Coronary collateral growth—Back to the future

Abstract

The coronary collateral circulation is critically important as an adaptation of the heart to prevent the damage from ischemic insults. In their native state, collaterals in the heart would be classified as part of the microcirculation, existing as arterial-arterial anastomotic connections in the range of 30 to 100 μM in diameter. However, these vessels also show a propensity to remodel into components of the macrocirculation and can become arteries larger than a 1000 μM in diameter. This process of outward remodelling is critically important in the adaptation of the heart to ischemia because the resistance to blood flow is inversely related to the fourth power of the diameter of the vessel. Thus, an expansion of a vessel from 100 to 1000 μM would reduce resistance (in this part of the circuit) to a negligible amount and enable delivery of flow to the region at risk. Our goal in this review is to highlight the voids in understanding this adaptation to ischemia—the growth of the coronary collateral circulation. In doing so we discuss the controversies and unknown aspects of the causal factors that stimulate growth of the collateral circulation, the role of genetics, and the role of endogenous stem and progenitor cells in the context of the normal, physiological situation and under more pathological conditions of ischemic heart disease or with some of the underlying risk factors, e.g., diabetes. The major conclusion of this review is that there are many gaps in our knowledge of coronary collateral growth and this knowledge is critical before the potential of stimulating collateralization in the hearts of patients can be realized.

miR-21-mediated decreased neutrophil apoptosis is a determinant of impaired coronary collateral growth in metabolic syndrome

“…Taken together, these findings suggest a scenario in which aberrant prolonged survival of neutrophils in combination with excessive VSMC proliferation (13) create an environment that is not conducive to collateral expansion. It is currently thought that as collateral remodeling progresses and HIF-1␣ levels decline as ischemia diminishes, increasing NO induced by increasing shear stress carries on continuing remodeling (4). Under certain conditions, NO has been shown to stimulate the mitochondrial apoptotic pathway by directly disrupting the mitochondrial membrane potential, leading to cytochrome-c release and subsequent caspase-9 activation (2) through unknown mechanisms.…”

State-of-the-Art Methods for Evaluation of Angiogenesis and Tissue Vascularization

“…By definition, collateral vessels provide artery-to-artery connections and are thought to play a protective role by providing alternative routes to blood flow. 102 …”

Collateral Development

“…In the heart, arterialarterial anastomoses (20-200-μm diameter) are incapable of conducting sufficient blood flow to support cellular metabolism because of their small caliber and lack of muscularity. 5,7,12 Environmental stimuli, such as changes in physical forces (eg, shear stress) or ischemia because of vascular occlusion from atherosclerotic disease, lead to increased growth factor expression. 13,14 The endothelium, in response to these stimuli, recruits immune cells and endothelial progenitor cells, which secrete more growth factors to stimulate smooth muscle cell recruitment.…”