Dual role of fatty acid-binding protein 5 on endothelial cell fate: a potential link between lipid metabolism and angiogenic responses

Abstract

Fatty acid-binding proteins (FABP) are small molecular mass intracellular lipid chaperones that are expressed in a tissue-specific manner with some overlaps. FABP4 and FABP5 share ~55 % amino acid sequence homology and demonstrate synergistic effects in regulation of metabolic and inflammatory responses in adipocytes and macrophages. Recent studies have shown that FABP4 and FABP5 are also co-expressed in a subset of endothelial cells (EC). FABP4, which has a primarily microvascular distribution, enhances angiogenic responses of ECs, including proliferation, migration, and survival. However, the vascular expression of FABP5 has not been well characterized, and the role of FABP5 in regulation of angiogenic responses in ECs has not been studied to date. Herein we report that while FABP4 and FABP5 are co-expressed in microvascular ECs in several tissues, FABP5 expression is also detected in ECs of larger blood vessels. In contrast to FABP4, EC-FABP5 levels are not induced by VEGF-A or bFGF. FABP5 deficiency leads to a profound impairment in EC proliferation and chemotactic migration. These effects are recapitulated in an ex vivo assay of angiogenesis, the aortic ring assay. Interestingly, in contrast to FABP4-deficient ECs, FABP5-deficient ECs are significantly more resistant to apoptotic cell death. The effect of FABP5 on EC proliferation and survival is mediated, only in part, by PPARδ-dependent pathways. Collectively, these findings demonstrate that EC-FABP5, similar to EC-FABP4, promotes angiogenic responses under certain conditions, but it can also exert opposing effects on EC survival as compared to EC-FABP4. Thus, the balance between FABP4 and FABP5 in ECs may be important in regulation of angiogenic versus quiescent phenotypes in blood vessels.

Proteomic analysis of urinary extracellular vesicles from high Gleason score prostate cancer

“…Interestingly, patients with lymph node metastasis had higher levels of serum FABP5, as measured by ELISA 30 . FABP5 promotes the proliferation of endothelial cells 31 . The present study showed the high expression of FABP5 in EVs from patients with high GS prostate cancer.…”

LNMICC Promotes Nodal Metastasis of Cervical Cancer by Reprogramming Fatty Acid Metabolism

“…FABP5 is a small (15 kDa) member of the cytoplasmic FABP family and exhibits high affinity binding of long-chain FAs. There is now convincing evidence that FABP5 plays a crucial role in cancer progression, invasion and metastasis through the induction of EMT and the regulation of angiogenic responses [12,13]. However, it remains largely unknown how cervical cancer cells cope with the reprogramming of FA metabolism, thus resulting in LN metastasis.…”

Comparative global immune-related gene profiling of somatic cells, human pluripotent stem cells and their derivatives: implication for human lymphocyte proliferation

“… 26 Immunohistochemistry and immunofluorescence were performed on formalin-fixed, paraffin-embedded teratoma sections and differentiated stem cells as previously described. 27 Briefly, all primary antibody incubations were performed overnight at 4 °C. The primary antibodies were used at the following concentrations: mouse monoclonal anti-CD24 (Thermo), 1:10; mouse monoclonal anti-GATA3 (Thermo), 1:50; goat monoclonal anti-SOX17 (R&D System), 1:10; goat monoclonal anti-brachury (R&D System, Minneapolis, MN, USA), 1:10; rabbit monoclonal anti-beta III tubulin (ab18207, Abcam), 1:500.…”