Progression of Arterial Vasa Vasorum from Regulator of Arterial Homeostasis to Promoter of Atherogenesis

The vasa vasorum (vessels of vessels) are a dynamic microvascular system uniquely distributed to maintain physiological homeostasis of the artery wall by supplying nutrients and oxygen to the outer layers of the artery wall, adventitia, and perivascular adipose tissue (PVAT), and in large arteries, to the outer portion of the medial layer. Vasa vasorum endothelium and contractile mural cells regulate direct access of bioactive cells and factors present both in the systemic circulation and in the arterial PVAT and adventitia to the artery wall. Experimental and human data show that proatherogenic factors and cells gain direct access to the artery wall via the vasa vasorum and may initiate, promote, and destabilize the plaque. Activation and growth of vasa vasorum occurs in all blood vessel layers primarily by angiogenesis, producing fragile and permeable new microvessels that may cause plaque hemorrhage and fibrous cap rupture. Ironically, invasive therapies such as angioplasty and coronary artery bypass grafting injure the vasa vasorum leading to treatment failures. The vasa vasorum function as a master integrator of both arterial homeostasis and once perturbed or injured, as a promotor of atherogenesis. Future studies need to be directed at establishing reliable in vivo and in vitro models to investigate the cellular and molecular regulation of the function and dysfunction of the arterial vasa vasorum.