410001902200140006002400350007410000160010924501470012526001200027250006790039252017160107165300280278765300130281565300240282865300130285265300170286565300310288265300130291365300330292670000170295970000180297670000260299470000190302070000200303970000180305910632332022-11-30       2022    bl uuuu     u01u1 u    #d  a0300-98587 a10.1177/030098582210984302DOI1 aMACHADO, M.  aPoisoning by Nierembergia veitchiibEffects on vascular smooth muscle cells in the pathogenesis of enzootic calcinosis.h[electronic resource]  aVeterinary Pathology, 2022, Volume 59, Issue 5, pages 814-823. doi: https://doi.org/10.1177/03009858221098430c1177  aArticle history: Article first published online May 19, 2022; Published online September 2022. -- Corresponding Author: Franklin Riet-Correa, Postgraduate Program in Animal Science in the Tropics, School of Veterinary Medicine and Animal Science, Federal University of Bahia, Salvador, Bahia 40170-110, Brazil. Email: franklinrietcorrea@gmail.com  --  This work was funded by National Institute of Agricultural Research (INIA) of Uruguay (Project CL 44), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil, (Finance Code 001) and National University of La Plata (Project V270). A postgraduate scholarship was provided to Mizael Machado by INIA, Uruguay.  aABSTRACT - Vascular mineralization is a hallmark of enzootic calcinosis. Histopathological, ultrastructural, and immunohistochemical investigations were performed on the external carotid arteries of seven sheep naturally poisoned by Nierembergia veitchii. Histologically, moderate to marked hyperplasia of the tunica intima was observed without mineralization. The tunica media exhibited mild to severe mineralization and osteochondroid metaplasia. Sheep with enzootic calcinosis showed arterial overexpression of osteopontin and tissue-nonspecific alkaline phosphatase and immunolabeling for osteonectin and osteocalcin in both intima and media layers of the tested arteries. The main ultrastructural finding in the tunica media was a marked phenotypic change of vascular smooth muscle cells from a contractile phenotype (VSMC-C) into a synthetic phenotype (VSMC-S). In the tunica media, VSMC-S produced matrix and extracellular vesicles, forming mineralizable granules associated with arterial mineralization. VSMC-S were also present in the tunica intima, but matrix and extracellular vesicles and mineralization were not observed. The absence of matrix and extracellular vesicles in the intimal hyperplasia, even in the presence of noncollagenous bone proteins, tissue-nonspecific alkaline phosphatase, and vitamin D receptors, reinforces the hypothesis that the presence of matrix and extracellular vesicles are crucial for the development of vascular mineralization in enzootic calcinosis. It is proposed that the two different VSMC-S phenotypes in calcinosis are due to the expression of at least two genetically different types of these cells induced by the action of 1,25(OH)2D3. © The Author(s) 2022.  aArterial mineralization  aArteries  aEnzootic calcinosis  aExosomes  aPathogenesis  aPLATAFORMA DE SALUD ANIMAL  aToxicity  aVascular smooth muscle cells1 aCASTRO, M.B.1 aWILSON, T. M.1 aGONÇALVES , A. A. B.1 aPORTIANSKY, E.1 aRIET-CORREA, F.1 aBARROS, S. S.