Enhanced oxidative stress and platelet activation in patients with Cushing's syndrome

Abstract

Summary Objective Cushing Syndrome (CS) is implicated by increased cardiovascular risk (CVR) leading to increased morbidity and mortality. Oxidative stress (OS) and platelet activation (PA) are associated with increased CVR. However, scarce data of OS in CS exist. Our objective was to determine the oxidant–antioxidant balance in CS. Design Fourteen patients with CS at diagnosis and fourteen healthy subjects (NS) were evaluated OS by measuring plasma 15‐F2t‐Isoprostane (15‐F2t‐IsoP), PA by thromboxaneB2 levels (TXB2), and antioxidant reserve measuring total antioxidant capacity (TAC) and serum vitamin E. Results 15‐F2t‐IsoP and TXB2 levels were significantly higher (P < 0·01) in CS, while vitamin E levels were higher in NS (P < 0·03). 15‐F2t‐IsoP levels were significantly higher (P < 0·01) in complicated vs not‐complicated CS and NS and significantly higher (P < 0·03) in CS not‐complicated vs NS. TXB2 levels were significantly reduced (P < 0·03) in NS vs complicated and not‐complicated CS. A negative correlation between Vitamin E and UFC was observed in CS (P < 0·05 r = −0·497). TXB2 correlated with glucose, HbA1c and T‐score (P < 0·05 r = 0·512, P < 0·03 r = 0·527 and P < 0·01 r = 0·783, respectively) and HDL (P < 0·01 r = −0·651). 15‐F2t‐IsoP correlated with triglicerides, HbA1c and diastolic pressure (P < 0·01 r = 0·650, P < 0·03 r = 0·571 and P < 0·05 r = 0·498, respectively) and HDL (P < 0·03 r = −0·594). Conclusions This study emphasizes the major role of OS in CS. As our findings demonstrated that enhanced OS and PA take place in this rare metabolic disorder which is associated with increased CVR, it could be suggested that these biochemical alterations can further contribute in the pathogenesis of atherosclerosis, increased CVR and mortality in CS.

Platelet Hyperactivity inTNFSF14/LIGHTKnockout Mouse Model of Impaired Healing

“…Moreover, reactive oxygen species frequently observed in impaired and chronic wounds have increasingly been shown to be major players in the activation of platelets and to cause thrombus formation. 37,38 In conclusion, this work shows a novel function for TNFSF14/LIGHT during wound healing; in the absence of this molecule from the cell surface, platelets show higher levels of aggregation, potentially contributing to rapid thrombosis during the early stages of healing, which might contribute to impaired healing by reducing the ability of the blood vessels to transport nutrients and oxygen as well as other serum molecules needed for proper healing of the wound tissue. Furthermore, this environment can lead to cell death, contributing to impaired healing.…”

MECHANISMS IN ENDOCRINOLOGY: The spectrum of haemostatic abnormalities in glucocorticoid excess and defect

“…By contrast, in 2014, Karamouzis et al (21) described enhanced platelet aggregation in patients with CS: thromboxane A2 (TXA2) has been shown to cause platelet release, activation and accumulation and to exert potent vasoconstrictive effects (22); TXB2, which represents a reliable indicator of TXA2 biosynthesis, was significantly higher (P!0.01) in patients affected by CS (21). It therefore seems likely that there is a minor, albeit significant, increase in platelet functionality in CS.…”

“…A recent study showed that SGK1 expression is stimulated by a wide variety of hormones, including GCs and mineralocorticoids (20). A previous systematic review failed to show significantly altered platelet aggregation in patients with CS, although the studies reviewed were of low quality (21).…”

Metabolic comorbidities in Cushing's syndrome

“…Vitamin E levels, a suggested marker of the antioxidant status, were significantly lower in CS patients compared to controls. These findings would suggest that excess GCs induce pro-oxidative processes which, in combination with the metabolic comorbidities, lead to a vicious loop of worsening oxidant-antioxidant balance and increased cardiovascular morbidity and mortality (170).…”