With the in-depth study of atherosclerosis (As), promoting the stability of vulnerable plaque has become a new therapeutic concept for As. In the “inside-out” theory of As, the pathological changes of the intima are the initiating factors. However, recent studies have shown that the vasa vasorum (VV) plays a key role in the pathogenesis of As from the outside to the inside. In summary, treatment of As has changed from protecting the intima to regulating the outer membrane VV.