Microarray analysis reveals pivotal divergent mRNA expression profiles early in the development of either compensated ventricular hypertrophy or heart failure.

@article{Buermans2005MicroarrayAR,
  title={Microarray analysis reveals pivotal divergent mRNA expression profiles early in the development of either compensated ventricular hypertrophy or heart failure.},
  author={Henk P. J. Buermans and Everaldo M Redout and Anja Schiel and Ren{\'e} J. P. Musters and Marian J. Zuidwijk and Paul P. Eijk and Cornelis van Hardeveld and Soemini Kasanmoentalib and Frans C. Visser and Bauke Ylstra and Warner S. Simonides},
  journal={Physiological genomics},
  year={2005},
  volume={21 3},
  pages={
          314-23
        }
}
Myocardial right ventricular (RV) hypertrophy due to pulmonary hypertension is aimed at normalizing ventricular wall stress. Depending on the degree of pressure overload, RV hypertrophy may progress to a state of impaired contractile function and heart failure, but this cannot be discerned during the early stages of ventricular remodeling. We tested whether critical differences in gene expression profiles exist between ventricles before the ultimate development of either a compensated or… 

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References

SHOWING 1-10 OF 55 REFERENCES

Induction of thyroid hormone-degrading deiodinase in cardiac hypertrophy and failure.

The induction of a cardiac TR-degrading deiodinase maybe expected to result in reduced cellular levels of T3 and thereby contribute to a local hypothyroid state in the hypertrophic and, particularly, in the failing ventricle.

Mechanical Load-Dependent Regulation of Gene Expression in Monocrotaline-Induced Right Ventricular Hypertrophy in the Rat

Enhanced biomechanical load is necessary to induce the gene expression changes associated with the hypertrophic phenotype of the pressure-overloaded RV.

Increased cardiomyocyte apoptosis and changes in proapoptotic and antiapoptotic genes bax and bcl-2 during left ventricular adaptations to chronic pressure overload in the rat.

In response to chronic pressure overload, cardiomyocyte-specific apoptosis contributed to the transition from LVH to LVD, and was accompanied by a dramaticCardiomyocytes upregulation of the proapoptotic gene bax and reduced bcl-2/bax ratio, predisposing cardiomers to apoptosis.

Alterations in apoptosis regulatory factors during hypertrophy and heart failure.

It is speculated that this increased sensitivity to apoptotic stimulation along with proapoptotic changes in the apoptosis program may contribute to the development of heart failure seen in pathological cardiac hypertrophy.

Hypertrophy, pathology, and molecular markers of cardiac pathogenesis.

It is determined that hypertrophy is not always associated with increased ventricular expression of ANF and that cells expressing ANF are found in regions of tissue pathology and that alteration in the ventricular Expression of this gene is a sensitive indicator of cardiac pathogenesis.

Myocardial force development and structural changes associated with monocrotaline induced cardiac hypertrophy and heart failure

MCT-induced cardiac hypertrophy and heart failure result in altered cellular calcium handling, depression of maximum force output, an increase in the economy of myocardial contraction and changes in cytoskeletal structure and energy supply.

Ventricular Hypertrophy Plus Neurohumoral Activation Is Necessary to Alter the Cardiac β-Adrenoceptor System in Experimental Heart Failure

Factors that determine β-AR, uptake1, and GRK changes are found and RV weight and RV/left ventricular (LV) weight ratio were significantly increased, whereas plasma noradrenaline, RV β- AR density, RV NAT density and activity, and RV GRK activity were not significantly altered.

Stage-dependent activation of cell cycle and apoptosis mechanisms in the right ventricle by pressure overload.

Ventricular Hypertrophy Plus Neurohumoral Activation Is Necessary to Alter the Cardiac &bgr;-Adrenoceptor System in Experimental Heart Failure

It is concluded that in MCT-treated rats ventricular hypertrophy per se is not sufficient to cause characteristic alterations in the myocardial &bgr;-AR system often seen in heart failure; only if ventricularhypertrophy is associated with neurohumoral activation and GRK activity is increased.

Ventricular adrenomedullin concentration is a sensitive biochemical marker for volume and pressure overload in rats.

The results suggest that the ventricular AM levels are upregulated in both the volume- and pressure-overloaded cardiac hypertrophy by differential transcriptional regulation and that the Ventricular AM may be a biochemical marker for the volume and pressure overload to the ventricle.
...