**Coronary Collateral Growth: Clinical Perspectives and Recent Insights Recent Insights**

**Coronary Collateral Growth: Clinical Perspectives and** 

Bhamini Patel, Peter Hopmann, Mansee Desai, Kanithra Sekaran, Kathleen Graham, Liya Yin and William Chilian Mansee Desai, Kanithra Sekaran, Kathleen Graham, Liya Yin and William Chilian

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/67164

Bhamini Patel, Peter Hopmann,

#### **Abstract**

This chapter summarizes recent research on the coronary collateral circulation. The chapter is focused on clinical perspectives and importance of a well-developed coronary collateral circulation, the mechanisms of growth induced by chemical factors and a role for stem cells in the process. Some discussion is devoted to the role of shear stress and mechanical signaling, but because this topic has been reviewed so extensively in the recent past, there is only small mention of its role in the growth of the coronary collateral circulation.

**Keywords:** arteriogenesis, coronary collateral, ischemic heart disease

## **1. Introduction**

Although arteriogenesis has been studied for approximately a hundred years, there are still fundamental unanswered questions about the causes of collateral vessel growth, and whether different factors control growth at varying points in the maturation process. One line of investigation, spurred by the myriad contributions of Schaper and his colleagues have focused on mechanical shear stress being the main factor that stimulates collateral growth [1–4]. Although this hypothesis is well-founded on a large body of experimental data, it does not explain other observations that show collateral growth in the absence of altered shear stress [5, 6]. Accordingly investigators have proposed that ischemia (via cytokine, chemokine, and growth factor expression), and the consequential inflammation, is the cause of collateral growth, but

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

assessing it has proven to be difficult due to the unclear lines between ischemic regions, normal circulation, and collateral growth. The hypotheses regarding the causative factor(s) for collateral growth are not mutually exclusive as there are likely many mechanisms that are the principal driver, which vary at various points of the process. For example, even if one maintains that ischemia is the initiating mechanism for collateral growth, it is likely that other stimuli continue the growth of the vessel after the ischemic stimulus has waned. To provide perspective for this chapter, we refer to **Figure 1**, which summarizes four factors that exert important effects in this adaptive process. The bulk of this chapter will focus on the collateral growth from a clinical perspective, the role of stem cells, and chemical factors involved in this process. We will not extensively review the role that shear stress in coronary collateral growth as this has been reviewed ample times in the past. We also will not review the genetic aspects because the bulk of this information has been derived from studies of collateral growth in vascular beds other than the heart, e.g., skeletal muscle and brain [7, 8], although there is some preliminary information about genetic links to collateral growth in patients [9]. **Figure 1** also shows the anatomical structure of a collateral; namely, an arterial-arterial anastomosis that connect large coronary perfusion territories. Collateral growth, also known as arteriogenesis, in the heart involves the abluminal expansion of a preexisting arterial-arterial anastomosis [10]. The degree of expansion is profound—the caliber of collateral vessels can increase over an order of magnitude [10]. This degree of expansion would greatly reduce vascular resistance of these vessels, thereby increasing flow in the area of risk. This increase in flow is the reason why the collateral circulation exerts beneficial effects through the reduction in infarct size (following a coronary occlusive event) and reduction in the incidence of sudden cardiac death.

We also would like to point out an obvious distinction between the growth of collateral vessels (arteriogenesis) and angiogenesis. These processes are often confused as the same, but

 **Figure 1.** An image of the human coronary circulation depicting large collateral vessels that connect perfusion territories of major arteries and some factors that regulate their development.

they are distinct and have distinguishing characteristics. In *A Brief Etymology of the Collateral Circulation*, Faber et al. describe angiogenesis as the formation of capillaries from preexisting capillaries [11]. In contrast to angiogenesis, arteriogenesis is more the remodeling of preexisting vessels through the "anatomic increase in lumen area and wall thickness." The causes of arteriogenesis are more physical, specially, mechanical shear stress and ischemic conditions, while angiogenesis is caused by chemical conditions such as hypoxia [11].
