Hirudin prevents vascular endothelial cell apoptosis and permeability enhancement induced by the serum from rat with chronic renal failure through inhibiting RhoA/ROCK signaling pathway

Endothelial cells injury and activation contribute to arteriovenous fistula (AVF) stenosis. Hirudin (Hiru) can inhibit the activity of thrombin, which was reported to enhance endothelial cell permeability and promote vascular inflammatory responses. RhoA/ROCK signaling pathway is also important in regulating vascular endothelial permeability. This study aimed to investigate the role of Hiru on the viability and permeability of human umbilical vein endothelial cells (HUVECs) following stimulation of serum from rat with chronic renal failure (CRF) and illustrated the effects of Hiru on RhoA/ROCK signaling. Wistar rats were randomly divided into control group and CRF group. Serum from each group was collected to stimulate HUVECs. Proliferation capability was estimated with Cell Count Kit-8 (CCK-8) assay. Transwell assay was performed to determine permeability. Cell apoptosis was examined using Tunel staining. Telomere length and telomerase activity were determined by qPCR. Moreover, the expression of RhoA, ROCK1 and ROCK2 was estimated via western blot. Results showed that the serum from CRF rat significantly inhibited cell viability while enhanced cell permeability and apoptosis. Different concentrations of Hiru prevented the above effects caused by CRF serum. Additionally, Hiru recovered the CRF serum-induced decreased telomere length and telomerase activity. Hiru also inhibited the protein expression of RhoA, ROCK1 and ROCK2, which were activated by CRF serum. Moreover, the ROCK inhibitor, Y27632, exhibited similar effects with Hiru. In conclusion, Hiru-restored HUVECs cell viability, telomere length and telomerase activity, suppressed permeability and apoptosis in the presence of CRF serum might depend on inactivating the RhoA/ROCK signaling.

Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.

Peer-reviewed research on anticoagulant and antithrombotic drug development relevant to leech-derived and synthetic compounds. Indexed in PubMed and verified against the NCBI record.

Leech-derived molecules this paper discusses, each with a full profile in the ASH compound registry:

Explore cómo esta investigación se conecta con la práctica clínica

More peer-reviewed studies in Desarrollo de fármacos.

• Novel Leech Antimicrobial Peptides — Hirunipins — Kumar et al. (2025)
• Medicinal Leech Genome Assembly — Anticoagulant Gene Catalog — Kvist et al. (2020)
• Effects of hirudotherapy on liver functions, lipid profile, and insulin sensitivity in rats with metabolic syndrome — Bilden A et al. (2026)
• HIRUDOTHERAPY IN PRESBYACUZIS PRAECOX IN CLEAN-UP WORKERS AFTER THE CHORNOBYL ACCIDENT DURING THE POST-CATASTROPHE YEARS — Zabolotnyi D, Mishchanchuk N (2019)
• [Hirudo medicinalis-leech applications in plastic and reconstructive microsurgery--a literature review] — Knobloch K et al. (2007)
• Recombinant hirudin in clinical practice: focus on lepirudin — Greinacher A, Lubenow N (2001)
• In-vitro antileishmanial potential of peptide drug hirudin — Khan H et al. (2017)
• Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines — Garcia DA, Baglin TP, Weitz JI, Samama MM (2012)
• Direct thrombin inhibitors — Lee CJ, Ansell JE (2011)
• Updates on Use and Monitoring of Direct Thrombin Inhibitors — Navaei A et al. (2026)

Browse all ASH-analysed research →