|
| Status |
Public on Oct 10, 2012 |
| Title |
Loss of heat shock protein HSPA4 aggravates pressure overload-induced myocardial damage |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Failure of molecular chaperones to direct the correct folding of newly synthesized proteins leads to the accumulation of misfolded proteins in cells. HSPA4 is a member of the heat shock protein 110 family (HSP110) that acts as a nucleotide exchange factor of HSP70 chaperones. We found that the expression of HSPA4 is upregulated in murine hearts subjected to pressure overload and in failing human hearts. To investigate the cardiac function of HSPA4, Hspa4 knockout (KO) mice were generated and exhibited cardiac hypertrophy and fibrosis. Hspa4 KO hearts were characterized by a significant increase in heart weight/body weight ratio, elevated expression of hypertrophic and fibrotic gene markers, and concentric hypertrophy with preserved contractile functions. Cardiac hypertrophy in Hspa4 KO hearts was associated with enhanced activation of gp130-STAT3, CaMKII, and calcineurin-NFAT signaling. Further analyses revealed a significant increase in cross sectional area of cardiomyocytes, and in expression levels of hypertrophic markers in cultured neonatal Hspa4 KO cardiomyocytes suggesting that the hypertrophy of mutant mice was a result of primary defects in cardiomyocytes. Gene expression profile in hearts of 3.5-week-old mice revealed a differentially expressed gene sets related to ion channels and stress response. Taken together, these results reveal that HSPA4 is implicated in protection against pressure overload-induced heart failure.
|
| |
|
| Overall design |
Total RNA was extracted from heart ventricles of 3.5-week-old Hspa4+/+ and Hspa4-/- males (n = 3 mice for each genotype).
|
| |
|
| Contributor(s) |
Mohamed B, Barakat A, Zimmermann W, Bittner R, Mühlfeld C, Hünlich M, Engel W, Maier LS, Adham I |
| Citation(s) |
22884543 |
| |
| Submission date |
Oct 11, 2011 |
| Last update date |
May 12, 2015 |
| Contact name |
belal Awd Mohamed |
| E-mail(s) |
[email protected]
|
| Organization name |
Medical university, Goettingen
|
| Department |
Institute of Human Genetics
|
| Lab |
108
|
| Street address |
Heinrich Dueker Weg 12
|
| City |
Goettingen |
| State/province |
Lower Saxony |
| ZIP/Postal code |
37073 |
| Country |
Germany |
| |
|
| Platforms (1) |
| GPL13730 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [CDF: MoGene10stv1_Mm_ENTREZG_14.1.0] |
|
| Samples (6)
|
|
| Relations |
| BioProject |
PRJNA146617 |
Less...
More...