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BNP controls early load-dependent regulation of SERCA through calcineurin.

Toischer K, Teucher N, Unsöld B, Kuhn M, Kögler H, Hasenfuss G - Basic Res. Cardiol. (2010)

Bottom Line: Heart failure is characterised by reduced expression of sarcoplasmic reticulum calcium-ATPase (SERCA) and increased expression of B-type natriuretic peptide (BNP).MCIP-mRNA was increased by 333% 6 h after TAC, but not significantly different from sham after 24 h.In conclusion, mechanical load leads to an upregulation of SERCA expression.

View Article: PubMed Central - PubMed

Affiliation: Abteilung Kardiologie und Pneumologie, Georg-August-Universität, Robert-Koch-Str. 40, 37075, Göttingen, Germany.

ABSTRACT
Heart failure is characterised by reduced expression of sarcoplasmic reticulum calcium-ATPase (SERCA) and increased expression of B-type natriuretic peptide (BNP). The present study was performed to investigate causality of this inverse relationship under in vivo conditions in the transversal aortic constriction mouse model (TAC). Left ventricular SERCA-mRNA expression was significantly upregulated in TAC by 32% after 6 h, but not different from sham after 24 h. Serum proANP and BNP levels were increased in TAC after 24 h (BNP +274%, p < 0.01; proANP +60%, p < 0.05), but only proANP levels were increased after 6 h (+182%, p < 0.01). cGMP levels were only increased 24 h after TAC (+307%, p < 0.01), but not 6 h after TAC. BNP infusion inhibited the increase in SERCA expression 6 h after TAC. In BNP-receptor-knockout animals (GC-A), the expression of SERCA was still significantly increased 24 h after TAC at the mRNA level by 35% (p < 0.05), as well as at the protein level by 25% (p < 0.05). MCIP expression as an indicator of calcineurin activity was regulated in parallel to SERCA after 6 and 24 h. MCIP-mRNA was increased by 333% 6 h after TAC, but not significantly different from sham after 24 h. In the GC-A-KO mice, MCIP-mRNA was significantly increased in TAC compared to WT after 24 h. In mice with BNP infusion, MCIP was significantly lower 6 h after TAC compared to control animals. In conclusion, mechanical load leads to an upregulation of SERCA expression. This is followed by upregulation of natriuretic peptides with subsequent suppression of SERCA upregulation. Elevated natriuretic peptides may suppress SERCA expression by inhibition of calcineurin activity via activation of GC-A.

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Source of the natriuretic peptides: expression of BNP (a) and ANP (b) following TAC normalised to sham in the left (LV) and right (RV) ventricle and the left (LA) and the right (RA) atrium 24 h after intervention (per chamber: n = 6/6); *p < 0.05 TAC versus Sham
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Fig3: Source of the natriuretic peptides: expression of BNP (a) and ANP (b) following TAC normalised to sham in the left (LV) and right (RV) ventricle and the left (LA) and the right (RA) atrium 24 h after intervention (per chamber: n = 6/6); *p < 0.05 TAC versus Sham

Mentions: Six hours after TAC, the serum level of ANP (+182%; Fig. 2a), but not BNP (Fig. 2b), was significantly increased compared to control. Serum levels of BNP and pro ANP were elevated 24 h after TAC (proANP: +60%, p < 0.05; BNP: +274%, p < 0.01; Fig. 2c, d). The main source of ANP and BNP 24 h after TAC is the left ventricle (BNP +507% p < 0.05; Fig. 3a). The expression of BNP was paralleled by ANP, only with lower amplitude (Fig. 3b).Fig. 2


BNP controls early load-dependent regulation of SERCA through calcineurin.

Toischer K, Teucher N, Unsöld B, Kuhn M, Kögler H, Hasenfuss G - Basic Res. Cardiol. (2010)

Source of the natriuretic peptides: expression of BNP (a) and ANP (b) following TAC normalised to sham in the left (LV) and right (RV) ventricle and the left (LA) and the right (RA) atrium 24 h after intervention (per chamber: n = 6/6); *p < 0.05 TAC versus Sham
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2965361&req=5

Fig3: Source of the natriuretic peptides: expression of BNP (a) and ANP (b) following TAC normalised to sham in the left (LV) and right (RV) ventricle and the left (LA) and the right (RA) atrium 24 h after intervention (per chamber: n = 6/6); *p < 0.05 TAC versus Sham
Mentions: Six hours after TAC, the serum level of ANP (+182%; Fig. 2a), but not BNP (Fig. 2b), was significantly increased compared to control. Serum levels of BNP and pro ANP were elevated 24 h after TAC (proANP: +60%, p < 0.05; BNP: +274%, p < 0.01; Fig. 2c, d). The main source of ANP and BNP 24 h after TAC is the left ventricle (BNP +507% p < 0.05; Fig. 3a). The expression of BNP was paralleled by ANP, only with lower amplitude (Fig. 3b).Fig. 2

Bottom Line: Heart failure is characterised by reduced expression of sarcoplasmic reticulum calcium-ATPase (SERCA) and increased expression of B-type natriuretic peptide (BNP).MCIP-mRNA was increased by 333% 6 h after TAC, but not significantly different from sham after 24 h.In conclusion, mechanical load leads to an upregulation of SERCA expression.

View Article: PubMed Central - PubMed

Affiliation: Abteilung Kardiologie und Pneumologie, Georg-August-Universität, Robert-Koch-Str. 40, 37075, Göttingen, Germany.

ABSTRACT
Heart failure is characterised by reduced expression of sarcoplasmic reticulum calcium-ATPase (SERCA) and increased expression of B-type natriuretic peptide (BNP). The present study was performed to investigate causality of this inverse relationship under in vivo conditions in the transversal aortic constriction mouse model (TAC). Left ventricular SERCA-mRNA expression was significantly upregulated in TAC by 32% after 6 h, but not different from sham after 24 h. Serum proANP and BNP levels were increased in TAC after 24 h (BNP +274%, p < 0.01; proANP +60%, p < 0.05), but only proANP levels were increased after 6 h (+182%, p < 0.01). cGMP levels were only increased 24 h after TAC (+307%, p < 0.01), but not 6 h after TAC. BNP infusion inhibited the increase in SERCA expression 6 h after TAC. In BNP-receptor-knockout animals (GC-A), the expression of SERCA was still significantly increased 24 h after TAC at the mRNA level by 35% (p < 0.05), as well as at the protein level by 25% (p < 0.05). MCIP expression as an indicator of calcineurin activity was regulated in parallel to SERCA after 6 and 24 h. MCIP-mRNA was increased by 333% 6 h after TAC, but not significantly different from sham after 24 h. In the GC-A-KO mice, MCIP-mRNA was significantly increased in TAC compared to WT after 24 h. In mice with BNP infusion, MCIP was significantly lower 6 h after TAC compared to control animals. In conclusion, mechanical load leads to an upregulation of SERCA expression. This is followed by upregulation of natriuretic peptides with subsequent suppression of SERCA upregulation. Elevated natriuretic peptides may suppress SERCA expression by inhibition of calcineurin activity via activation of GC-A.

Show MeSH
Related in: MedlinePlus