Tag Archives: MMP-9
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.
Circulating levels of potential markers of ischemic stroke in patients with the different forms of atrial fibrillation and chronic heart failure
A. O. Tykhomyrov1*, O. Yu. Sirenko2, O. V. Kuryata2
1Department of Enzyme Chemistry and Biochemistry,
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv, Ukraine;
2Department of Internal Medicine 2, Phthisiology,
Occupational Diseases and Clinical Immunology, Dnipro State Medical University, Dnipro, Ukraine;
*e-mail: artem_tykhomyrov@ukr.net
Received: 19 January 2024; Revised: 13 March 2024;
Accepted: 17 March 2024; Available on-line: 30 April 2024
Atrial fibrillation (AF) is the most common abnormal type of heart rhythm (cardiac arrhythmia), which is considered the leading cause of stroke. There have been limited studies on the prognostic markers for atrial disease and AF-associated ischemic stroke, despite the high demand for this procedure in daily clinical practice to monitor disease course and assess risk of stroke in patients with AF and chronic heart failure (CHF). Thus, the aim of the present study was to evaluate the levels of serum biomarkers related to ischemic stroke in CHF patients with the different forms of AF. Forty-six patients with various types of AF (paroxysmal, persistent and permanent) with or without ischemic stroke were enrolled in the study, 36 clinically healthy donors served as a control. The levels of inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF) and angiostatins (AS) were evaluated by western blot analysis in the serum. The levels of active matrix metalloproteinases (MMPs) were analysed by gelatin zymography. Elevated levels of iNOS were shown in patients with all AF forms as compared with control, but iNOS levels in post-ischemic patients were significantly higher than that in paroxysmal AF individuals. However, the levels of VEGF and AS did not differ from the baseline value in patients with paroxysmal AF, while dramatic increase of their contents was shown in post-stroke patients with persistent and permanent types of AF. Elevated active MMP-9 levels were shown to be associated with the diagnosis of all AF forms, regardless of the occurrence of stroke. Taken together, our findings demonstrate that tested proteins can be considered as valuable biomarkers of AF forms transformation and potentially useful for ischemic stroke risk stratification in patients with AF and CHF. Observed changes in regulatory protein levels may expand our understanding of pathological roles of endothelial function dysregulation, disrupted angiogenesis balance and abnormal tissue remodeling in AF and associated ischemic events.
Multiple effects of angiostatins in injured cornea
V. L. Bilous*, A. O. Tykhomyrov
Department of Enzyme Chemistry and Biochemistry, Palladin Institute of Biochemistry,
National Academy of Sciences of Ukraine, Kyiv;
*e-mail: basil.bilous@gmail.com
Received: 07 October 2023; Revised: 01 November 2023;
Accepted: 01 February 2024; Available on-line: 26 February 2024
Prolonged inflammation and excessive neovascularization of the cornea due to severe injury can impair optical clarity and lead to vision impairment. Plasminogen kringle (K) fragments, known as angiostatins (AS), play a well-established role as inhibitors of neovascularization by suppressing pro-angiogenic signaling. However, AS effects in the cornea, beyond inhibiting the angiogenesis, are still unexplored. In this study, we estimate the protective effect of two AS variants (K1-3 and K5) against alkali burn injury induced in rabbit and rat corneas. AS K1-3 in the single doses of 0.075 or 0.75 μg (0.1 or 1.0 μM, respectively) or 0.3 μg of AS K5 (1.0 μM) were applied locally as eye drops daily for 14 days after the injury. A significant regression of corneal vessels in-growth in injured eyes treated with AS was revealed. Western blot analysis of corneal tissue lysates revealed that injury-induced overexpression of protein markers of hypoxia (HIF-1α), angiogenesis (VEGF), tissue remodeling and fibrosis (MMP-9), autophagy (beclin-1) and endoplasmic reticulum stress (GRP-78) was significantly reduced under AS treatment. Besides, the level of tight junctions protein ZO-1 was shown to be up-regulated after the treatment of the damaged cornea with AS K1-3. Summarizing, our study uncovered novel biological functions of the kringle-containing plasminogen fragments indicating its beneficial effects during corneal healing in the experimental model of alkali burn. The data obtained can be helpful for the development of novel efficient formulations to manage complications of ocular surface injuries.