Abstract 392: High-Density Lipoproteins Beneficially Regulate Angiogenesis
Introduction: Angiogenesis can be both favourable and unfavourable. It is critical for collateral vessel formation in response to ischaemia following myocardial infarction (MI), however excessive inflammatory-driven neovascularisation accelerates atherosclerotic plaque growth. High-density lipoproteins (HDL) are associated with improved survival and prognosis following MI as well as reduced plaque development.
Hypothesis: We hypothesized that HDL may beneficially regulate angiogenesis under both hypoxic or inflammatory settings, in vitro.
Methods and results: Human coronary artery endothelial cells (HCAECs) subjected to hypoxia (1.2% O2, 6h) displayed increased tubulogenesis (19%) and proliferation (31%), p<0.05. Interestingly, pretreatment with reconstituted HDL (rHDL), containing apolipoprotein (apo)A-I and phosphatidylcholine, augmented hypoxia-driven elevations in tubulogenesis (14%) and proliferation (53%), p<0.05. Consistent with this, rHDL also augmented hypoxia-driven elevations in the proangiogenic mediators HIF1α (39%), VEGF (1.5 fold) and SDFα (3.4 fold), p<0.05. In contrast to the findings in hypoxia, pre-treatment with rHDL followed by exposure to two inflammatory conditions: TNFα (0.7 ng/ml) and stimulated macrophage-conditioned media (CM), significantly inhibited HCAEC tubulogenesis (75% & 70%), proliferation (47% & 39%) and migration (37% & 55%), p<0.05. The anti-angiogenic effects of rHDL in both inflammatory settings were associated with reductions in the pro-angiogenic inflammatory mediators p65 (43% & 52%) and MCP-1 (33% & 30%), p<0.05. Moreover, in contrast to the setting of hypoxia, rHDL reduced HIF1α and VEGF protein in response to inflammation (TNFα (36% & 34%) and CM (37% & 19%), p<0.05). rHDL pretreatment strikingly increased hemeoxygenase-1 (HO-1) protein expression, a known regulator of angiogenesis, under both hypoxic and inflammatory conditions (∼2-4 fold for all), p<0.05.
Conclusions: In summary, we have identified HDL to uniquely regulate angiogenesis, characterized by enhancement of hypoxia-mediated angiogenesis and, conversely, marked suppression of inflammation-associated angiogenesis.
- © 2012 by American Heart Association, Inc.