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Aortic features in Tangier disease and pathogenetic considerations--Part I. Fatty dots and streaks
1Department of Pathology, University of Western Ontario, London, Canada.
Abstract:
Morphological studies of aortic fatty dots and streaks, and the adjacent normally appearing intima, in a 5 3/4-year-old boy who died of pneumonia, showed several hitherto unreported features. In lesions, lipid vacuoles and/or other cytoplasmic "inclusions" (ultrastructurally considered to present complex forms of lipids) were present on occasion in the endothelium but consistently involved the (intimal) smooth muscle cells (SMC). Similar changes were present in the adjacent intima, but were here less prominent and "tapered off" distally. A moderate number of macrophages also contained cytoplasmic lipids but such cells entirely free of lipid inclusions were observed, too. Most surprisingly, dilated and many cisternae of rough-surfaced endoplasmic reticulum (ER) in the SMC of lesions were associated spatially with cytoplasmic droplets and other forms of lipids. The results of these studies question the generally accepted central role of macrophages as being primarily involved in the pathogenesis of tissue changes in Tangier disease. It is possible that in view of the absence or paucity of high-density lipoproteins (HDL) and alterations of (their) apo A-I and apo A-II (as well as of other lipids), the arterial SMC may be in some way involved in the metabolism of the above substances in this disorder. Support of this tentative (and highly speculative) assumption must await further work utilizing tissues and cells other than those containing macrophages and other derivatives of reticulo-endothelial system.
Insights
Smooth muscle cells in aortic lesions show lipid accumulation and endoplasmic reticulum changes, challenging the role of macrophages in Tangier disease pathogenesis. Arterial smooth muscle cells may play a role in lipid metabolism.
Area of Science:
- Cardiovascular pathology
- Cell biology
- Lipid metabolism
Background:
- Tangier disease is characterized by lipid metabolism defects, primarily affecting high-density lipoproteins (HDL).
- Macrophages are traditionally considered central to the pathogenesis of lipid deposition in Tangier disease.
Observation:
- Morphological study of aortic fatty streaks in a pediatric case revealed lipid vacuoles within endothelial cells and smooth muscle cells (SMC).
- Lipid inclusions were consistently observed in intimal SMC, with similar but less prominent changes in adjacent intima.
- Macrophages contained lipids, but lipid-free macrophages were also present, alongside SMC exhibiting dilated rough endoplasmic reticulum associated with lipid droplets.
Findings:
- Smooth muscle cells (SMC), not just macrophages, accumulate lipids in aortic lesions.
- Abnormalities in the rough endoplasmic reticulum of SMC are spatially linked to lipid accumulation.
- These findings challenge the established view of macrophages as the sole primary mediators of lipid deposition in Tangier disease.
Implications:
- Arterial SMC may be involved in the metabolism of lipids, including high-density lipoproteins (HDL) and their apolipoproteins (apo A-I, apo A-II), in Tangier disease.
- Further research is needed to elucidate the specific role of SMC in this disorder, moving beyond macrophage-centric models.
- This study opens new avenues for understanding the cellular mechanisms underlying lipid disorders affecting the vasculature.