Arterial diffuse intimal thickening associated with enzootic calcinosis of sheep

Abstract

Pesq. Vet. Bras. 18(1):9-15, jan./mar. 1998 9 RESUMO.-[Espessamento intimal difuso das artérias na calcinose enzoótica dos ovinos.] Foram feitos estudos morfométrico, imunoistoquímico e ultra-estrutural do espessamento intimal difuso (DIT) das artérias de 7 ovinos com sinais clínicos de calcinose enzoótica espontânea causada pela ingestão da planta Nierembergia veitchii. As lesões caracterizavam-se por deposição de sais de cálcio na média como placas e estrias que, com frequência faziam saliência para a luz, criando rugosidades e irregularidades da íntima. Não foram observadas calcificações na artéria pulmonar e no sistema venoso. Microscopicamente, as calcificações das artéri-as restringiam-se quase que exclusivamente à média. Na imunoistoquimica, foi verificada α-actina nas células da mé-dia e nas do espessamento intimal. Receptores para 1,25(OH) 2 D 3 foram evidenciados nos núcleos das células musculares da média, da íntima e das células endoteliais. As aná-lises morfométricas em microscopia ótica revelaram, nas artérias, DIT irregularmente distribuido sem relação com a intensidade dos processos de calcificação subjacente nem com a espessura da média remanescente. A morfometria das alterações ultra-estruturais das células musculares lisas da mé-dia e da íntima espessada, mostrou que nessas últimas foi verificado aumento de até 318% na fração volumétrica das organelas de síntese em detrimento dos elementos contráteis, Morphometric, immunohistochemical and ultrastructural studies were carried out on the diffuse intimal thickening (DIT) in arteries of 7 sheep with clinical signs of naturally occurring enzootic calcinosis due to ingestion of the plant Nierembergia veitchii. Arterial lesions consisted of medial deposition of calcium salts and DIT. Calcification of the intima was rare, mild and located near the elastic lamina. By immunohistochemistry α-actin was detected in cells of the media and in cells forming the intimal thickening. Receptors for 1,25(OH) 2 vitamin D 3 were detected in nuclei of intimal, medial and endothelial cells. DIT was irregularly distributed and was neither proportionally related to the intensity of the underlying mineralization area nor to the thickening of the remaining media. Ultrastructural morphometry in smooth muscle cells (SMCs) of the media and thickened intima revealed, in the latter, an increase of 318% in the volumetric fraction of those organelles involved in synthesis and a proportional decrease in contractile elements when compared to normal values of media cells. There were histological and ultrastructural evidences of modification of SMCs and their migration to the intima, where they proliferated causing DIT. It was concluded that DIT is a consistent component of arteriosclerotic lesions in N. veitchii induced calcinosis of sheep and that the predominant cell in this process is the SMCs originated from its predecessors of the media. It is suggested that the inducing factor for the arterial changes is 1,25(OH) 2 D 3 present in N. veitchii.

Macrophages and Giant Cell Proliferation Associated with Bone Protein Synthesis and Calcification in the Trachea and Bronchi of Rabbits Intoxicated with Solanum glaucophyllum

“…Such action has been suggested in similar infiltrates in the muscle layer of the stomach of rabbits experimentally poisoned with the same plant 18 and in arteries and lungs of sheep with enzootic calcinosis induced by the calcinogenic plant Nierembergia veitchii . 2, 37…”

“…5, 6, 24, 34 Receptors for 1,25(OH) 2 D 3 have been found in a variety of cells and tissues, including monocytes, macrophages, and smooth muscle cells (SMC). 33, 37…”

“…The participation of 1,25(OH) 2 D 3 in the differentiation of monocytes to macrophages and fusion to form multinucleated giant cells has been extensively studied. 1, 11, 14, 15, 21 Infiltration of macrophages and multinucleated giant cells in lung, arteries, stomach, and heart were described in natural and experimental calcinosis induced by calcinogenic plants 2– 4, 18, 28, 37, 41 that contain high levels of 1,25(OH) 2 D 3 as a glycoside derivative. 40…”

Intoxicação em ovinos por Nierembergia veitchii: observações em quatro surtos

“…O espessamento da íntima das artérias provavelmente seja o resultado da ação dessa substância sobre as células musculares lisas da média, induzindo sua diferenciação, migração para a íntima e proliferação no espaço intimal, como foi evidenciado pela reação positiva pela técnica de imunoistoquímica à α-actina de células musculares lisas (VASCONCELOS et al, 1998).…”

The quantification of vitamin D receptors in coronary arteries and their association with atherosclerosis

“…The VDR has been identified in most human tissues (including the heart, brain, kidney, and muscle [15-21]) as well as in sheep arteries (endothelium, intima, and media [22,23]). The widespread distribution of VDR implies a diverse role for the receptor, beyond regulation of phosphorus and calcium plasma concentrations [20,21].…”