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.
This study aimed to do a brief review of enzootic calcinosis in sheep and to report two outbreaks of Nierembergia rivularis poisoning in sheep in Uruguay. The outbreaks occurred in farms located on an island (Outbreak A) and on the border (Outbreak B) of the Rincón del Bonete lake. Sheep of all ages were affected, with the exception of suckling lambs. The first clinical signs occurred in early October, and deaths occurred from December to February. Outbreaks A and B had morbidity of 10%, and the mortality was 7.2% and 2.8% in Outbreaks A and B, respectively. The clinical signs included weight loss, retracted abdomen, stiff gait, and kyphosis. An autopsy was performed on one sheep from each outbreak. Pulmonary and arterial calcification, nephrocalcinosis, and osteopetrosis were observed in gross and microscopic examination in both sheep. Thyroid C-cell hyperplasia and carcinoma was observed in sheep A. Sheep B showed thyroid C-cell hyperplasia and parathyroid chief cell atrophy. The parathyroid was not examined in the sheep from Outbreak A. The differential diagnosis of enzootic calcinosis in southern South America should consider four toxic plants in the Solanaceae family: Solanum glaucophyllum, Solanum stuckertii, Nierembergia veitchii, and Nierembergia rivularis.
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