A Twist in the Progression of Atherosclerosis
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Atherosclerosis is a dangerous condition caused by molecular damage to certain proteins circulating in the blood and then spurred on by growing chronic inflammation in aging. Where it takes root, the walls of your arteries corrode, malform, and expand inward into soft plaques of degenerative material. This is largely formed of macrophage cells attracted to the area by dysfunctional signaling and then choked by the debris. Ultimately this leads to serious vascular dysfunction, but more importantly if a large enough chunk of plaque material breaks away it will cause a heart attack or stroke.

Here researchers suggest that the immune system is not the dominant origin for the macrophages that make up plaque debris, and a more important and unusual source is actually closer at hand:

Scientists [have identified] a long-overlooked function of vascular smooth muscle cells in atherosclerosis. Atherosclerosis [is] a chronic inflammatory disease of the arteries arising from interactions of modified lipoproteins and various cell types including monocyte-derived macrophages from the blood and smooth muscle cells (SMCs) in the vessel wall. "It is unclear, however, how each particular cell type contributes to the development of an atherosclerotic lesion. One highly controversial issue is the contribution of vascular SMCs to plaque growth."

[The] researchers performed lineage tracing experiments in mice, in which they have genetically labeled mature SMCs in the vessel wall of young mice before the onset of the disease and then monitored their fate in older atherosclerotic animals. "Surprisingly, we found that SMCs in the arterial wall can undergo clonal expansion during disease progression and convert into macrophage-like cells that have lost the classical SMC marker, α-smooth muscle actin. It seems that certain atherosclerotic lesions contain even more SMC-derived macrophages than traditional monocyte-derived macrophages."

These findings indicate that previous studies based on immunostaining of plaque cells for smooth muscle and macrophage markers have vastly underestimated the role of SMCs and overestimated the role of monocyte-derived macrophages in atherosclerosis. "Targeting SMC-to-macrophage transdifferentiation could be a novel therapeutic strategy to treat atherosclerotic heart disease and perhaps many other diseases with a smooth muscle component."

Link: http://www.uni-tuebingen.de/en/landingpage/newsfullview-landingpage/article/was-die-arterien-verstopfen-kann.html

Comments

"Atherosclerosis is a dangerous condition caused by molecular damage to certain proteins circulating in the blood [...]" Proteins? Aren't oxidated cholesterol derivatives the primary culrpits? They're not proteins.

Anyway, this finding is important to SENS because it bears on which cells need to be targetted with the transgenic lysosomal enzymes. Last I heard they were trying to transfer the therapy from fibroblasts into macrophages, but with this result it seems that targetting just those cells may not be sufficient. On the other hand, there's now a new opportunity to try a different cell type if the macrophages weren't co-operating.

A reaction to this finding from someone close to the project would be warranted I think.

Posted by: José at August 13, 2014 1:19 PM

@José: Lipoproteins would have been a better choice of word there, yes.

Posted by: Reason at August 13, 2014 4:17 PM
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