Bone-marrow-derived smooth muscle cells may play role in the development of atherosclerotic plaque

Atherosclerosis is the major cause of adult mortality in the developed world, and a significant contributor to atherosclerotic plaque progression involves smooth muscle cell recruitment to the intima of the vessel wall. Controversy currently exists on the exact origin of these recruited cells. The authors studied sex-mismatched bone marrow transplant subjects in order to determine whether smooth muscle cells throughout the atherosclerotic vessel wall can derive from donor bone marrow. The researchers looked at coronary artery autopsy specimens from 13 patients who had undergone a bone marrow transplant. Eight had received marrow from donors of the opposite sex, and all patients had survived for a month or more after transplant with clinical report of engraftment. By combining immunostaining for smooth muscle cell markers with fluorescence in situ hybridization for X and Y chromosomes, they found that smooth muscle cells throughout the atherosclerotic wall could derive from the bone marrow of the sex-mismatched donors - with the contribution more than 10% of total cells in many cases. The authors found that in the sex-mismatched transplant recipients, the percentage of opposite-sex smooth muscle cells in the intima, media, and adventitial microvessels of diseased coronary artery segments was "100-fold" than that seen in the same layers of non-diseased segments in the same subjects.Furthermore, the authors noted an extensive recruitment of these cells in diseased compared with non-diseased segments - enrichment which was not caused by recipient smooth muscle cells fusing with bone marrow. The researchers state that the exact role of the bone-marrow-derived smooth muscle cells remained unknown."This is can be argued in one of two ways," said lead researcher Caplice. "One is that the smooth muscle cells contribute to plaque development and plaque volume. The other possibility, one that is attractive to us and more likely, is that the cells are recruited in response to injury. They could be there in a way to try and heal the plaque by forming a fibrous scar over the areas of inflammation."Caplice went on to explain that the progenitor cells produced by the marrow tend to stick to existing plaques, and if they can be kept from progressing to become smooth-muscle cells, or if their 'stickiness' is affected so they do not congregate at the plaque site, the worsening of atherosclerosis may be prevented. The authors conclude that their data has broad implications for the understanding of the cellular components of human atherosclerotic plaque and provide a potentially novel target for future diagnostic and therapeutic strategies. They call for further research to fully identify whether the smooth muscle precursors potentiate the expansion of plaque volume or serve a protective function in human plaque by augmenting fibrous cap strength and cap stability.Reference...