title: Myocardial gene expression of microRNA-133a and myosin heavy and light chains, in conjunction with clinical parameters, predict regression of left ventricular hypertrophy after valve replacement in patients with aortic stenosis.
abstract: BACKGROUND
  Left ventricular (LV) reverse remodelling after valve replacement in aortic stenosis (AS) has been classically linked to the hydraulic performance of the replacement device, but myocardial status at the time of surgery has received little attention.
  
  
  OBJECTIVE
  To establish predictors of LV mass (LVM) regression 1 year after valve replacement in a surgical cohort of patients with AS based on preoperative clinical and echocardiographic parameters and the myocardial gene expression profile at surgery.
  
  
  METHODS
  Transcript levels of remodelling-related proteins and regulators were determined in LV intraoperative biopsies from 46 patients with AS by RT-PCR. Using multiple linear regression analysis, an equation was developed (adjusted R²=0.73; p<0.0001) that included positive [preoperative LVM, microRNA-133a, serum response factor (SRF, which is known to be a transactivator of miR-133) and age] and negative [body mass index (BMI), Wolf-Hirschhorn syndrome candidate-2 (WHSC2, which is a target for repression by miR-133a), β-myosin heavy chain, myosin light chain-2, diabetes mellitus, and male gender] independent predictors of LVM reduction.
  
  
  RESULTS
  Aortic valve area gain or the reduction in transvalvular gradient maintained no significant relationships with the dependent variable. Logistic regression analysis identified microRNA-133a as a significant positive predictor of LVM normalisation, whereas β-myosin heavy chain and BMI constituted negative predictors.
  
  
  CONCLUSIONS
  Hypertrophy regression 1 year after pressure overload release is related to the preoperative myocardial expression of remodelling-related genes, in conjunction with the patient's clinical background. In this scenario, miR-133 emerges as a key element of the reverse remodelling process. Postoperative improvement of valve haemodynamics does not predict the degree of hypertrophy regression or LVM normalisation. These results led us to reconsider the current reverse remodelling paradigm and (1) to include criteria of hypertrophy reversibility in the decision algorithm used to decide timing for the operation; and (2) to modify other prevailing factors (overweight, diabetes, etc) known to maintain LV hypertrophy.
authors.affiliation: Department of Physiology and Pharmacology, University of Cantabria School of Medicine, Spain.
authors.forename: Ana V
authors.initials: AV
authors.lastname: Villar
authors.forename: David
authors.initials: D
authors.lastname: Merino
authors.forename: Mareike
authors.initials: M
authors.lastname: Wenner
authors.forename: Miguel
authors.initials: M
authors.lastname: Llano
authors.forename: Manuel
authors.initials: M
authors.lastname: Cobo
authors.forename: Cecilia
authors.initials: C
authors.lastname: Montalvo
authors.forename: Raquel
authors.initials: R
authors.lastname: García
authors.forename: Rafael
authors.initials: R
authors.lastname: Martín-Durán
authors.forename: Juan M
authors.initials: JM
authors.lastname: Hurlé
authors.forename: María A
authors.initials: MA
authors.lastname: Hurlé
authors.forename: J Francisco
authors.initials: JF
authors.lastname: Nistal
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001024:Aortic Valve Stenosis / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics / Q000601:surgery*; D001706:Biopsy; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005838:Genotype; D019918:Heart Valve Prosthesis Implantation; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000235:genetics*; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D035683:MicroRNAs / Q000032:analysis*; D008875:Middle Aged; D009206:Myocardium / Q000737:chemistry*; D018995:Myosin Heavy Chains / Q000235:genetics*; D018994:Myosin Light Chains / Q000235:genetics*; D010641:Phenotype; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D012307:Risk Factors; D013030:Spain; D013997:Time Factors; D016896:Treatment Outcome; D014463:Ultrasonography; D020257:Ventricular Remodeling / Q000235:genetics*
chemical_list: C548234:MIRN133 microRNA, human; D035683:MicroRNAs; D018994:Myosin Light Chains; D018995:Myosin Heavy Chains