Immune mechanisms in atherosclerosis.
To summarize, it is possible that T cell activation in the plaque has four different effects: a direct inhibition of smooth muscle proliferation mediated by IFN-gamma, an indirect stimulation of smooth muscle proliferation via IFN-induced macrophage activation, an induction of responsiveness to PDGF by induction of PDGF receptor expression, and finally, an up-regulation of HDL receptors. The net effect of T cell activation during the vascular response to injury may, therefore, depend on the balance between these mechanisms in any given situation during lesion development. T cell activation may itself be regulated by apolipoprotein E-containing LDL, which thus could form a direct link between lipoprotein accumulation and immune activation. We have recently tried to assess the effect of T cell activation during the response to experimental arterial injury with the use of a drug model. Cyclosporin A is a drug that specifically inhibits T cell activation. Rats treated with cyclosporin A for a short period had significantly smaller intimal lesions than did controls after balloon injury. This could be due to an inhibition of T cell activation, resulting in an inhibition of monocyte-macrophage activation and thereby loss of an important stimulus for intimal cell proliferation. When interpreting these results, one must, however, bear in mind that cyclosporin A could exert as yet unknown nonimmune vascular effects. It is also worth stressing that cell proliferation in the human atherosclerotic plaque may not be as high as in experimental animal lesions. In fact, cell replication may be a very rare event in the average advanced atherosclerotic plaque. Cell proliferation may, however, be associated with an episodic growth of lesions, and growth factor-mediated responses could, therefore, be important for the eventual clinical outcome in the individual patient. In conclusion, cytokines produced during the immune response affect growth and differentiation of vascular cells and could modulate both the response to injury and the local lipid metabolism in an atherosclerotic plaque There is indirect support for paracrine secretion of several of these factors in the atherosclerotic plaque, and activated T lymphocytes and macrophages are abundant in the plaque. This points to the possibility that specific immune responses are associated with the development of atherosclerosis. It is unknown, however, to what extent such immune responses occur or which antigens may elicit these responses.
- Copyright © 1989 by American Heart Association