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Upregulation of angiotensin-converting enzyme (ACE) 2 in hepatic fibrosis by ACE inhibitors.
Clin Exp Pharmacol Physiol. 2010 Jan; 37(1):e1-6.CE

Abstract

1. The role of angiotensin-converting enzyme (ACE) 2 is likely to balance the status of the renin-angiotensin system (RAS) by degrading angiotensin (Ang) II and generating Ang-(1-7). Earlier demonstrations that ACE2 is insensitive to ACE inhibitors prompted us to evaluate the effect of ACE inhibitors on ACE2 expression. 2. Liver fibrosis was induced in rats with 40% CCl(4) (2.5 mL/kg, s.c., twice per week). Half the rats were further treated with perindopril (2 mg/kg, p.o., daily). After 2 and 4 weeks treatment, ACE2 immunoreactivity was assessed by immunohistochemical staining, ACE2 protein expression was determined by western blot and mRNA expression of ACE2 and the Ang-(1-7) receptor Mas was determined by reverse transcription-polymerase chain reaction (RT-PCR). 3. As an in vitro study, hepatic stellate cells (HSC) were treated with AngII (0.1-10 micromol/L) alone or in combination with the synthesized peptide ACEI (Sigma-Aldrich). Western blot and RT-PCR were used to evaluate ACE2 expression and Mas mRNA levels. Furthermore, after treatment of HSC with the Mas antagonist A779 (1 micromol/L), the protein expression of connective tissue growth factor (CTGF) was detected to evaluate the interaction between AngII, ACEI and the ACE2-Mas axis. 4. Expression of both ACE2 mRNA and protein and Mas mRNA was markedly upregulated in both CCl(4)-injured rat liver and AngII-treated HSC. Further significant upregulation was observed following additional administration of ACEI. In addition, ACEI treatment of HSC inhibited AngII-induced overexpression of connective tissue growth factor and this effect was ameliorated by blockade of the Mas receptor with A779. 5. The findings of the present study suggest that ACE inhibitors are able to upregulate ACE2 under conditions of liver injury both in vivo and in vitro, which may indicate potential benefits of ACE inhibitors in the therapeutic treatment of liver fibrosis.

Authors+Show Affiliations

Institute for Digestive Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19793108

Citation

Huang, Mao-liang, et al. "Upregulation of Angiotensin-converting Enzyme (ACE) 2 in Hepatic Fibrosis By ACE Inhibitors." Clinical and Experimental Pharmacology & Physiology, vol. 37, no. 1, 2010, pp. e1-6.
Huang ML, Li X, Meng Y, et al. Upregulation of angiotensin-converting enzyme (ACE) 2 in hepatic fibrosis by ACE inhibitors. Clin Exp Pharmacol Physiol. 2010;37(1):e1-6.
Huang, M. L., Li, X., Meng, Y., Xiao, B., Ma, Q., Ying, S. S., Wu, P. S., & Zhang, Z. S. (2010). Upregulation of angiotensin-converting enzyme (ACE) 2 in hepatic fibrosis by ACE inhibitors. Clinical and Experimental Pharmacology & Physiology, 37(1), e1-6. https://doi.org/10.1111/j.1440-1681.2009.05302.x
Huang ML, et al. Upregulation of Angiotensin-converting Enzyme (ACE) 2 in Hepatic Fibrosis By ACE Inhibitors. Clin Exp Pharmacol Physiol. 2010;37(1):e1-6. PubMed PMID: 19793108.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Upregulation of angiotensin-converting enzyme (ACE) 2 in hepatic fibrosis by ACE inhibitors. AU - Huang,Mao-liang, AU - Li,Xu, AU - Meng,Ying, AU - Xiao,Bing, AU - Ma,Qiang, AU - Ying,Song-song, AU - Wu,Ping-sheng, AU - Zhang,Zhen-shu, Y1 - 2009/09/28/ PY - 2009/10/2/entrez PY - 2009/10/2/pubmed PY - 2010/6/11/medline SP - e1 EP - 6 JF - Clinical and experimental pharmacology & physiology JO - Clin Exp Pharmacol Physiol VL - 37 IS - 1 N2 - 1. The role of angiotensin-converting enzyme (ACE) 2 is likely to balance the status of the renin-angiotensin system (RAS) by degrading angiotensin (Ang) II and generating Ang-(1-7). Earlier demonstrations that ACE2 is insensitive to ACE inhibitors prompted us to evaluate the effect of ACE inhibitors on ACE2 expression. 2. Liver fibrosis was induced in rats with 40% CCl(4) (2.5 mL/kg, s.c., twice per week). Half the rats were further treated with perindopril (2 mg/kg, p.o., daily). After 2 and 4 weeks treatment, ACE2 immunoreactivity was assessed by immunohistochemical staining, ACE2 protein expression was determined by western blot and mRNA expression of ACE2 and the Ang-(1-7) receptor Mas was determined by reverse transcription-polymerase chain reaction (RT-PCR). 3. As an in vitro study, hepatic stellate cells (HSC) were treated with AngII (0.1-10 micromol/L) alone or in combination with the synthesized peptide ACEI (Sigma-Aldrich). Western blot and RT-PCR were used to evaluate ACE2 expression and Mas mRNA levels. Furthermore, after treatment of HSC with the Mas antagonist A779 (1 micromol/L), the protein expression of connective tissue growth factor (CTGF) was detected to evaluate the interaction between AngII, ACEI and the ACE2-Mas axis. 4. Expression of both ACE2 mRNA and protein and Mas mRNA was markedly upregulated in both CCl(4)-injured rat liver and AngII-treated HSC. Further significant upregulation was observed following additional administration of ACEI. In addition, ACEI treatment of HSC inhibited AngII-induced overexpression of connective tissue growth factor and this effect was ameliorated by blockade of the Mas receptor with A779. 5. The findings of the present study suggest that ACE inhibitors are able to upregulate ACE2 under conditions of liver injury both in vivo and in vitro, which may indicate potential benefits of ACE inhibitors in the therapeutic treatment of liver fibrosis. SN - 1440-1681 UR - https://www.unboundmedicine.com/medline/citation/19793108/Upregulation_of_angiotensin_converting_enzyme__ACE__2_in_hepatic_fibrosis_by_ACE_inhibitors_ L2 - https://doi.org/10.1111/j.1440-1681.2009.05302.x DB - PRIME DP - Unbound Medicine ER -