Abstract

Endothelial dysfunction (ED) is characterized by an imbalance between vasodilatory and vasoconstrictive factors, leading to impaired vascular tone, thrombosis, and inflammation. These processes are critical in the development of cardiovascular diseases (CVDs) such as atherosclerosis, hypertension and ischemia/reperfusion injury (IRI). Reduced nitric oxide (NO) production and increased oxidative stress are key contributors to ED. Aging further exacerbates ED through mitochondrial dysfunction and increased oxidative/nitrosative stress, heightening CVD risk. Antioxidant systems like superoxide-dismutase (SOD), glutathione-peroxidase (GPx), and thioredoxin/thioredoxin-reductase (Trx/TXNRD) pathways protect against oxidative stress. However, their reduced activity promotes ED, atherosclerosis, and vulnerability to IRI. Metabolic syndrome, comprising insulin resistance, obesity, and hypertension, is often accompanied by ED. Specifically, hyperglycemia worsens endothelial damage by promoting oxidative stress and inflammation. Obesity leads to chronic inflammation and changes in perivascular adipose tissue, while hypertension is associated with an increase in oxidative stress. The NLRP3 inflammasome plays a significant role in ED, being triggered by factors such as reactive oxygen and nitrogen species, ischemia, and high glucose, which contribute to inflammation, endothelial injury, and exacerbation of IRI. Treatments, such as N-acetyl-L-cysteine, SGLT2 or NLRP3 inhibitors, show promise in improving endothelial function. Yet the complexity of ED suggests that multi-targeted therapies addressing oxidative stress, inflammation, and metabolic disturbances are essential for managing CVDs associated with metabolic syndrome.

MeSH

Hypertension, Cysteine, Stress, Physiological, Cardiovascular Diseases, Inflammasomes, Oxidative Stress, Thioredoxins, Reperfusion Injury, Atherosclerosis, Therapeutics, Ischemia, Metabolic Syndrome

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