title: The effect of fluvastatin on cardiac fibrosis and angiotensin-converting enzyme-2 expression in glucose-controlled diabetic rat hearts.
abstract: Independently of the lipid-lowering effects, statin has been reported to attenuate the development of diabetic cardiomyopathy. However, the effect of statin in glucose-controlled diabetic condition has not been demonstrated. We evaluated the effect of fluvastatin on cardiac function, fibrosis, and angiotensin-converting enzyme-2 (ACE2) expression in glucose-controlled diabetic rats. Male Wistar rats were randomly divided into four groups: control (Group C), diabetes (Group D), diabetes with insulin (Group I), and diabetes with insulin and fluvastatin (Group I+F). Diabetes was induced by a single injection of streptozotocin (65 mg/kg). After 8 weeks, the hearts were extracted following echocardiographic evaluation. Cardiac fibrosis was analyzed using Masson's trichrome stain. Collagens I and III and ACE2 expressions were evaluated by immunohistochemistry and western blot. Group D showed reduced cardiac systolic function compared to the other groups (all P < 0.05). However, diastolic function estimated by E/A ratio was significantly decreased in groups D and I (median: 0.88 and 1.45, respectively) compared to groups C and I+F (2.97 and 2.15) (all P < 0.05). Cardiac fibrosis was more severe in groups D and I than in groups C and I+F (all P < 0.05) on Masson's trichrome stain. On immunohistochemistry, ACE2 expression was significantly decreased only in group D (all P < 0.05). However, collagen I and III showed higher expressions in group D compared to groups C and I+F while no significant difference was observed compared with group I (all P < 0.05). On western blot, collagen I and ACE2 expressions in group D (median: 1.78 and 0.35, respectively) were significantly different from groups C (references: 1) and I+F (0.76 and 1.21) (all P < 0.05), but not from group I (1.19 and 0.92). Our study suggested a combination of fluvastatin and insulin would be more effective than insulin alone in diabetic hearts. However, the exact mechanism remains to be elucidated.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 06351, Korea.
authors.forename: Young Hee
authors.initials: YH
authors.lastname: Shin
authors.affiliation: Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 06351, Korea.
authors.forename: Jeong Jin
authors.initials: JJ
authors.lastname: Min
authors.affiliation: Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 06351, Korea. jonghwanlee75@gmail.com.
authors.forename: Jong-Hwan
authors.identifier: http://orcid.org/0000-0001-8249-5550
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 06351, Korea.
authors.forename: Eun-Hee
authors.initials: EH
authors.lastname: Kim
authors.affiliation: Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 06351, Korea.
authors.forename: Go Eun
authors.initials: GE
authors.lastname: Kim
authors.affiliation: Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 06351, Korea.
authors.forename: Myung Hee
authors.initials: MH
authors.lastname: Kim
authors.affiliation: Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 06351, Korea.
authors.forename: Jeong Jin
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 06351, Korea.
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Ahn
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental; D058065:Diabetic Cardiomyopathies / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D004452:Echocardiography; D000072396:Endothelin-Converting Enzymes / Q000096:biosynthesis*; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D005355:Fibrosis; D000077340:Fluvastatin; D005947:Glucose / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D000077340:Fluvastatin; C000606924:ECE2 protein, human; D000072396:Endothelin-Converting Enzymes; D005947:Glucose
keywords: Angiotensin-converting enzyme-2; Diabetic cardiomyopathy; Fluvastatin; Insulin