Endothelial Dysfunction and Metabolic Reprogramming in Cardiovascular Diseases

Endothelial cells regulate hemodynamics, inflammation, and vascular barrier integrity, thereby playing a central role in vascular homeostasis. Pathological conditions, including hypertension, hyperglycemia, and hyperlipidemia, induce metabolic reprogramming in these cells, altering the balance among glycolysis, fatty acid oxidation, and amino acid metabolism. This reprogramming drives endothelial dysfunction, characterized by reduced nitric oxide (NO) levels, increased inflammation and oxidative stress, and a weakened vascular barrier, thereby accelerating the progression of atherosclerosis, myocardial infarction, calcific aortic valve disease, and aortic aneurysms. Altered metabolites, such as lactate and acetyl-CoA, further exacerbate injury by modulating epigenetic changes and cell signaling. Endothelial metabolism has emerged as a promising therapeutic target for cardiovascular diseases. Natural compounds such as resveratrol, quercetin, and curcumin enhance NO production and reduce oxidative stress. Traditional Chinese medicine formulations (e.g., Qili Qiangxin and Tongxinluo capsules) help regulate glucose and lipid metabolism, thereby mitigating mitochondrial dysfunction and inflammation. Synthetic drugs, including metformin, sodium-glucose transporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor (GLP-1R) agonists, and experimental agents such as I-152, protect vessels by restoring metabolic homeostasis and endothelial function. Future research integrating multi-omics technologies and artificial intelligence is expected to enable real-time metabolic monitoring and precision interventions. Emerging delivery systems, such as exosome-based approaches and stem cell therapies, offer additional therapeutic potential. A deeper understanding of endothelial metabolic reprogramming will provide novel targets for preventing and treating cardiovascular diseases, thereby advancing precision medicine.