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.

• Publication year

  2020

• Venue

  Drug development research (Print)

• Publication date

  2020-12-20

• Fields of study

  Medicine

• Identifiers
  DOI 10.1002/ddr.21773PMID 33345328
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Hirudin reduces nephropathy microangiopathy in STZ-induced diabetes rats by inhibiting endothelial cell migration and angiogenesis.

  2020cited by this paper
• Executive summary for the 2015 Annual Data Report of the China Kidney Disease Network (CK-NET).

  2019influential reference
• The effects of a hirudin/liposome complex on a diabetic nephropathy rat model

  2019cited by this paper
• Role of a RhoA/ROCK-Dependent Pathway on Renal Connexin43 Regulation in the Angiotensin II-Induced Renal Damage

  2019cited by this paper
• Determinants of Arteriovenous Fistula Maturation.

  2018cited by this paper
• Hirudin Protects Ang II-Induced Myocardial Fibroblasts Fibrosis by Inhibiting the Extracellular Signal-Regulated Kinase1/2 (ERK1/2) Pathway

  2018cited by this paper
• Balance between senescence and apoptosis is regulated by telomere damage–induced association between p16 and caspase-3

  2018influential reference
• RhoA/ROCK-2 Pathway Inhibition and Tight Junction Protein Upregulation by Catalpol Suppresses Lipopolysaccaride-Induced Disruption of Blood-Brain Barrier Permeability

  2018cited by this paper
• Role of thrombin in the pathogenesis of atherosclerosis

  2018influential reference
• Arteriovenous Fistula Maturation in Prevalent Hemodialysis Patients in the United States: A National Study.

  2018cited by this paper
• The Role of RhoA in Neovascular-Related Functions of Endothelial Progenitor Cells Induced by AngiotensinⅡ

  2018cited by this paper
• Hirudin variants production by genetic engineered microbial factory

  2018cited by this paper
• Intimal Hyperplasia, Stenosis, and Arteriovenous Fistula Maturation Failure in the Hemodialysis Fistula Maturation Study.

  2017cited by this paper
• Low dose of alcohol attenuates pro-atherosclerotic activity of thrombin.

  2017cited by this paper
• Raf-1/CK2 and RhoA/ROCK signaling promote TNF-α-mediated endothelial apoptosis via regulating vimentin cytoskeleton.

  2017cited by this paper
• Dasatinib inhibits actin fiber reorganization and promotes endothelial cell permeability through RhoA‐ROCK pathway

  2017cited by this paper
• New Insights into Dialysis Vascular Access: Molecular Targets in Arteriovenous Fistula and Arteriovenous Graft Failure and Their Potential to Improve Vascular Access Outcomes.

  2016cited by this paper
• Effect of regional versus local anaesthesia on outcome after arteriovenous fistula creation: a randomised controlled trial.

  2016cited by this paper
• Rutin Prevents High Glucose-Induced Renal Glomerular Endothelial Hyperpermeability by Inhibiting the ROS/Rhoa/ROCK Signaling Pathway

  2016cited by this paper
• Activation of RhoA-ROCK-BMP signaling reprograms adult human corneal endothelial cells

  2014cited by this paper
• Telomere and telomerase biology.

  2014cited by this paper
• Diabetes Causes Bone Marrow Endothelial Barrier Dysfunction by Activation of the RhoA–Rho-Associated Kinase Signaling Pathway

  2013cited by this paper
• Adventitial transduction of lentivirus-shRNA-VEGF-A in arteriovenous fistula reduces venous stenosis formation

  2013cited by this paper
• Arteriovenous access failure: more than just intimal hyperplasia?

  2013cited by this paper
• Atherosclerotic intracranial arterial stenosis: risk factors, diagnosis, and treatment.

  2013cited by this paper
• Chronic kidney disease accelerates endothelial barrier dysfunction in a mouse model of an arteriovenous fistula.

  2013cited by this paper
• Preoperative venous intimal hyperplasia, postoperative arteriovenous fistula stenosis, and clinical fistula outcomes.

  2013cited by this paper
• Two distinct dysfunctions in diabetic mouse mesenteric artery contraction are caused by changes in the Rho A-Rho kinase signaling pathway.

  2012cited by this paper
• Vascular smooth muscle cell proliferation in restenosis.

  2011cited by this paper
• Effect of clopidogrel on early failure of arteriovenous fistulas for hemodialysis: a randomized controlled trial.

  2008cited by this paper
• Regulation of vascular smooth muscle cell differentiation.

  2007cited by this paper
• Hirudin In Renal Insufficiency

  2002cited by this paper
• Recombinant Hirudin in Clinical Practice

  2001cited by this paper
• Recombinant Hirudin in Clinical Practice: Focus on Lepirudin

  2001cited by this paper
• Haemodialysis.

  1999cited by this paper
• Flow-induced arterial enlargement is inhibited by suppression of nitric oxide synthase activity in vivo.

  1997cited by this paper
• Haemodialysis

  1959cited by this paper

• TET1-Mediated DNA hydroxymethylation of KLF6 promotes LPS-induced pulmonary fibrosis by activating the S1PR3/RhoA/ROCK signaling pathway

  2025cites this paper
• Impact of Bivalirudin on Ischemia/Reperfusion Injury in Patients with Reperfused STEMI Assessed by Cardiac Magnetic Resonance

  2024cites this paper
• Unveiling the role of RhoA and ferroptosis in vascular permeability: Implications for osteoarthritis

  2024cites this paper
• Hirudin in the Treatment of Chronic Kidney Disease

  2024cites this paper
• Integrated analysis of mRNA and microRNA expression profiles in hepatopancreas of Litopenaeus vannamei under acute exposure to MC-LR

  2023cites this paper
• ROCK inhibitor: Focus on recent updates

  2023cites this paper
• Melatonin inhibits the formation of intraplaque neovessels in ApoE-/- mice via PPARγ- RhoA-ROCK pathway.

  2023cites this paper
• Baseline Ratio of Soluble Fas/FasL Predicts Onset of Pulmonary Hypertension in Elder Patients Undergoing Maintenance Hemodialysis: A Prospective Cohort Study

  2022cites this paper
• Network Pharmacology and In Vitro Experimental Verification Reveal the Mechanism of the Hirudin in Suppressing Myocardial Hypertrophy

  2022cites this paper
• Quercetin regulates vascular endothelium function in chronic renal failure via modulation of Eph/Cav‐1 signaling

  2022cites this paper
• High Glucose Aggravates Retinal Endothelial Cell Dysfunction by Activating the RhoA/ROCK1/pMLC/Connexin43 Signaling Pathway

  2022cites this paper
• Bivalirudin Attenuates Thrombin-Induced Endothelial Hyperpermeability via S1P/S1PR2 Category: Original Articles

  2021cites this paper
• Hydroxysafflor Yellow A inhibits the viability and migration of vascular smooth muscle cells induced by serum from rats with chronic renal failure via inactivation of the PI3K/Akt signaling pathway

  2021cites this paper