Role of Urotensin-2 in 5-Fluorouracil-Related Arterial Vasoconstriction in Cancer Patients

Abstract

Background: The aim of this study was to identify the possible relationship of 5-fluorouracil (5-FU)-related arterial vasoconstriction with urotensin-2 (UT-2), which has a high potential as an endogenic vasoconstrictor. Methods: We assigned the patients to 1 of 3 groups. Patients in group 1 received a bolus of 5-FU, those in group 2 a continuous infusion (CI) of 5-FU, and those in group 3 no 5-FU, which was also a control group. Pre- and post-treatment UT-2 levels and brachial arterial diameters were measured and recorded in all patients. Results: 132 patients were included in the study. Pre- and post-treatment brachial artery diameters were similar in all groups: in group 1 (3.28 ± 0.52 vs. 3.25 ± 0.44 mm, p = 0.740), in group 2 (3.57 ± 0.47 vs. 3.46 ± 0.45 mm, p = 0.441) and in the control group (3.51 ± 0.52 vs. 3.25 ± 0.44 mm, p = 0.818). Pre- and post-treatment UT-2 levels were significantly different in each group: in group 1 (39.5 ± 30.9 vs. 56.7 ± 27.1 ng/ml, p = 0.0001), in group 2 (37.7 ± 33.7 vs. 62.5 ± 37.7 ng/ml, p = 0.0001) and in the control group (52.9 ± 40.2 vs. 60.8 ± 40.7 ng/ml, p = 0.006). Conclusion: Our findings suggest that UT-2 has a high potential as a vasoconstrictor agent in our bodies and its level increases through a bolus or CI 5-FU. Increased UT-2 levels are likely to play a role in 5-FU-related cardiac toxicity pathogenesis.

Activated ROCK/Akt/eNOS and ET-1/ERK pathways in 5-fluorouracil-induced cardiotoxicity: modulation by simvastatin

“…Hence, based on the present work and the clinical data available hitherto, NT-proBNP might be a promising marker for 5-FU cardiotoxicity. Besides, arterial vasoconstriction induced by 5-FU has been amply reviewed 52,53 , which supports the boosting effect of 5-FU on the potent vasoconstrictor ET-1, and hence matches the findings of Porta et al 54 and pins down the theory of 5-FU-induced coronary vasospasm 55 . A positive correlation between ET-1 and NT-proBNP is plausible, since a synchronized elevation between the two markers was reported here and earlier 56 .…”

Incident Cardiovascular Diseases Among Survivors of High-Risk Stage II–III Colorectal Cancer: A Cluster-Wide Cohort Study

“…Mechanisms responsible for fluoropyrimidinerelated cardiotoxicity are multifactorial. 7,40 Fluoropyrimidine treatment can lead to endothelial damage, which can increase secretion of vasoconstrictors, 41,42 disturb production of nitric oxide, 43 activate apoptosis in endothelial cells and myocytes, 44,45 and trigger thrombosis due to platelet clumps and fibrin formations. 46 Endothelial dysfunction and primary smooth muscle dysfunction result in coronary artery spasm, which is an important mechanism implicated in myocardial ischemia and damage.…”

Cardiotoxicity of Fluoropyrimidines: Epidemiology, Mechanisms, Diagnosis, and Management

“…Based on preclinical studies, endothelial dysfunction should activate apoptosis and autophagy pathways in both endothelial cells and myocytes [ 85 , 86 ]. Another consequence of endothelial damage is an increased blood level of vasoconstrictors, such as endothelin-1 and urotensin-2, which was observed in 5-FU treated patients [ 87 , 88 ]. Severe endothelial damage, together with platelet accumulation and fibrin formation, was also observed in 5-FU-treated rabbits in scanning electron microscopy studies [ 89 ].…”