title: Involvement of proteasome and macrophages M2 in the protection afforded by telmisartan against the acute myocardial infarction in Zucker diabetic fatty rats with metabolic syndrome.
abstract: This study investigated the involvement of proteasome and macrophages M2 in the protection afforded by telmisartan against the acute myocardial infarction in Zucker diabetic fatty (ZDF) rats with metabolic syndrome. ZDF rats were treated for three weeks with telmisartan at doses of 7 and 12 mg/kg/day. After treatment, rats were subjected to a 25 min occlusion of the left descending coronary artery followed by 2 h reperfusion (I/R). At the end of the I/R period, biochemical, immunohistochemical, and echocardiographic evaluations were done. Telmisartan treatment (7 mg/kg and 12 mg/kg) reduced the myocardial infarct size, the expression of proteasome subunits 20S and 26S, and the protein ubiquitin within the heart. The compound has led to an increased M2 macrophage phenotype within the cardiac specimens and a modification of the cardiac cytokine and chemokine profile. This was functionally translated in improved cardiac performance as evidenced by echography after 2 h reperfusion. 7 mg/kg/day telmisartan was sufficient to improve the left ventricular ejection fraction LVEF of the rat heart recorded after I/R (e.g., vehicle 38 ± 2.2%; telmisartan 54 ± 2.7%) and was sufficient to improve the diastolic function and the myocardial performance index up to values of 0.6 ± 0.01 measured after I/R.
authors.affiliation: Department of Experimental Medicine, Section of Pharmacology "L. Donatelli", Second University of Naples, 80138 Naples, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Di Filippo
authors.affiliation: Radiology, Radiotherapy and Nuclear Medicine Unit, Second University of Naples, 80138 Naples, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Rossi
authors.affiliation: Department of Experimental Medicine, Section of Pharmacology "L. Donatelli", Second University of Naples, 80138 Naples, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Ferraro
authors.affiliation: Department of Experimental Medicine, Section of Pharmacology "L. Donatelli", Second University of Naples, 80138 Naples, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Maisto
authors.affiliation: Department of Experimental Medicine, Section of Pharmacology "L. Donatelli", Second University of Naples, 80138 Naples, Italy.
authors.forename: A
authors.initials: A
authors.lastname: De Angelis
authors.affiliation: Department of Clinical, Public and Preventive Medicine, Second University of Naples, 80138 Naples, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Ferraraccio
authors.affiliation: Radiology, Radiotherapy and Nuclear Medicine Unit, Second University of Naples, 80138 Naples, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Rotondo
authors.affiliation: Department of Experimental Medicine, Section of Pharmacology "L. Donatelli", Second University of Naples, 80138 Naples, Italy.
authors.forename: M
authors.initials: M
authors.lastname: D'Amico
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000627:therapeutic use*; D001565:Benzoates / Q000627:therapeutic use*; D008264:Macrophages / Q000378:metabolism*; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000276:immunology; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000276:immunology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D051381:Rats; D011924:Rats, Zucker; D000077333:Telmisartan
chemical_list: D001562:Benzimidazoles; D001565:Benzoates; D046988:Proteasome Endopeptidase Complex; D000077333:Telmisartan
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