| Autor: |
Katrina M. Mirabito Colafella, Daan C.H. van Dorst, Rugina I. Neuman, Leni van Doorn, Karla Bianca Neves, Augusto C. Montezano, Ingrid M. Garrelds, Richard van Veghel, René de Vries, Estrellita Uijl, Marian C. Clahsen-van Groningen, Hans J. Baelde, Anton H. van den Meiracker, Rhian M. Touyz, Willy Visser, A.H. Jan Danser, Jorie Versmissen |
| Přispěvatelé: |
Internal Medicine, Rehabilitation Medicine, Cardiology, Pathology |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Clinical Science, 136(9), 675-694. Portland Press, Ltd. |
| ISSN: |
0143-5221 |
| Popis: |
Vascular endothelial growth factor antagonism with angiogenesis inhibitors in cancer patients induces a ‘preeclampsia-like’ syndrome including hypertension, proteinuria and elevated endothelin (ET)-1. Cyclo-oxygenase (COX) inhibition with aspirin is known to prevent the onset of preeclampsia in high-risk patients. In the present study, we hypothesised that treatment with aspirin would prevent the development of angiogenesis inhibitor-induced hypertension and kidney damage. Our aims were to compare the effects of low-dose (COX-1 inhibition) and high-dose (dual COX-1 and COX-2 inhibition) aspirin on blood pressure, vascular function, oxidative stress, ET-1 and prostanoid levels and kidney damage during angiogenesis-inhibitor therapy in rodents. To this end, Wistar Kyoto rats were treated with vehicle, angiogenesis inhibitor (sunitinib) alone or in combination with low- or high-dose aspirin for 8 days (n=5–7/group). Our results demonstrated that prostacyclin (PGI2) and ET-1 were increased during angiogenesis-inhibitor therapy, while thromboxane (TXA2) was unchanged. Both low- and high-dose aspirin blunted angiogenesis inhibitor-induced hypertension and vascular superoxide production to a similar extent, whereas only high-dose aspirin prevented albuminuria. While circulating TXA2 and prostaglandin F2α levels were reduced by both low- and high-dose aspirin, circulating and urinary levels PGI2 were only reduced by high-dose aspirin. Lastly, treatment with aspirin did not significantly affect ET-1 or vascular function. Collectively our findings suggest that prostanoids contribute to the development of angiogenesis inhibitor-induced hypertension and renal damage and that targeting the prostanoid pathway could be an effective strategy to mitigate the unwanted cardiovascular and renal toxicities associated with angiogenesis inhibitors. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
