Limits to Growth of Native Collateral Vessels

Abstract

See related article, pages 89–98 The presence of a functional collateral circulation can have great importance for clinical symptoms as well as for clinical decision making. When experiencing an acute myocardial infarction, most patients have severe symptoms, call for emergency, and are treated rapidly and effectively given a functioning infrastructure for primary percutaneous coronary interventions. In contrast, other individuals experience few symptoms, and some may not even notice their infarction. One possible explanation for the attenuated symptoms in the second group of patients is the presence of functional coronary collateral vessels, which are capable of supplying significant amounts of blood into an otherwise completely ischemic myocardium. In fact, the significant variability of native collateral conductance in humans is well established.1 Moreover, the genetic background had been identified as a denominator of the presence of collateral vessels in mice as different mouse strains show major differences with regard to the presence of collaterals.2,3 The study by Chalothorn et al, published in this issue of Circulation Research ,4 provides a potential explanation for the interindividual variability of the presence of functional collateral vessels. In fact, data from both the peripheral circulation (hindlimb model), as well as from the cerebral circulation of a mouse model support the idea that the absence of the CLIC4 gene, ie, the gene encoding chloride intracellular channel-4, is related to the presence of fewer (approximately one-third) collateral vessels in adult mice. Likewise, the diameter of the collaterals was slightly (roughly 30%) reduced. Of interest, hemizygous CLIC+/− mice showed an intermediate phenotype with regard to collateral number and size. The novel data from Chalothorn et al focus on differences in native collateral vessels. This refers to the process of creating arterio-arterial anastomoses during embryonic and early postnatal life in the absence of any existing …