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Altered growth-mediated signaling in the hearts of NFATc2 null mice

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Altered growth-mediated signaling in the hearts of NFATc2 null mice

Sin-Chan, Patrick (2011) Altered growth-mediated signaling in the hearts of NFATc2 null mice. Masters thesis, Concordia University.

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Abstract

An abnormality associated with all forms of cardiovascular diseases is cardiac hypertrophy, which is an overall increase in heart mass without improved contractile function. Prolonged cardiac hypertrophy eventually leads to heart failure, in which the heart can no longer supply adequate amounts of blood to meet the body’s hemodynamic demands, resulting in cardiac dilatation, thinning of the myocardial walls, decrease in contractile effectiveness, organ failure and death.

The Ca2+- dependent phosphatase, calcineurin (Cn) and its downstream target, nuclear factor of activated T-cells (NFAT), are major intracellular modulators of cardiac hypertrophy. In young 1-2 month old mice, the NFATc2 transcription factor has been identified as the major NFAT isoform responsible for Cn-mediated cardiac hypertrophy. We observed that adult 6-9 month old NFATc2-/- mice were more prone to sudden death, suggesting that the loss of NFATc2 was detrimental at later stages of life. Using histology, we showed that adult NFATc2-/- mice display left ventricular dilatation and thinning of the ventricular walls, characteristic of failure. Western blot and immunofluorescene results showed that NFATc2-/- mice displayed alterations in the signaling of growth pathways, which predisposed these mice to heart failure. Furthermore, angiotensin II-induced cardiac growth revealed that the hearts of NFATc2-/- mice displayed changes in contractile protein gene expression and an inactivation of both transcriptional and translational mechanisms. Our collective findings propose an uncharacterized role of NFATc2 for normal heart function and biochemical signaling in adult mice, providing further evidence that normal Cn-signaling is crucial in the heart.

Divisions:Concordia University > Faculty of Arts and Science > Chemistry and Biochemistry
Item Type:Thesis (Masters)
Authors:Sin-Chan, Patrick
Institution:Concordia University
Degree Name:M. Sc.
Program:Chemistry
Date:03 January 2011
Thesis Supervisor(s):Michel, Robin
ID Code:7730
Deposited By:PATRICK SIN-CHAN
Deposited On:25 Jul 2011 09:21
Last Modified:16 Dec 2013 11:39

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