In:
American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 300, No. 3 ( 2011-03), p. H943-H950
Abstract:
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/d t max , and dP/d t 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.
Type of Medium:
Online Resource
ISSN:
0363-6135
,
1522-1539
DOI:
10.1152/ajpheart.00490.2010
Language:
English
Publisher:
American Physiological Society
Publication Date:
2011
detail.hit.zdb_id:
1477308-9
SSG:
12
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