Cross-Talk Between Skeletal Muscle and Endothelial Cells in an Obesogenic Environment: Implications for Angiogenesis and Myogenesis

Obesity, defined as BMI ≥ 30 kg/m², is a major public health issue in the US, linked to increased risk for cardiovascular disease (CVD) and type 2 diabetes (T2DM). Marked by disrupted cellular communication and elevated non-esterified fatty acids and inflammatory cytokines, obesity contributes to dysfunction in vascular and skeletal muscle (SkM) systems, impacting glucose homeostasis and leading to endothelial and muscle impairments. Effective communication between endothelial cells (ECs) and SkM, facilitated by mechanisms such as extracellular vesicles (EVs), is critical for vascular health, glucose metabolism, and tissue repair. In obesity, however, this signaling is altered, leading to reduced angiogenic capacity and increased reactive oxygen species (ROS) production, perpetuating a cycle of inflammation and metabolic dysfunction.

The primary aim of my dissertation was to explore the bidirectional relationship and communication between skeletal muscle and endothelial cells in obesity. Chapter 1 discusses the physiology and pathology of obesity with a focus on cellular interactions between endothelial and skeletal muscle cells. In Chapter 2, we investigated cellular communication originating from obesity-induced skeletal muscle and its effect on endothelial cell angiogenesis. Our findings indicate that a 50/50 conditioned obesogenic media reduced HUVEC (human umbilical vein endothelial cells) proliferation and viability and increased ROS levels; however, no significant differences were observed after accounting for the vehicle control, suggesting that the BSA (bovine serum albumin) vehicle may have affected these outcomes. Chapter 3 examines the impact of obesity-induced HUVEC communication on skeletal muscle myogenesis. Obesogenic media reduced the MuSC (muscle satellite cells) fusion index compared to control, but no significant differences were found when vehicle control effects were considered. BSA, used as a vehicle control, may limit results due to its reduced nutrient profile compared to FBS (fetal bovine serum), potentially affecting nutrient availability and cellular response. Chapter 4 provides a review, summarizing the studies and discussing limitations and future directions for this research.