Homocysteine Facilitates Prominent Polygonal Angiogenetic Networks of a Choroidal Capillary Sprouting Model

Abstract

Citation: Lee Y-J, Chiu C-C, Ke C-Y, Tien N, Lin P-K. Homocysteine facilitates prominent polygonal angiogenetic networks of a choroidal capillary sprouting model. Invest Ophthalmol Vis Sci. 2017;58:4332-4343. DOI: 10.1167/iovs.17-22308 PURPOSE. To investigate the effects of homocysteine on choroidal angiogenesis, we established an ex vivo choroidal sprouting explant model and examined the potential growth factors for angiogenesis.METHODS. Choroid fragments with retinal pigment epithelium were isolated from mouse and embedded in Matrigel. Homocysteine at different concentrations were added to the culture mediums. The choroidal explants were observed at different time points, and the total area of choroidal sprouting was measured and analyzed.RESULTS. Homocysteine evoked choroidal capillary sprouting by inducing capillary endothelial cell proliferation with pericyte formation and by facilitating polygonal angiogenetic networks. In some cases, vascular lumens were observed in the newly forming capillaries facilitated by homocysteine. The choroidal sprouting effect of homocysteine can only be observed at a certain range of homocysteine concentration, with 1-mM homocysteine exhibiting the most significantly increased choroidal sprouting areas. Isolectin overexpression was noted in the homocysteine-treated group. Possible growth factors for angiogenesis were detected through immunofluorescent staining, which demonstrated the overexpression of platelet-derived growth factor C and angiopoietin 1 in the homocysteine-treated preparations only. In these preparations, platelet-derived growth factor C was highly expressed in the tip cells of sprouting capillaries.CONCLUSIONS. We therefore conclude that platelet-derived growth factor C and angiopoietin 1 may play key roles in the choroid angiogenesis evoked by homocysteine.

Hyperhomocysteinemia Causes Chorioretinal Angiogenesis with Placental Growth Factor Upregulation

“…We previously reported that plasma hcy levels were significantly higher in patients with PCV than in those without PCV 29 , and we found that choroidal angiogenesis was facilitated by hcy in a choroidal capillary sprouting model 30 . Therefore, we assumed that hyperhomocysteinemia may play a role in type I CNV development, including PCV, possibly via an atherosclerosis pathway.…”

Premenopausal breast cancer: potential clinical utility of a multi-omics based machine learning approach for patient stratification

“…Consequently, both significantly increased and/or decreased levels of Cat are strongly indicative for imbalanced production of ROS [39]. -Although its role in BC pathology is inconsistent in the literature, homocysteine (Hcy) has been reported as a proliferation [40] and angiogenesis stimulating metabolite [41]. Moreover, Hcy induces metalloproteinase-2 in a dose-dependent manner [42], which is a prognostic biomarker for tumour aggressiveness and poor outcome in BC patients [43].…”