title: Effects of renin-angiotensin system inhibitors on fibrosis in patients with alcoholic chronic pancreatitis.
abstract: Chronic pancreatitis (CP) results in impairment of exocrine as well as endocrine functions and progressive fibrosis. Previous studies, have demonstrated the presence of renin-angiotensin system receptors within different pancreatic cells. The aim of the present study was to assess the effects of renin-angiotensin system (RAS) inhibitors on serum levels of fibrosis biomarkers (matrix metalloproteinase 2 and 9 (MMP-2, MMP-9), tissue inhibitor of MMP (TIMP- 1, TIMP-2), hyaluronic acid (HA)) and fasting glucose levels in patients with alcoholic CP. Seventy seven outpatients (mean age 43 years, 62 males) with diagnosed alcoholic CP were randomly enrolled into 5 study groups depending on the RAS inhibitors administered and their doses (2.5 or 5 mg and 12.5 or 25 mg for ramipril or losartan, respectively). Venous blood was sampled monthly for a period of one year to monitor serum drug levels. MMP-2, -9, TIMP-1, TIMP-2 and HA were measured with ELISA method on the onset and at the end of the study. Only forty five patients regularly participated in follow-up visits and completed the study. The fluctuations in serum HA levels observed among patients from the remaining groups also did not reach statistical significance. Serum MMP-2 levels (P = 0.06) and MMP-2/TIMP-1 ratio (P = 0.06) showed increasing tendency in the losartan 25 mg group. High doses of ramipril and losartan statistically significantly reduced fasting glucose levels. High doses of losartan can increase the MMP-2 activity in serum of alcoholic CP patients, which potentially is likely to affect turnover of extracellular matrix proteins within the pancreas. Moreover, high doses of both RAS inhibitors decrease the fasting glucose level.
authors.affiliation: Department of Gastroenterology with Endoscopic Unit, Medical University of Lublin, Lublin, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Madro
authors.affiliation: Department of Medical Chemistry, Medical University of Lublin, Lublin, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Kurzepa
authors.affiliation: Department of Gastroenterology with Endoscopic Unit, Medical University of Lublin, Lublin, Poland. celinski.krzysztof@gmail.com.
authors.forename: K
authors.initials: K
authors.lastname: Celinski
authors.affiliation: Department of Gastroenterology with Endoscopic Unit, Medical University of Lublin, Lublin, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Slomka
authors.affiliation: Department of Gastroenterology with Endoscopic Unit, Medical University of Lublin, Lublin, Poland.
authors.forename: G
authors.initials: G
authors.lastname: Czechowska
authors.affiliation: Department of Radiology and Nuclear Medicine, University Hospital No 4 of Lublin, Lublin, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Kurzepa
authors.affiliation: Department of Gastroenterology with Endoscopic Unit, Medical University of Lublin, Lublin, Poland.
authors.forename: W
authors.initials: W
authors.lastname: Kazmierak
authors.affiliation: Department of Forensic Medicine, Medical University of Lublin, Lublin, Poland.
authors.forename: G
authors.initials: G
authors.lastname: Buszewicz
authors.affiliation: Department of Forensic Medicine, Medical University of Lublin, Lublin, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Ciesielka
authors.affiliation: Department of Forensic Medicine, Medical University of Lublin, Lublin, Poland.
authors.forename: R
authors.initials: R
authors.lastname: Madro
mesh_terms: D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000188:drug therapy* / Q000209:etiology*; D019808:Losartan / Q000627:therapeutic use; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D050500:Pancreatitis, Chronic / Q000097:blood / Q000150:complications*; D017257:Ramipril / Q000627:therapeutic use; D012084:Renin-Angiotensin System / Q000187:drug effects*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D019808:Losartan; D017257:Ramipril