title: Involvement of L-type calcium channel and SERCA2a in myocardial dysfunction induced by obesity.
abstract: Obesity has been shown to impair myocardial performance. Nevertheless, the mechanisms underlying the participation of calcium (Ca(2+) ) handling on cardiac dysfunction in obesity models remain unknown. L-type Ca(2+) channels and sarcoplasmic reticulum (SR) Ca(2+) -ATPase (SERCA2a), may contribute to the cardiac dysfunction induced by obesity. The purpose of this study was to investigate whether myocardial dysfunction in obese rats is related to decreased activity and/or expression of L-type Ca(2+) channels and SERCA2a. Male 30-day-old Wistar rats were fed standard (C) and alternately four palatable high-fat diets (Ob) for 15 weeks. Obesity was determined by adiposity index and comorbidities were evaluated. Myocardial function was evaluated in isolated left ventricle papillary muscles under basal conditions and after inotropic and lusitropic maneuvers. L-type Ca(2+) channels and SERCA2a activity were determined using specific blockers, while changes in the amount of channels were evaluated by Western blot analysis. Phospholamban (PLB) protein expression and the SERCA2a/PLB ratio were also determined. Compared with C rats, the Ob rats had increased body fat, adiposity index and several comorbidities. The Ob muscles developed similar baseline data, but myocardial responsiveness to post-rest contraction stimulus and increased extracellular Ca(2+) was compromised. The diltiazem promoted higher inhibition on developed tension in obese rats. In addition, there were no changes in the L-type Ca(2+) channel protein content and SERCA2a behavior (activity and expression). In conclusion, the myocardial dysfunction caused by obesity is related to L-type Ca(2+) channel activity impairment without significant changes in SERCA2a expression and function as well as L-type Ca(2+) protein levels.
authors.affiliation: Department of Clinical and Cardiology, School of Medicine, UNESP- State University Júlio Mesquita Filho, Botucatu, São Paulo, Brazil. andresoaresleopoldo@gmail.com
authors.forename: André Soares
authors.initials: AS
authors.lastname: Leopoldo
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Lima-Leopoldo
authors.forename: Mário Mateus
authors.initials: MM
authors.lastname: Sugizaki
authors.forename: André Ferreira
authors.initials: AF
authors.lastname: do Nascimento
authors.forename: Dijon Henrique Salomé
authors.initials: DH
authors.lastname: de Campos
authors.forename: Renata de Azevedo Melo
authors.initials: Rde A
authors.lastname: Luvizotto
authors.forename: Edson
authors.initials: E
authors.lastname: Castardeli
authors.forename: Carlos Augusto Barnabé
authors.initials: CA
authors.lastname: Alves
authors.forename: Patrícia Chakur
authors.initials: PC
authors.lastname: Brum
authors.forename: Antonio Carlos
authors.initials: AC
authors.lastname: Cicogna
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000096:biosynthesis / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D009202:Cardiomyopathies / Q000209:etiology / Q000503:physiopathology*; D004041:Dietary Fats / Q000008:administration & dosage; D004110:Diltiazem / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009765:Obesity / Q000150:complications* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000502:physiology*; D000099211:Phospholamban
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D002135:Calcium-Binding Proteins; D004041:Dietary Fats; D004110:Diltiazem; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban