Following arterial injury from balloon angioplasty, smooth muscle cells (SMCs) proliferate within the vessel wall, narrowing the vessel and often restricting blood flow to a dangerous degree.
Within the neointima, these vascular SMCs deposit collagens and other ECM components, which they bind and interact with in various ways. Considerable effort has centered on the adhesive receptors expressed during neointima formation, and Hou et al. show here that a novel collagen receptor, unrelated structurally or functionally to the better-studied integrin family of ECM receptors, plays a key role in this pathological response.
The discoidin domain protein DDR1 is a member of a small family of receptor tyrosine kinases that bind collagens in soluble or insoluble form and directly transduce signals across the plasma membrane. Knockout mice lacking this protein are viable and normal in many respects, including the structure of their arteries.
However, SMCs from these animals are specifically deficient in their ability to adhere to or migrate on collagen, prompting Hou and colleagues to examine the responses of DDR1/ mice to arterial injury. The authors find that, following angioplasty in the carotid artery, the mutant animals form a dramatically smaller neointima than do wild-type controls, raising the hope that inhibition of DDR1 at the time of treatment could repress this response in humans as well.
Hou et al. also speculate that the contribution of SMCs to atherosclerotic lesions could be affected by the loss of DDR1 function, an idea they propose to test by crossing the DDR1 mutation into an atherosclerosis-prone genetic background.