The development of atherosclerotic diseases involves the proliferation and migration of a variety of cell types. It has been generally accepted that vascular smooth muscle cells in the arterial wall play a crucial role in this process through a process of ‘de-differentiation’ from a normal contractile phenotype to a proliferative and synthetic state that drives remodelling and disease development. In this study, Tang et al re-examine this paradigm and provide compelling evidence to challenge the status quo. Using sophisticated in-vitro lineage tracing techniques, they initially identified a novel type of stem cell which they dub a multipotent vascular stem cell (MVSC). Under normal physiological conditions these MVSCs replenish normal smooth muscle cells to maintain vascular integrity and function, but in response to vascular injury, the MVSCs undergo proliferative change and produce phenotypically abnormal smooth muscle cells. Therefore, rather than a process of ‘de-differentiation’ of mature cells, atherosclerosis is elegantly demonstrated to be a disease of stem cells, switching attention to a new target in understanding the basic pathophysiology behind myocardial infarction and stroke.
Multipotent vascular stem cells affected by vascular injury undergo differentiation into abnormal proliferative smooth muscle cells characteristic of atherosclerosis. This new evidence re-targets atherosclerosis as a stem-cell disease, not only providing fundamental new insights into vascular biology but potentially providing new therapeutic targets in cardiovascular disease
- Tang Z, Wang A, Yuan F, Yan Z, Liu B, Chu JS, Helms JA, Li S. Differentiation of multipotent vascular stem cells contributes to vascular diseases. Nat Commun. 2012 Jun 6;3:875.