[AVX Seminar] Tackling metabesity. Is angiogenesis a missed link?

Title: Tackling metabesity. Is angiogenesis a missed link?

Speaker: Raquel Soares

Affiliation: FMUP, I3S - Universidade do Porto

Metabesity is a cluster of major chronic diseases that have common metabolic roots. These include obesity, diabetes and several types of cancer. In fact, the worldwide prevalence of obesity, diabetes and cancer is huge and still increasing, despite the recent advances in diagnostic tools and public awareness regarding disease symptoms. These disorders share a common feature. Accordingly, angiogenesis, the proliferation of new blood vessels from pre-existing ones, is always imbalanced in these pathological conditions. Therefore, our group has concentrated efforts in understanding the role of angiogenesis in this constellation of diseases.

Using type 1 and type 2 diabetic animal models, we were able to show that angiogenesis accompany metabolic disturbances in specific organs, such as heart and kidney. In agreement, vascular endothelial cells (ECs) from kidney diabetic mice overexpress angiogenic markers, namely VEGF signaling pathway, and glycolysis activators, whereas the opposite is observed in ECs from diabetic hearts.

Interestingly, obesity influences cancer development and progression. Breast and pancreatic cancer aggressiveness is higher in obese animals. However, inhibiting angiogenesis in obese animals reduced cancer growth, body weight and improved anti-tumor immunity. In another cancer model, melanoma, an adipocyte secretome induces melanoma cells dedifferentiation into vessel-like structures in vitro. This process, designated as vascular mimicry was further confirmed in an in vivo model.

Altogether, our findings confirm that angiogenesis imbalance is a common feature in metabesity. Targeting angiogenesis might be a therapeutic strategy against these diseases that are major burdens to the health care system.