Coronary Collateral Growth and Its Therapeutic Application to Coronary Artery Disease

Abstract

Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp or a long time, the functional role of the coronary collateral circulation as a blood-conveying channel has been disputed. 1-4 Because a well-developed coronary collateral circulation is usually associated with severe coronary stenosis, some investigators assumed that the existence of collateral circulation is a marker of coronary artery disease (CAD). 1 Over the past 3 decades, accumulating evidence has documented that pre-existing well-developed coronary collateral circulation at the onset of acute myocardial infarction plays an important functional role in preserving left ventricular function, 2,5 reducing infarct size, 6 preventing left ventricular aneurysm formation 7 and survival. 2 Thus, a significant functional role of coronary collateral circulation is now well appreciated. 8 In the past decades, 9-11 we and others have emphasized the importance of arteriogenesis of the collateral vessels for enhanced coronary collateral circulation, compared with angiogenesis of the capillaries in areas perfused by occluded or critically stenosed coronary arteries. On the other hand, there has been considerable controversy concerning the stimulus for coronary collateral growth. It is now clear that long-standing high-grade coronary stenosis is mainly responsible for collateral vessel growth. 12 Severe coronary narrowing results in myocardial ischemia and a pressure gradient between the providing and receiving coronary arteries across the collateral network. New establishment of a pressure gradient leads to recruitment of collateral blood flow and increased shear stress at the site of pre-existing collateral vessels. Thus, severe coronary narrowing is inevitably accompanied by 2 potential stimuli for the development of collateral circulation, namely, myocardial ischemia and shear stress.One of the hot topics of coronary collateral growth is the role of bone-marrow-derived stem or endothelial progenitor cells in arteriogenesis. 13-16 It is still controversial whether these cells contribute to collateral growth by supplying cytokines and proteases related to arteriogenesis or by building up the collateral vessel as a result of the incorporation of these cells into vessel walls. 17 Thus, this review constitutes a summary of the historical background and current knowledge of coronary collateral growth in reference to the therapeutic potential for treating CAD. Stimulus of Coronary Collateral Growth Animal ModelsFor a long time, there was no general idea concerning the principal stimulus for coronary collateral growth. In 1967, Schaper proposed a new concept concerning the importance of mechanical factors on collateral growth. 18 He emphasized the crucial role of increased tangential (radial) shear stress at small pre-existing collateral arterioles, which results from increased intravascular pressure and arteriolar dilatation.In contrast, Scheel et al considered that myocardial ischemia is important for coronary collateral growt...

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