Apolipoprotein A1 suppresses the hypoxia-induced angiogenesis of human retinal endothelial cells by targeting PlGF

Abstract

AIM: To investigate the anti-angiogenic effect of apolipoprotein A1 (apoA1) on primary human retinal vascular endothelial cells (HRECs) and explore the possible mechanism. METHODS: The primary HRECs were transfected with apoA1-GFP recombinant lentiviral and were compared with cells undergoing transfection with empty lentiviral vectors. Hypoxia chambers were used to simulate the anoxic environment of cells under pathological condition. The concentrations of secreted vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) were measured by enzyme-linked immunosorbent assay (ELISA). Cell migration ability was detected by wound healing assay. The sprouting of HRECs was determined by tube formation assay. The protein levels of extracellular signal regulated kinase 1/2 (ERK1/2) and phosphorylated ERK1/2 (p-ERK1/2) were measured by Western blot. RESULTS: Overexpressed apoA1 in hypoxia-induced HRECs significantly suppressed PlGF (0.67±0.10 folds, P=0.007). Overexpressed apoA1 also attenuated hypoxia-induced cell migration (0.32±0.11 folds, P<0.0001), tube formation (0.66±0.01 folds, P<0.0001) and the phosphorylation levels of ERK (0.6±0.11 folds, P=0.025). Pretreatment of mitogen-activated protein kinase kinase (MEK) inhibitor (U0126) further reduced the PlGF and angiogenesis in hypoxia-induced HRECs. CONCLUSION: ApoA1 inhibits the angiogenesis at least in part by inactivating ERK1/2 in hypoxia-induced HRECs. Moreover, apoA1 suppresses the PlGF expression, which selectively associated with pathological angiogenesis.

Analyzing secretory proteins in human dermal fibroblast‐conditioned medium for angiogenesis: A bioinformatic approach

“…Hemoglobin subunit α, located at the myoendothelial junction of vessels, regulates endothelial nitric oxide synthase activity and nitric oxide diffusion 55 . Apolipoprotein A1 exhibits anti‐angiogenic activity by inactivating extracellular signal‐regulated kinase 1/2 in hypoxic tissue environments 56 . It also suppresses placental growth factor (PlGF), associated with pathological angiogenesis 56 .…”

“… 55 Apolipoprotein A1 exhibits anti‐angiogenic activity by inactivating extracellular signal‐regulated kinase 1/2 in hypoxic tissue environments. 56 It also suppresses placental growth factor (PlGF), associated with pathological angiogenesis. 56 Apolipoprotein D similarly demonstrates anti‐angiogenic activity and plays a role in axon regeneration and remyelination for functional recovery of peripheral nerve integrity.…”

“… 56 It also suppresses placental growth factor (PlGF), associated with pathological angiogenesis. 56 Apolipoprotein D similarly demonstrates anti‐angiogenic activity and plays a role in axon regeneration and remyelination for functional recovery of peripheral nerve integrity. 57 …”

“…56 It also suppresses placental growth factor (PlGF), associated with pathological angiogenesis. 56 Apolipoprotein D similarly demonstrates anti-angiogenic activity and plays a role in axon regeneration and remyelination for functional recovery of peripheral nerve integrity. 57 In DFCM, chloride intracellular channel protein 4 plays a crucial role in acidifying vacuoles during angiogenesis, facilitating endothelial cell tubulogenesis.…”

Distinguishing the impact of distinct obstructive sleep apnea syndrome (OSAS) and obesity related factors on human monocyte subsets

“…Apo1 has been suggested as promising novel biomarker for diagnosis of coronary artery disease 52 and it has been shown that ApoA1 is associated with pathological angiogenesis in hypoxia-induced human retinal vascular endothelial cells by inhibiting ERK1/2 signaling 53 .…”