title: Interventional effect of valsartan on expression of inducible cAMP early repressor and phosphodiesterase 3A in rats after myocardial infarction.
abstract: To investigate the changes of inducible cAMP early repressor (ICER) and phosphodiesterase 3A in rats after myocardial infarction and to evaluate the beneficial effects of valsartan on cardiac function and ventricular remodeling. Rats were split into four groups: sham-operation group, pre-myocardial infarction group (valsartan administration 2 weeks before myocardial infarction), post-myocardial infarction group (valsartan administration after myocardial infarction) and myocardial infarction group (vehicle after myocardial infarction). Echocardiograph and hemodynamic data were measured and cardiocyte apoptosis was estimated by TUNEL staining. ICER, cAMP response element binding protein (CREB), phosphodiesterase 3A and Bcl-2 mRNA expression levels were assayed by real-time reverse transcriptase polymerase chain reaction and protein expression was measured using immunoblot analysis. ICER and CREB mRNA expression in the myocardial infarction group were higher and phosphodiesterase 3A and Bcl-2 mRNA expression were lower than the sham-operation group (Ps<0.01). Following the improvement of cardiac function and ventricular remodeling, ICER and CREB mRNA in pre- and post- myocardial-infarction groups were down-regulated, and phosphodiesterase 3A and Bcl-2 mRNA were up-regulated (P<0.05). The changes brought on by valsartan pre-myocardial infarction were stronger than post-myocardial infarction (P<0.05). These data suggest that there is a phosphodiesterase 3A-ICER positive-feedback loop leading to myocyte apoptosis and ongoing development of heart failure after myocardial infarction. Maintaining the function of phosphodiesterase 3A or reducing ICER may be an effective way to prevent myocardium apoptosis and heart dysfunction. Valsartan can ameliorate ventricular remodeling and heart failure by inhibiting the expression of ICER and increasing the expression of phosphodiesterase 3A.
authors.affiliation: Cardiovascular Department, First Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Ma
authors.forename: Lu
authors.initials: L
authors.lastname: Fu
authors.forename: Jingxia
authors.initials: J
authors.lastname: Shen
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
authors.forename: Yufei
authors.initials: Y
authors.lastname: Gao
authors.forename: Rongsheng
authors.initials: R
authors.lastname: Xie
authors.forename: Yuanshi
authors.initials: Y
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Han
authors.forename: Yumei
authors.initials: Y
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D006332:Cardiomegaly / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051786:Cyclic AMP Response Element Modulator / Q000235:genetics*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3 / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006333:Heart Failure / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009203:Myocardial Infarction / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051381:Rats; D013777:Tetrazoles / Q000494:pharmacology*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D057911:Angiotensin Receptor Antagonists; C497412:Crem protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; D013777:Tetrazoles; D051786:Cyclic AMP Response Element Modulator; D000068756:Valsartan; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D014633:Valine