Angiogenesis in Adipose Tissue: The Interplay Between Adipose and Endothelial Cells

Abstract

Obesity is a worldwide health problem, and as its prevalence increases, so does the burden of obesity-associated co-morbidities like type 2 diabetes or cardiovascular diseases (CVDs). Adipose tissue (AT) is an endocrine organ embedded in a dense vascular network. AT regulates the production of hormones, angiogenic factors, and cytokines. During the development of obesity, AT expands through the increase in fat cell size (hypertrophy) and/or fat cell number (hyperplasia). The plasticity and expansion of AT is related to its angiogenic capacities. Angiogenesis is a tightly orchestrated process, which involves endothelial cell (EC) proliferation, migration, invasion, and new tube formation. The expansion of AT is accelerated by hypoxia, inflammation, and structural remodeling of blood vessels. The paracrine signaling regulates the functional link between ECs and adipocytes. Adipocytes can secrete both pro-angiogenic molecules, e.g., tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), or vascular endothelial growth factor (VEGF), and anti-angiogenic factors, e.g., serpins. If the pro-angiogenic molecules dominate, the angiogenesis is dysregulated and the endothelium becomes dysfunctional. However, if anti-angiogenic molecules are overexpressed relative to the angiogenic regulators, the angiogenesis is repressed, and AT becomes hypoxic. Furthermore, in the presence of chronic nutritional excess, endothelium loses its primary function and contributes to the inflammation and fibrosis of AT, which increases the risk for CVDs. This review discusses the current understanding of ECs function in AT, the cross-talk between adipose and ECs, and how obesity can lead to its dysfunction. Understanding the interplay of angiogenesis with AT can be an approach to therapy obesity and obesity-related diseases such as CVDs.

Adipocytes and Stromal Cells Regulate Brown Adipogenesis Through Secretory Factors During the Postnatal White-to-Brown Conversion of Adipose Tissue in Syrian Hamsters

“…Therefore, it is unknown which types of cells secrete the factors that regulate adipogenesis and exhibits activated BMP and MAPK pathways. Indeed, the factors highly expressed in SV cells include VEGF-D and nerve growth factor, which induce proliferation and differentiation of endothelial cells and neurons ( Chaldakov et al, 2009 ; Herold and Kalucka, 2020 ). BAT is highly vascularized and innervated with sympathetic nerves, both of which are indispensable to the thermogenic function of BAT ( Xue et al, 2009 ; Blaszkiewicz et al, 2019 ).…”

Nutritional Regulation of Mammary Tumor Microenvironment

“…Activation of angiogenesis is critical to ensure a sufficient supply of nutrients and oxygen to cells for healthy expansion. However, a balance between pro-angiogenic and antiangiogenic factors is necessary to prevent endothelial cell dysfunction (Herold and Kalucka, 2020). Obesity-related expansion of WAT is accompanied by endothelial dysfunction as there is an increase in the pro-angiogenic and pro-inflammatory stimulus.…”

Perirenal Adipose Tissue Inflammation: Novel Insights Linking Metabolic Dysfunction to Renal Diseases

“…Adipokines encompass a group of endocrine proteins synthesized and released by adipose tissues functioning as regulators of the immune system and metabolism including insulin sensitivity and energy balance ( 56 ). These properties of adipokines are linked to metabolic dysfunction, CVD, and type 2 diabetes mellitus pathogenesis ( 57 , 58 ). PRAT is highly active in adipokine synthesis as well as several pro-inflammatory cytokines ( 12 , 59 ).…”