Metabolic Reprogramming of Vascular Endothelial Cells: Basic Research and Clinical Applications

Abstract

Vascular endothelial cells (VECs) build a barrier separating the blood from the vascular wall. The vascular endothelium is the largest endocrine organ, and is well-known for its crucial role in the regulation of vascular function. The initial response to endothelial cell injury can lead to the activation of VECs. However, excessive activation leads to metabolic pathway disruption, VEC dysfunction, and angiogenesis. The pathways related to VEC metabolic reprogramming recently have been considered as key modulators of VEC function in processes such as angiogenesis, inflammation, and barrier maintenance. In this review, we focus on the changes of VEC metabolism under physiological and pathophysiological conditions.

Promising Strategies for Preserving Adult Endothelium Health and Reversing Its Dysfunction: From Liquid Biopsy to New Omics Technologies and Noninvasive Circulating Biomarkers

“…Consistent with these observations, the current evidence reports a close relationship between biochemical or structural injury, altered genesis, homeostasis, and function of the endothelium, and the onset and progression of pathological conditions correlated to inflammation, thrombosis, and atherosclerosis, as well as alterations in the vascular resistance and blood pressure [ 2 , 4 , 9 , 10 , 11 ]. Consequently, endothelial dysfunction is assumed as the axis of activation of all pathophysiological mechanisms and related disease pathways linked to excessive morbidity and mortality, such as hypertension, myocardial infarction, aneurysm, stroke, diabetes, metabolic syndrome, rheumatic diseases, renal failure, neurodegenerative diseases, cancer, and inflammatory diseases [ 2 , 4 , 5 , 8 , 9 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ] (see Figure 2 ). For instance, tumor neovascularization is characterized by a highly disordered vascular endothelium network and the generation of new blood vessels.…”

Advances in the therapeutic application and pharmacological properties of kinsenoside against inflammation and oxidative stress-induced disorders

“…Owing that KD acted as a negative mediator of PTP1B activity, it was possible that KD produced hypoglycemic effects by abrogating PTP1B activation in an anti-inflammationdependent manner (Wang et al, 2015). Once irritated by hyperglycemia, cellular oxidases become overactive and antioxidants are down-regulated, both of which induce vast ROS accumulation and provoke oxidative impairment of intracellular macromolecules, thereby resulting in endothelial dysfunction (Peng et al, 2021;Wautier and Wautier, 2022). Moreover, ROS overload is found to trigger the activation of cytosolic NF-κB and sequential translocation into the nucleus for transcribing pro-inflammatory factors like interleukins and MMPs, further damaging the lumen of vasculature.…”

Venous Wall of Patients with Chronic Venous Disease Exhibits a Glycolytic Phenotype

“…Metabolic changes can be one of the putative biological mechanisms implicated in the pathogenesis of CVeD [ 22 ]. Sustained inflammation, hypoxia and endothelial injury are associated with a metabolic reprogramming of the vascular wall [ 23 ]. Both endothelial and vascular smooth muscle cells strongly depend on glucose metabolism and glycolysis in physiological conditions [ 23 , 24 ], and likewise, an aberrant regulation of these processes appears to be critically involved in vascular disorders [ 25 , 26 ].…”

“…Sustained inflammation, hypoxia and endothelial injury are associated with a metabolic reprogramming of the vascular wall [ 23 ]. Both endothelial and vascular smooth muscle cells strongly depend on glucose metabolism and glycolysis in physiological conditions [ 23 , 24 ], and likewise, an aberrant regulation of these processes appears to be critically involved in vascular disorders [ 25 , 26 ]. Histological alterations in glycolysis markers in the placenta of women with CVeD has been recently demonstrated [ 27 ].…”