Ying Wang, Vivek Nanda, Daniel Direnzo, Jianqin Ye, Sophia Xiao, Yoko Kojima, Kathryn L Howe, Kai-Uwe Jarr, Alyssa M Flores, Pavlos Tsantilas, Noah Tsao, Abhiram Rao, Alexandra A C Newman, Anne V Eberhard, James R Priest, Arno Ruusalepp, Gerard Pasterkamp, Lars Maegdefessel, Clint L Miller, Lars Lind, Simon Koplev, Johan L M Björkegren, Gary K Owens, Erik Ingelsson, Irving L Weissman, Nicholas J Leeper
Atherosclerosis is the process underlying heart attack and stroke. Despite decades of research, its pathogenesis remains unclear. Dogma suggests that atherosclerotic plaques expand primarily via the accumulation of cholesterol and inflammatory cells. However, recent evidence suggests that a substantial portion of the plaque may arise from a subset of "dedifferentiated" vascular smooth muscle cells (SMCs) which proliferate in a clonal fashion. Herein we use multicolor lineage-tracing models to confirm that the mature SMC can give rise to a hyperproliferative cell which appears to promote inflammation via elaboration of complement-dependent anaphylatoxins...
June 15, 2020: Proceedings of the National Academy of Sciences of the United States of America