Angiogenesis in atherosclerosis: gathering evidence beyond speculation

Abstract

Greater knowledge of plaque angiogenesis regulation is needed to design treatments that target the most critical regulatory pathways. Evolutions in angiogenesis inhibitor treatments for cancer and other diseases call for a need to understand the distinct cardiovascular profiles of different agents to rationally combine agents for optimal selectivity and efficacy in the intended vascular bed.

Letter by Reynolds et al Regarding Article, “Risk of Bleeding With 2 Doses of Dabigatran Compared With Warfarin in Older and Younger Patients With Atrial Fibrillation: An Analysis of the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) Trial”

“…Atherosclerotic lesions are known to have neovascularization with friable vessels and may be prone to leaking, and we suggest that the bleeding in these tissues may be more related to a metabolically active tissue associated with immature blood vessels and a higher cellular turnover. 4 We agree with the authors that a greater risk of gastrointestinal bleeding with dabigatran may be the result of local effects, particularly given that despite the very low bioavailability of dabigatran etexilate, none is detectable in feces. 5 This suggests that unabsorbed dabigatran etexilate is locally hydrolyzed to active drug, which, although not absorbable, is presentable to gastrointestinal microvasculature that may be compromised (ie, diverticulosis).…”

Intravital Microscopy on Atherosclerosis in Apolipoprotein E–Deficient Mice Establishes Microvessels as Major Entry Pathways for Leukocytes to Advanced Lesions

“…An association between microvascular density and leukocyte content has also been suggested by data from de Boer et al 33 and Ionita et al 34 However, the spatial association between microvessels and leukocytes in lesions may not be an effect of recruitment of leukocytes from these vessels but may reflect secretion of angiogenic factors from immune cells and subsequent growth of vessels into inflamed areas. 35 Apparently, the present study fills an important gap in our understanding of the role of microvessels in atherosclerotic lesions by demonstrating that endothelium in lesional venules, but not arterioles or capillaries, is highly capable of recruiting leukocytes to lesions. Although we demonstrate the importance of lesion venules in the accumulation of leukocytes in mice, the microvascular recruitment pathway could be even more significant in human lesions, which carry more extensive microvascular networks because of their size and nutritional requirements.…”

VEGF Receptor-2 Variants Are Associated With Susceptibility to Stroke and Recurrence

“…Recent studies show that increased density of microvessels within the plaque area contributes to the growth and destabilization of the plaque, whereas in stable plaques, there is a marked decrease in the density of immature "leaky" microvessels. 6,7 Upregulation of VEGF signaling has been linked to neovascularization within the plaque. 8,9 Therefore, quenching VEGF signaling such as downregulated expression of VEGF receptor-2 would retard the plaque growth and reduce the risk of atherothrombotic stroke in persons with plaque lesions.…”