Inflammatory angiogenesis in atherogenesis - A double-edged sword

Domenico Ribatti, Francesca Levi-Schaffer, Petri T. Kovanen

Research output: Contribution to journalArticlepeer-review


The adventitia and the outer layers of media of an atherosclerosis-prone arterial wall are vascularized by vasa vasorum. Upon growth of an atherosclerotic lesion in the intima, neovascular sprouts originating from the adventitial vasa vasorum enter the lesion, the local proangiogenic micromilieu in the lesion being created by intramural hypoxia, by increased intramural oxidant stress, and by inflammatory cell infiltration (macrophages, T cells and mast cells). The angiogenic factors present in the lesions include various growth factors, chemokines, cytokines, proteinases, and several other factors possessing direct or indirect angiogenic activities, while the current list of antiangiogenic factors is smaller. An imbalance between endogenous inducers and inhibitors of angiogenesis, with a predominance of the former ones, is essential for the development of neovessels during the progression of the lesion. By providing oxygen and nutrients to the cells of atherosclerotic lesions, neovascularization initially tends to prevent cellular death and so contributes to plaque growth and stabilization. However, the inflammatory cells may induce rupture of the fragile neovessels, and so cause intraplaque hemorrhage and ensuing plaque destabilization. Pharmacological inhibition of angiogenesis in atherosclerotic plaques with ensuing inhibition of lesion progression has been achieved in animal models, but clinical studies aiming at regulation of angiogenesis in the atherosclerotic arterial wall can be designed only after we have reached a firm conclusion about the role of angiogenesis at various stages of lesion development - good or bad.

Original languageEnglish
Pages (from-to)606-621
Number of pages16
JournalAnnals of Medicine
Issue number8
Publication statusPublished - 2008


  • Angiogenesis
  • Atherosclerosis
  • Carotid disease
  • Coronary disease
  • Hypercholesterolemia
  • Inflammation
  • Mast cells
  • Thrombosis

ASJC Scopus subject areas

  • Medicine(all)


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