In the absence of disease, microvessels provide vessel wall nutrients to the tunica media, while the intima is fed by
oxygen diffusion from the lumen. As disease evolves and the tunica intima thickens,
oxygen diffusion is impaired, and microvessels become the major source for nutrients to the vessel wall. Microvessels serve as a port of entry for inflammatory cells, from the systemic circulation to the nascent atherosclerotic lesion. As disease progress, microvessels also play a role in intraplaque
hemorrhage,
lipid core expansion, and plaque
rupture. In addition, microvessels are also involved in
stent restenosis, and plaque regression. Therefore, microvessels are a pivotal component of
atherosclerosis, and proper patient risk-stratification in the near future may include the detection of increased neovascularization in atherosclerotic lesions. This review divided in two parts summarizes the current understanding of
atherosclerosis neovascularization, starting with the normal anatomy and physiology and progressing to more advanced stages of the disease. We will review the structure and function of vasa vasorum in health and disease, the mechanisms responsible for the angiogenic process, the role of the immune system, including
inflammation and
Toll-like receptors, and the pathology of microvessels in early
atherosclerotic plaques. Furthermore, the review addresses the advanced stages of
atherosclerosis, summarizing the progressive role for microvessels during
disease progression, red blood cell extravasation,
lipid core expansion, plaque
rupture, healing, repair, restenosis, and disease regression, offering the clinician a state-of-the-art, "bench to bedside" approach to neovascularization in human
atherosclerosis.