PMID- 32968622 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220417 IS - 2223-3652 (Print) IS - 2223-3660 (Electronic) IS - 2223-3652 (Linking) VI - 10 IP - 4 DP - 2020 Aug TI - Inhibition of ERK or Akt ameliorates intimal hyperplasia via up-regulation of Cx37 and down-regulation of Cx43 in balloon injury rat model. PG - 658-666 LID - 10.21037/cdt-20-345 [doi] AB - BACKGROUND: Connexins (Cxs) are reported to participate in atherosclerosis associated intimal hyperplasia (IH), while their function involved in the balloon injury (BI) induced IH and restenosis is less reported. METHODS: Forty-eight male Sprague-Dawley rats were randomly assigned to not injured (NI) group and BI group, which were further administrated with ERK-inhibitor U0216 and Akt-inhibitor MIK2206. Western blot and RT-PCR were utilized to detect the expression of Cx30, Cx37, Cx40, and Cx43 at 6 hours, 24 hours, 7 days, and 14 days post-surgery. H&E staining and related intima area, media area, and luminal area measurement were applied to indicate neointima formation and IH. ERK and Akt phosphorylation levels and proliferating cell nuclear antigen (PCNA) immunostaining were also detected. RESULTS: Among the four Cxs detected, Cx37 showed down-regulated, and Cx43 showed up-regulated temporal expression pattern in BI rats with confirmed neointima formation. Up-regulated p-ERK (P<0.01) and p-Akt (P<0.01) can be detected in BI rats compared with NI rats. Meanwhile, U0216 and MIK2206 can significantly reduce Cx43 expression and increase CX37 expression accompanied with reduced neointima formation and PCNA staining (P<0.05 or P<0.01) in BI rats. CONCLUSIONS: ERK or Akt inhibition can alleviate BI-induced IH via up-regulation of Cx37 and down-regulation of Cx43. CI - 2020 Cardiovascular Diagnosis and Therapy. All rights reserved. FAU - Pan, Lemen AU - Pan L AD - Department of Vascular Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. FAU - Ni, Haizhen AU - Ni H AD - Department of Vascular Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. FAU - Jin, Wenxu AU - Jin W AD - Department of Vascular Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. FAU - Su, Xiang AU - Su X AD - Department of Vascular Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. LA - eng PT - Journal Article PL - China TA - Cardiovasc Diagn Ther JT - Cardiovascular diagnosis and therapy JID - 101601613 PMC - PMC7487390 OTO - NOTNLM OT - Akt OT - Cx37 OT - Cx43 OT - ERK OT - intimal hyperplasia (IH) COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/cdt-20-345). The authors have no conflicts of interest to declare. EDAT- 2020/09/25 06:00 MHDA- 2020/09/25 06:01 PMCR- 2020/08/01 CRDT- 2020/09/24 05:34 PHST- 2020/09/24 05:34 [entrez] PHST- 2020/09/25 06:00 [pubmed] PHST- 2020/09/25 06:01 [medline] PHST- 2020/08/01 00:00 [pmc-release] AID - cdt-10-04-658 [pii] AID - 10.21037/cdt-20-345 [doi] PST - ppublish SO - Cardiovasc Diagn Ther. 2020 Aug;10(4):658-666. doi: 10.21037/cdt-20-345.