RGD Reference Report - Decreased cardiac SERCA2 expression, SR Ca uptake, and contractile function in hypothyroidism are attenuated in SERCA2 overexpressing transgenic rats. - Rat Genome Database

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Decreased cardiac SERCA2 expression, SR Ca uptake, and contractile function in hypothyroidism are attenuated in SERCA2 overexpressing transgenic rats.

Authors: Vetter, R  Rehfeld, U  Reissfelder, C  Fechner, H  Seppet, E  Kreutz, R 
Citation: Vetter R, etal., Am J Physiol Heart Circ Physiol. 2011 Mar;300(3):H943-50. Epub 2011 Jan 7.
RGD ID: 6904140
Pubmed: PMID:21217071   (View Abstract at PubMed)
PMCID: PMC3302195   (View Article at PubMed Central)
DOI: DOI:10.1152/ajpheart.00490.2010   (Journal Full-text)

The sarco/endoplasmic reticulum (SR) Ca(2+)-ATPase SERCA2a has a key role in controlling cardiac contraction and relaxation. In hypothyroidism, decreased expression of the thyroid hormone (TH)-responsive SERCA2 gene contributes to slowed SR Ca(2+) reuptake and relaxation. We investigated whether cardiac expression of a TH-insensitive SERCA2a cDNA minigene can rescue SR Ca(2+) handling and contractile function in female SERCA2a-transgenic rats (TG) with experimental hypothyroidism. Wild-type rats (WT) and TG were rendered hypothyroid by 6-N-propyl-2-thiouracil treatment for 6 wk; control rats received no treatment. In vivo measured left ventricular (LV) hemodynamic parameters were compared with SERCA2a expression and function in LV tissue. Hypothyroidism decreased LV peak systolic pressure, dP/dt(max), and dP/dt(min) in both WT and TG. However, loss of function was less in TG. Thus slowed relaxation in hypothyroidism was found to be 1.5-fold faster in TG compared with WT (P < 0.05). In parallel, a 1.4-fold higher V(max) value of homogenate SR Ca(2+) uptake was observed in hypothyroid TG (P < 0.05 vs. hypothyroid WT), and the hypothyroidism-caused decline of LV SERCA2a mRNA expression in TG by -24% was markedly less than the decrease of -49% in WT (P < 0.05). A linear relationship was observed between the SERCA2a/PLB mRNA ratio values and the V(max) values of SR Ca(2+) uptake when the respective data of all experimental groups were plotted together (r = 0.90). The data show that expression of the TH-insensitive SERCA2a minigene compensates for loss of expressional activity of the TH-responsive native SERCA2a gene in the female hypothyroid rat heart. However, SR Ca(2+) uptake and in vivo heart function were only partially rescued.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ATP2A2Humanhypothyroidism  ISOAtp2a2 (Rattus norvegicus)mRNA:decreased expression:heart left ventricleRGD 
Atp2a2Rathypothyroidism  IEP mRNA:decreased expression:heart left ventricleRGD 
Atp2a2Mousehypothyroidism  ISOAtp2a2 (Rattus norvegicus)mRNA:decreased expression:heart left ventricleRGD 

Objects Annotated

Genes (Rattus norvegicus)
Atp2a2  (ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2)

Genes (Mus musculus)
Atp2a2  (ATPase, Ca++ transporting, cardiac muscle, slow twitch 2)

Genes (Homo sapiens)
ATP2A2  (ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2)


Additional Information