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New vessel growth in chronic ischemic syndromes is an attractive idea. Fortunately, more than one mechanism exists to create new blood vessels. Angiogenesis is the creation of blood vessels from sprouts off the existing vessels. In contrast, vasculogenesis is the creation of de novo blood vessels by differentiation of new blood cells. Endothelial cell precursors in the bone marrow and circulating in the bloodstream can integrate into developing vessels and contribute to vessel growth in a manner similar to the vasculogenesis of embryonic development. The therapeutic potential of these cells has not been tested, but they can be recruited from bone marrow and may be a means to accelerate endogenous revascularization in patients with ischemia.

Mechanisms of Arteriogenesis and Development of Collateral Vessels

FIG 14.2 Mechanisms of Arteriogenesis and Development of Collateral Vessels. ECs, Endothelial cells; GM-CSF, granulocyte macrophage colony-stimulating factor; ICAM-1, intercellular adhesion molecule 1; IL-4, interleukin-4; LAD, left anterior descending artery; MCP-1, monocyte chemotactic protein 1; RCA, right coronary artery; SMCs, smooth muscle cells.

In contrast to angiogenesis, arteriogenesis or collaterogenesis is the recruitment of existing vessels to increase their capacity and consequent blood flow to ischemic tissue (Fig.14.2). Arteriogenesis represents the maturation of vessels that exist but that may not contribute significantly to regional blood flow until properly stimulated. Most collateral vessels visualized by arteriography are probably vessels that have undergone arteriogenesis instead of angiogenesis. Because arteriogenesis creates capacitance vessels, this process is more likely to increase blood supply in a way that substantially affects tissue perfusion. The proteins that affect arteriogenesis are distinct from those that regulate angiogenesis. VEGF does not seem to be important for arteriogenesis, whereas macrophage-derived factors are necessary. The therapeutic potential of arteriogenesis has not been tested, but because of the role of arteriogenesis in collateral formation in patients with chronic myocardial ischemia, arteriogenesis represents another potential therapeutic tool for the creation of new blood vessels in patients with refractory angina.