Therapeutic Angiogenesis of Chinese Herbal Medicines in Ischemic Heart Disease: A Review

Recent discoveries of endogenous negative regulators of angiogenesis, thrombospondin, angiostatin and glioma-derived angiogenesis inhibitory factor, all associated with neovascularized tumours, suggest a new paradigm of tumorigenesis. It is now helpful to think of the switch to the angiogenic phenotype as a net balance of positive and negative regulators of blood vessel growth. The extent to which the negative regulators are decreased during this switch may dictate whether a primary tumour grows rapidly or slowly and whether metastases grow at all.

Higher organisms rely on a closed cardiovascular circulatory system with blood vessels supplying vital nutrients and oxygen to distant tissues. Not surprisingly, vascular pathologies rank among the most life-threatening diseases. At the crux of most of these vascular pathologies are (dysfunctional) endothelial cells (ECs), the cells lining the blood vessel lumen. ECs display the remarkable capability to switch rapidly from a quiescent state to a highly migratory and proliferative state during vessel sprouting. This angiogenic switch has long been considered to be dictated by angiogenic growth factors (eg, vascular endothelial growth factor) and other signals (eg, Notch) alone, but recent findings show that it is also driven by a metabolic switch in ECs. Furthermore, these changes in metabolism may even override signals inducing vessel sprouting. Here, we review how EC metabolism differs between the normal and dysfunctional/diseased vasculature and how it relates to or affects the metabolism of other cell types contributing to the pathology. We focus on the biology of ECs in tumor blood vessel and diabetic ECs in atherosclerosis as examples of the role of endothelial metabolism in key pathological processes. Finally, current as well as unexplored EC metabolism-centric therapeutic avenues are discussed. © 2015 American Heart Association, Inc.

Vascular endothelial growth factor (VEGF) can promote angiogenesis but may also exert certain effects to alter the rate of atherosclerotic plaque development. To evaluate this potential impact on plaque progression, we treated cholesterol-fed mice doubly deficient in apolipoprotein E/apolipoprotein B100 with low doses of VEGF (2 microg/kg) or albumin. VEGF significantly increased macrophage levels in bone marrow and peripheral blood and increased plaque area 5-, 14- and 4-fold compared with controls at weeks 1, 2 and 3, respectively. Plaque macrophage and endothelial cell content also increased disproportionately over controls. In order to confirm that the VEGF-mediated plaque progression was not species-specific, the experiment was repeated in cholesterol-fed rabbits at the three-week timepoint, which showed comparable increases in plaque progression.