In atherosclerosis, monocytes enter the intima of the vessel and differentiate into macrophages and dendritic cells. Usually in reviews and lectures, foam cells are shown to stay there and finally undergo apoptosis, leading to growth of the atherosclerotic lesion. But is it also possible for macrophages and even foam cells to leave the intima before apopotosis occurs by crossing the endothelium?
This paper is a good starting point to answer your question
J Clin Invest. 2011 May;121(5):2025-36. doi: 10.1172/JCI43802. Epub 2011 Apr 18.
Suppressed monocyte recruitment drives macrophage removal from atherosclerotic plaques of Apoe-/- mice during disease regression.
This paper is a good starting point to answer your question
J Clin Invest. 2011 May;121(5):2025-36. doi: 10.1172/JCI43802. Epub 2011 Apr 18.
Suppressed monocyte recruitment drives macrophage removal from atherosclerotic plaques of Apoe-/- mice during disease regression.
Foamy cell can still migrate out. The ratio of immigrating/recruited new monocytes to emigrated foam cells makes the important difference. Check this as a starting point
Am J Pathol. 1981 May;103(2):191-200.
The role of the monocyte in atherogenesis: II. Migration of foam cells from atherosclerotic lesions.
Gerrity RG.
Abstract
A defined role in the atherogenic sequence is proposed for the circulating monocyte. The author has been able to demonstrate a "monocyte clearance system" in which large numbers of circulating monocytes invade the intima of lesion-prone areas in arteries, become phagocytic, and accumulate lipid. A fatty cell lesion results. Once lipid-laden, foam cells migrate back into the bloodstream by crossing the arterial endothelium. The ratio of penetrating monocytes to emerging foam cells decreases as fatty cell lesions develop until a one-to-one ratio is achieved in late fatty cell lesions, which do not progress further. Advanced fibroatherosclerotic plaques in the same animals do not show the same characteristics and have smooth muscle cell involvement. It would appear that advancement of the lesion is at least partially a result of failure of the monocyte clearance system to remove sufficient lipid. The invasion of monocytes and endothelial damage caused by foam cell clearance may, in late fatty lesions, contribute to plaque evolution by introducing growth factors from macrophages and platelets and allowing greater lipid influx. Elucidation of this system was facilitated by the examination of vessels from diet initiation onwards and by the observation of late nonprogressing fatty cell lesions. It is possible that this system exists in other models but has been overlooked by a predilection for the study of advanced lesions that prevails in the literature.
According to Ross Gerrity and Chris Haslett - two of the great macrophage biologists (Gerrity Am J Path 1981 ; Bellingan et al J Immunol 1996) - they CAN leave the intima.
Certainly. Another interesting report: J Clin Invest. 2010 Dec;120(12):4415-24. doi: 10.1172/JCI38911. LXR promotes the maximal egress of monocyte-derived cells from mouse aortic plaques during atherosclerosis regression.
Dr Nass you have good answers to your question. I believe; however, as pointed out by Arciniegas et al Am J Physiol Lung Cell Mol Physiol. 2007 Jul;293(1):L1-8.that in the intima transdiferentiation often occurs. The complexity of the aterosclrotic plaque seem to suggest several mechanisms for cell trafic and death. Foam cells and macrophages in the intima could be the product of transdiferentiation. These trandiferentiated cells undergo efferocytosis or paroptosis rather tan apoptosis and therefore could exit the intima as shown by the reports presented in the previous answers.
Recommend to search for the article from A. A. Francis and G. N. Pierce
"An integrated approach for the mechanisms responsible for atherosclerotic plaque regression" to learn about the migration process of macrophages during ATS regression.
Highly descriptive recent article + fairly illustrative picture included! :)
Yes, Foam cells can leave the subemdothelium space if it is injured. by inflammatory factors, oxidative stress. thrombotic conditions.
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