Kallistatin is an endogenous protein that exerts pleiotropic effects, including vasodilation and inhibition of angiogenesis, inflammation, oxidative stress, apoptosis, fibrosis, and tumor progression. Through its two functional domains – an active site and a heparin-binding site – kallistatin regulates differential signaling pathways and a wide spectrum of biological functions. Kallistatin's active site is key for inhibiting tissue kallikrein activity, and stimulating the expression of endothelial nitric oxide synthase (eNOS), sirtuin 1 (SIRT1) and suppressor of cytokine signaling 3 (SOCS3). Kallistatin via its heparin-binding site blocks signaling pathways mediated by growth factors and cytokines, such as vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), high mobility group box-1 (HMGB1), Wnt, transforming growth factor-β (TGF-β), and epidermal growth factor (EGF). Kallistatin gene or protein delivery protects against the pathogenesis of hypertension, heart and kidney damage, arthritis, sepsis, influenza virus infection, tumor growth and metastasis in animal models. Conversely, depletion of endogenous kallistatin by neutralizing antibody injection exacerbates cardiovascular and renal injury in hypertensive rats. Kallistatin levels are markedly reduced in rodents with hypertension, sepsis, streptozotocin-induced diabetes, and cardiac and renal injury. Kallistatin levels are also diminished in patients with liver disease, septic syndrome, diabetic retinopathy, severe pneumonia, inflammatory bowel disease, and obesity, prostate and colon cancer. Therefore, circulating kallistatin levels may serve as a new biomarker for human diseases. This review summarizes kallistatin's protective roles and mechanisms in vascular and organ injury, and highlights the therapeutic potential of kallistatin for multiple disease states.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.116.07861 | DOI Listing |
Surg Infect (Larchmt)
November 2024
Department of Obstetrics and Gynecology, Antalya Training and Research Hospital, Antalya, Turkey.
Gut
November 2024
Laboratory of Translational Gastroenterology, GIGA-institute, Liège University, Liège, Belgium.
Objective: In patients with Crohn's disease (CD) on combination therapy (infliximab and immunosuppressant) and stopping infliximab (cohort from the study of infliximab diSconTinuation in CrOhn's disease patients in stable Remission on combined therapy with Immunosuppressors (STORI)), the risk of short-term (≤6 months) and mid/long-term relapse (>6 months) was associated with distinct blood protein profiles. Our aim was to test the external validity of this finding in the SPARE cohort (A proSpective Randomized Controlled Trial comParing infliximAb-antimetabolites Combination Therapy to Anti-metabolites monotheRapy and Infliximab monothErapy in Crohn's Disease Patients in Sustained Steroid-free Remission on Combination Therapy).
Design: In SPARE, patients with CD in sustained steroid-free clinical remission and on combination therapy were randomly allocated to three arms: continuing combination therapy, stopping infliximab or stopping immunosuppressant.
Am J Reprod Immunol
August 2024
Departments of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
Am J Reprod Immunol
July 2024
Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
Problem: To explore the clinical utility of nine inflammatory immune-, adhesion-, and extracellular matrix-related mediators in the plasma for predicting intraamniotic inflammation and/or microbial invasion of the amniotic cavity (IAI/MIAC) and composite neonatal morbidity and/or mortality (CNMM) in women with preterm premature rupture of membranes (PPROM) when used alone or in combination with conventional blood-, ultrasound-, and clinical-based factors.
Methods Of Study: This retrospective cohort comprised 173 singleton pregnant women with PPROM (24 + 0 - 33 + 6 weeks), who underwent amniocentesis. Amniotic fluid was cultured for microorganisms and assayed for IL-6 levels.
Diagnostics (Basel)
July 2024
Faculty of Medicine, Department of Gynecology and Obstetrics, Kafkas University, Kars 36000, Turkey.
Background: Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder with significant metabolic implications, including an increased risk of cardiovascular diseases and diabetes. Kallistatin, a serine proteinase inhibitor with anti-inflammatory and antioxidative properties, has been identified as a potential biomarker for PCOS due to its role in modulating inflammation and oxidative stress.
Methods: This prospective cohort study was conducted at a university hospital's gynecology clinic.
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