Ulka Sachdev1, Lena Vodovotz2, Julie Bitner3, Derek Barclay4, Ruben Zamora4, Jinling Yin4, Richard L Simmons4, Yoram Vodovotz4. 1. Division of Vascular Surgery, University of Pittsburgh, Pittsburgh, Pa; Department of Surgery, University of Pittsburgh, Pittsburgh, Pa. Electronic address: sachdevu2@upmc.edu. 2. School of Medicine, University of Pittsburgh, Pittsburgh, Pa. 3. Division of Vascular Surgery, University of Pittsburgh, Pittsburgh, Pa. 4. Department of Surgery, University of Pittsburgh, Pittsburgh, Pa.
Abstract
OBJECTIVE: Chronic venous insufficiency (CVI) affects 25 million adults in the United States. Little emphasis has been placed on inflammatory changes associated with CVI. We hypothesize that in patients with early to mid-stage benign varicose vein disease, differences in circulating inflammatory mediators will be manifested in blood draining the involved area vs circulating blood in control subjects. METHODS: Patients undergoing either endovenous ablation or sclerotherapy for Clinical, Etiology, Anatomy, and Pathophysiology clinical class 3 to 5 disease underwent phlebotomy from regional veins at the time of the procedure. The patient's age, gender, clinical class, duration of symptoms, presence of superficial truncal reflux by duplex ultrasound, and treatment modality were recorded. Plasma from patients and banked blood samples from healthy volunteers (HVs) were subjected to Luminex (EMD Millipore, Billerica, Mass) to evaluate the expression of an established panel of 20 inflammatory mediators. Mediator concentrations were compared between patients and HVs using Mann-Whitney U tests. Importantly, computational analysis allowed us to compare not only the panel of inflammatory mediators but also the inflammatory networks connecting these mediators to one another. Principal components were analyzed to assess network robustness in each group. RESULTS: CVI venous blood revealed significantly lower levels of monokine induced by γ interferon, soluble interleukin (IL) 2 receptor α chain, IL-4, IL-6, IL-7, tumor necrosis factor α, eotaxin, and granulocyte-macrophage colony-stimulating factor than blood from controls. Inflammatory networks were significantly less complex and less robust in the CVI patients compared with HVs. Based on principal component analysis, responses among HVs were more varied than those of CVI patients. CONCLUSIONS: We demonstrate that patients with CVI have significant differences not only in blood-borne inflammatory mediators but also in the interconnectedness of these mediators with one another and in their principal inflammatory characteristics. Results suggest hypoinflammation in chronic nonhealing changes in CVI. These novel findings, if validated in larger cohorts, may help predict the risk of disease progression or response to therapy in the future and may guide mechanistic studies on tissue responses to CVI.
OBJECTIVE:Chronic venous insufficiency (CVI) affects 25 million adults in the United States. Little emphasis has been placed on inflammatory changes associated with CVI. We hypothesize that in patients with early to mid-stage benign varicose vein disease, differences in circulating inflammatory mediators will be manifested in blood draining the involved area vs circulating blood in control subjects. METHODS:Patients undergoing either endovenous ablation or sclerotherapy for Clinical, Etiology, Anatomy, and Pathophysiology clinical class 3 to 5 disease underwent phlebotomy from regional veins at the time of the procedure. The patient's age, gender, clinical class, duration of symptoms, presence of superficial truncal reflux by duplex ultrasound, and treatment modality were recorded. Plasma from patients and banked blood samples from healthy volunteers (HVs) were subjected to Luminex (EMD Millipore, Billerica, Mass) to evaluate the expression of an established panel of 20 inflammatory mediators. Mediator concentrations were compared between patients and HVs using Mann-Whitney U tests. Importantly, computational analysis allowed us to compare not only the panel of inflammatory mediators but also the inflammatory networks connecting these mediators to one another. Principal components were analyzed to assess network robustness in each group. RESULTS: CVI venous blood revealed significantly lower levels of monokine induced by γ interferon, soluble interleukin (IL) 2 receptor α chain, IL-4, IL-6, IL-7, tumor necrosis factor α, eotaxin, and granulocyte-macrophage colony-stimulating factor than blood from controls. Inflammatory networks were significantly less complex and less robust in the CVI patients compared with HVs. Based on principal component analysis, responses among HVs were more varied than those of CVI patients. CONCLUSIONS: We demonstrate that patients with CVI have significant differences not only in blood-borne inflammatory mediators but also in the interconnectedness of these mediators with one another and in their principal inflammatory characteristics. Results suggest hypoinflammation in chronic nonhealing changes in CVI. These novel findings, if validated in larger cohorts, may help predict the risk of disease progression or response to therapy in the future and may guide mechanistic studies on tissue responses to CVI.
Authors: Asmita Chopra; Ruben Zamora; Yoram Vodovotz; Jacob C Hodges; Derek Barclay; Randall Brand; Richard L Simmons; Kenneth K Lee; Alessandro Paniccia; Pranav Murthy; Michael T Lotze; Brian A Boone; Amer H Zureikat Journal: J Immunother Date: 2021-06-01 Impact factor: 4.912
Authors: Lena Vodovotz; Ruben Zamora; Derek A Barclay; Yoram Vodovotz; Jinling Yin; Julie Bitner; John Florida; Efthymios D Avgerinos; Ulka Sachdev Journal: Ann Transl Med Date: 2021-11
Authors: Ewa A Burian; Lubna Sabah; Tonny Karlsmark; Klaus Kirketerp-Møller; Christine J Moffatt; Jacob P Thyssen; Magnus S Ågren Journal: Int J Mol Sci Date: 2022-06-10 Impact factor: 6.208