Tag Archives: angiostatin
Therapeutic potential of topical autologous angiostatin application in managing tuberculosis-related corneal injury: a case report
N. Greben1*, I. Gavryliak1, V. Bilous2,
V. Korsa2, A. Tykhomyrov2
1Department of Ophthalmology, Bogomolets National Medical University, Kyiv, Ukraine;
2Department of Enzyme Chemistry and Biochemistry,
Palladin Institute of Biochemistry, Kyiv, Ukraine;
*e-mail: nkgreden@ukr.net
Received: 03 June 2025; Revised: 17 September 2025;
Accepted: 28 November 2025; Available on-line: 29 December 2025
Ocular tuberculosis (TB) is a vision-threatening condition that frequently manifests as corneal neovascularization and stromal keratitis, which triggers a cascade of inflammatory and hypoxia-driven responses. Conventional therapeutic approaches, including corticosteroids and antimicrobial agents, often fail to halt disease progression. Here, we report a case of a 50-year-old patient diagnosed with TB-associated keratitis, unresponsive to standard treatment. The aim of the study was to evaluate the effectiveness of the alternative therapeutic strategy involving topical administration of angiostatin, a natural anti-angiogenic polypeptide derived from the autologous plasminogen. Solution of angiostatin fragment containing the first three kringle domains (K1-3) was applied in a two doses of eye drops (~15 μg per administration) five times daily for 2 months, with a cumulative exposure of approximately 4.5 mg. Treatment efficacy was monitored using both standard ophthalmologic assessments and non-invasive biochemical indicators such as the levels of hypoxia-inducible factor HIF-1α, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP-9), fibrinogen/fibrin (Fg/Fb) and lactoferrin measured the in tear fluid across treatment time points (Day 0, 14, and 61) using Western blot analysis. The high intensity of HIF-1 α, VEGF and MMP-9 expression, Fg/Fb accumulation and the presence of low-molecular-weight fragments of lactoferrin were detected in the tear fluid prior to the treatment. Following angiostatin therapy, the patient exhibited marked regression of corneal neovascularization and restoration of corneal transparency, complemented with normalization of HIF-1α, VEGF, and MMP-9 levels, reduced Fg/Fb accumulation and the presence of intact lactoferrin in the tear fluid. The data obtained demonstrated a multifactorial mechanism of angiostatin action that extends beyond classical anti-angiogenic pathways. The convergence of clinical and molecular indicators of recovery underscores the potential of angiostatin application as a safe and effective therapeutic alternative for managing corneal complications in ocular TB, particularly in cases resistant to conventional treatment.
Citicoline affects serum angiostatin and neurospecific protein levels in patients with atrial fibrillation and ischemic stroke
A. A. Tykhomyrov1, Yu. S. Kushnir2, V. S. Nedzvetsky3,
T. V. Grinenko1, O. V. Kuryata2
1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
2State Establishment “Dnipropetrovsk Medical Academy of Health Ministry of Ukraine”, Dnipro;
3Bingöl University, Bingöl, Turkey;
e-mail: artem_tykhomyrov@ukr.net
Received: 22 May 2019; Accepted: 13 August 2019
Ischemic stroke is considered as one of the most frequent and severe complications of atrial fibrillation. The present study was undertaken to examine whether post-insult treatment with cytidine diphosphate-choline (CDP-choline, or citicoline) affects serum levels of the angiogenesis inhibitor angiostatin and neurospecific proteins as markers of brain damage in patients with cerebral ischemia associated with atrial fibrillation. Thirty-three patients with a diagnosis of acute ischemic stroke received citicoline sodium by intravenous infusions (1,000 mg daily for 14 days) in addition to the standard treatment (basic group). Twenty-five patients with the same pathologies, who received only standard therapy, were enrolled in the study as a control group. Serum content of angiostatin and neurospecific proteins, namely neurofilament heavy subunit (NF-H) and glial fibrillary acidic protein (GFAP), was measured by immunoblotting at the basal level and after the treatment. Citicoline treatment caused significant decreases in serum levels of angiostatin (by 40% vs. basal level, P < 0.05), GFAP (by 61%, P < 0.01), and the NF-H subunit (by 19%, P < 0.05) and had no effect on the serum albumin content. In contrast, there were no statistically significant differences between baseline levels of the studied protein markers and their content after the treatment period in the control group. These findings indicate for the first time that CDP-choline protects both astrocytes and neurons and improves angiogenic capacity through down-regulation of angiostatin in post-ischemic patients with atrial fibrillation after acute ischemic stroke. Further studies are needed to test associations between serum levels of these biomarkers, clinical outcomes, and treatment efficacy of stroke.