Endothelial Dysfunction: Redox Imbalance, NLRP3 Inflammasome, and Inflammatory Responses in Cardiovascular Diseases
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 an...
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MDPI AG
2025-02-01
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| author | Claudia Penna Pasquale Pagliaro |
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| description | 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. |
| format | Article |
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| institution | OA Journals |
| issn | 2076-3921 |
| language | English |
| publishDate | 2025-02-01 |
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| spelling | doaj-art-a458ce6ecb2b4ababf84601d58e81b0d2025-08-20T02:11:17ZengMDPI AGAntioxidants2076-39212025-02-0114325610.3390/antiox14030256Endothelial Dysfunction: Redox Imbalance, NLRP3 Inflammasome, and Inflammatory Responses in Cardiovascular DiseasesClaudia Penna0Pasquale Pagliaro1Department of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, ItalyDepartment of Clinical and Biological Sciences, University of Turin, 10043 Orbassano, ItalyEndothelial 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.https://www.mdpi.com/2076-3921/14/3/256nitric oxideoxidative stressNLRP3 inflammasomeantioxidant treatmentsmetabolic syndromeischemia/reperfusion injury |
| spellingShingle | Claudia Penna Pasquale Pagliaro Endothelial Dysfunction: Redox Imbalance, NLRP3 Inflammasome, and Inflammatory Responses in Cardiovascular Diseases Antioxidants nitric oxide oxidative stress NLRP3 inflammasome antioxidant treatments metabolic syndrome ischemia/reperfusion injury |
| title | Endothelial Dysfunction: Redox Imbalance, NLRP3 Inflammasome, and Inflammatory Responses in Cardiovascular Diseases |
| title_full | Endothelial Dysfunction: Redox Imbalance, NLRP3 Inflammasome, and Inflammatory Responses in Cardiovascular Diseases |
| title_fullStr | Endothelial Dysfunction: Redox Imbalance, NLRP3 Inflammasome, and Inflammatory Responses in Cardiovascular Diseases |
| title_full_unstemmed | Endothelial Dysfunction: Redox Imbalance, NLRP3 Inflammasome, and Inflammatory Responses in Cardiovascular Diseases |
| title_short | Endothelial Dysfunction: Redox Imbalance, NLRP3 Inflammasome, and Inflammatory Responses in Cardiovascular Diseases |
| title_sort | endothelial dysfunction redox imbalance nlrp3 inflammasome and inflammatory responses in cardiovascular diseases |
| topic | nitric oxide oxidative stress NLRP3 inflammasome antioxidant treatments metabolic syndrome ischemia/reperfusion injury |
| url | https://www.mdpi.com/2076-3921/14/3/256 |
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