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Experimental arteriosclerosis. I. Fibrous plaque formation in primates, an electron microscope study
Abstract:
Arteriosclerotic lesions have been produced in monkeys (Macaca nemestrina) by selective removal of the vascular endothelium with an intra-arterial balloon catheter. Immediately after de-endothelialization a platelet layer covers the denuded area. This thrombus is gradually removed and by 7 days the vessel appears to be largely reendothelialized. Beginning at day 4, smooth muscle cells undergo modification and migrate through fenestrae in the internal elastic lamina into the intima where they proliferate. By 28 days, the intimal lesion consists of multiple layers of smooth muscle cells surrounded by collagen and elastic fibers and basement-like material. After 3 months the lesions are markedly hyperplastic and contain new extracellular connective tissue elements. In contrast, with no further injury after 6 months the lesion has decreased markedly in size suggesting that it may be reversible in the absence of continued endothelial injury. The importance of endothelial "injury" exposing medial smooth muscle to plasma constituents may be the principal factors associated with the migration and proliferation of the smooth muscle cells into the intima resulting in the lesion. The smooth muscle cells do not contain lipid. The similarities of this lesion to the fibromusculo-elastic lesion or preatherosclerotic intimal hyperplasia in man makes it a useful model for the further study of atherosclerosis.
Insights
Arteriosclerotic lesions in monkeys, induced by endothelial injury, showed smooth muscle cell migration and proliferation, forming intimal lesions. These lesions may be reversible, suggesting endothelial injury is key to atherosclerosis development.
Area of Science:
- Vascular biology
- Pathology
- Atherosclerosis research
Background:
- Arteriosclerosis involves complex cellular and molecular changes in blood vessels.
- Understanding the early stages of lesion formation is crucial for developing effective treatments.
- Animal models are essential for studying the pathogenesis of vascular diseases.
Purpose of the Study:
- To investigate the development and potential reversibility of arteriosclerotic lesions in non-human primates.
- To elucidate the role of vascular endothelium injury in smooth muscle cell migration and proliferation.
- To establish a relevant animal model for studying preatherosclerotic intimal hyperplasia.
Main Methods:
- Induction of arteriosclerotic lesions in Macaca nemestrina monkeys using an intra-arterial balloon catheter to selectively remove vascular endothelium.
- Monitoring of lesion development and vascular repair over time (up to 6 months).
- Histological analysis to characterize cellular changes, extracellular matrix deposition, and lesion morphology.
Main Results:
- De-endothelialization triggered immediate platelet aggregation, followed by re-endothelialization within 7 days.
- Smooth muscle cells migrated into the intima and proliferated starting day 4, forming hyperplastic lesions by 28 days.
- Lesions showed significant regression by 6 months in the absence of continued injury, indicating potential reversibility.
Conclusions:
- Endothelial injury is a critical factor initiating smooth muscle cell migration and proliferation, leading to intimal lesion formation.
- The observed lesions closely resemble human fibromusculo-elastic lesions and preatherosclerotic intimal hyperplasia.
- This primate model provides a valuable tool for further research into atherosclerosis pathogenesis and therapeutic strategies.