Distinct acute myocardial gene expression profiles after pressure and volume overload.

• Type: Summary of Presentation in an International Conference
• Date: 2005

Authors

Roncon-Albuquerque R Jr (Author) FMUP; Vasconcelos M (Author) Other; Lourenço AP (Author) FMUP; Brandão-Nogueira A (Author) Other; Teles A (Author) FMUP; Leite-Moreira AF (Author) FMUP

Conference proceedings International

Title: European Journal of Heart Failure

Initial page: 134

ESC Annual Congress 2005

Stockholm, Sweden , 03 a 07 de Setembro de 2005

Scientific classification

FOS: Medical and Health sciences > Other medical sciences

Other information

Resumo (PT): Despite the extensive knowledge on myocardial hypertrophy, molecular remodeling and disturbed gene expression in chronic overload, the patterns of genetic response to acute cardiac overload remain largely unknown. This study evaluates biventricular gene expression after acute volume and RV pressure overload in vivo. Male Wistar rats were assigned to pulmonary trunk banding (P-Band; n=13), dextran40 infusion at 5mL/h (Dxt; n=13) or sham procedures (n=13) and hemodynamicaly monitored with pressure micromanometers. RV and LV free-wall samples were collected at 120min (n=22) and 360min (n=18) for mRNA quantification (RT-realtime PCR) of BNP, TNF-alfa, IL-6, IGF-1, SERCA2a, phospholamban (PLB) and calsequestrin (CSQ) normalized for GAPDH. Results are expressed as arbitrary units (AU) using sham group as reference (1AU). In Dxt, end-diastolic pressure progressively increased in both ventricles, while systolic pressure was only progressively increased in the RV. Distinctly, P-Band induced an immediate and sustained increase of RV systolic pressure accompained by a late increase (at 240rain) of RV enddiastolic pressure, but did not alter LV hemodynamics. CSQ mRNA increased in the LV of P-Band and Dxt, which precluded its use as a normalizer gene. Ca 2+ regulating proteins mRNA was only significantly increased 360rain after volume overload: SERCA2a increased in both RV and LV (7.6-t-2.7 and 3.9-t-0.8, respectively), while PLB was only increased in the RV (2.94-0.5). BNP upregulation was observed in the overloaded RV of P-Band (3.0-t-0.7) and RV and LV of Dxt (2.8-t-0.9, and 2.24-0.5, respectively), while IGF-1 increased in the RV of both PBand and Dxt protocols at 360rain (2.2-t-0.1 and 2.1-t-0.2, respectively). Inflammatory mediator genes were also accutely modulated. IL-6 mRNA was markedly increased in the RV and LV of 360rain volume overloaded hearts (9.14-2.7 and 11.64-3.1, respectively) and transiently raised at 120rain in the RV of P-Band (3.84-1.2), whereas TNF-alfa was increased in the two ventricles of both protocols: RV Dxt (3.64-1.6 and 51.54-10.9, at 120 and 360rain, respectively), RV P-Band (7.3-t-2.3, at 360rain), LV of P-Band and Dxt at 360rain (11.0-t-3.2 and 12.5-t-1.6, respectively). Acute shifts in gene expression profiles following cardiac overload are distinct in pressure and volume overload and include regression to the molecular fetal phenotype, local activation of cytokines and growth factors, and disturbed expression of genes involved in Ca 2+ kinetics. These might contribute to the distinct patterns of ventricular remodeling observed later on in the progression to heart failure.

Language: English

Type (Professor's evaluation): Scientific

Notes: ESC Annual Congress 2005, published in journal, European Journal of Heart Failure, 2005;4(Suppl.1):134.