Poisoning by Nierembergia veitchii: Effects on vascular smooth muscle cells in the pathogenesis of enzootic calcinosis

Abstract

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.

Plants causing poisoning outbreaks of livestock in South America: A review

“…The pathogenesis of enzootic calcinosis is complex but studies demonstrated a similarity with the bone-forming process. Recently, it was demonstrated that extracellular vesicles produced by vascular smooth muscle cells are crucial for developing vascular mineralization ( Machado et al, 2022a ).…”

Severo Sales de Barros: obituary

“…This was a study of a lifetime. In the year of his death, Severo also published a work on this subject (Machado et al 2022).…”

Severo Sales de Barros: obituário

“…Este foi o estudo de uma vida. No ano de sua morte, Severo também publicou um trabalho no assunto (Machado et al 2022).…”