Reduction expression of thrombomodulin and endothelial cell nitric oxide synthase in dermatomyositis

Abstract

Dermatomyositis (DM) is a systemic microvasculitis predominantly involving the capillaries. We investigated the expression of thrombomodulin (TM) and endothelial cell nitric oxide synthase (eNOS) in microvessels of DM patients. Twelve patients with acute or subacute onset of proximal muscle weakness and erythematous rash over their faces and shoulders were included in this study. Serum creatine phosphokinase was elevated in almost all patients. Electromyograph showed a myopathic pattern in all patients. Muscle biopsies were performed in all patients and 10 non-DM controls and studied with histological, enzyme histochemical and immunohistochemical staining. von Willebrand factor, TM and eNOS antibodies were used as the primary antibodies. Perifascicular degeneration and inflammatory cell infiltration in the perimysium were noted in almost all patients. Non-special esterase staining was markedly positive in capillary and microvascular endothelium. Marked reduction in TM and eNOS staining was noted in DM patients in perimysium microvessels and perifascicular area capillaries. Vascular lesions in DM were not only limited to capillaries. The low expression of TM and eNOS in microvessels suggests the anticoagulation and vasodilation functions of vascular endothelium is reduced. DM is an inflammatory vascular endothelial disease.

Role of endothelial nitric oxide synthase in remote ischemic preconditioning of the mouse liver

“…The expression of eNOS within the liver was observed in hepatocytes and the vascular endothelium; these results are congruent with those reported previously 9, 10. In hindlimb skeletal muscle sections, eNOS expression was apparent in the myocytes and vascular endothelium; these cellular structures have also been reported to express eNOS 27, 28. It is likely that both hepatic eNOS and preconditioned hindlimb skeletal muscle eNOS contribute to the protection of RIPC.…”

Altered expression of eNOS, prostacyclin synthase, prostaglandin G/H synthase, and thromboxane synthase in porcine aortic endothelial cells after exposure to human serum—relevance to xenotransplantation

“…Activation of vascular ECs promotes thrombosis by the simultaneous induction of procoagulant activity and the suppression of anticoagulant properties. It has long been demonstrated that heparan sulfate (Platt et al, ), thrombomodulin (Shen et al, ), CD39 (Robson et al, ), and CD73 (Khalpey et al, ,) are rapidly lost from the surface of ECs after activation by proinflammatory cytokines or xenogeneic blood. Because excessive platelet activation and thrombotic microangiopathy have been recognized as important characteristics in pig‐to‐primate xenotransplantation models, we suggest that the vascular endothelium‐derived inhibitory mechanisms that regulate platelet activity may be impaired after EC activation.…”