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Increased expression of fatty-acid and calcium metabolism genes in failing human heart.

García-Rúa V, Otero MF, Lear PV, Rodríguez-Penas D, Feijóo-Bandín S, Noguera-Moreno T, Calaza M, Álvarez-Barredo M, Mosquera-Leal A, Parrington J, Brugada J, Portolés M, Rivera M, González-Juanatey JR, Lago F - PLoS ONE (2012)

Bottom Line: In ICM there were six correlations, all distinct from those found in CTL.DCM-specific increases were found in expression of several genes that regulate FA metabolism, which might help in the design of aetiology-specific metabolic therapies in HF.Ca(2+)-handling genes TPCN1 and TPCN2 also showed increased expression in HF, while HF- and CM-specific positive correlations were found among several FA and Ca(2+)-handling genes.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cellular and Molecular Cardiology, Santiago Institute of Biomedical Research (IDIS), University of Santiago de Compostela Clinical Hospital (CHUS), Santiago de Compostela, Spain.

ABSTRACT

Background: Heart failure (HF) involves alterations in metabolism, but little is known about cardiomyopathy-(CM)-specific or diabetes-independent alterations in gene expression of proteins involved in fatty-acid (FA) uptake and oxidation or in calcium-(Ca(2+))-handling in the human heart.

Methods: RT-qPCR was used to quantify mRNA expression and immunoblotting to confirm protein expression in left-ventricular myocardium from patients with HF (n = 36) without diabetes mellitus of ischaemic (ICM, n = 16) or dilated (DCM, n = 20) cardiomyopathy aetiology, and non-diseased donors (CTL, n = 6).

Results: Significant increases in mRNA of genes regulating FA uptake (CD36) and intracellular transport (Heart-FA-Binding Protein (HFABP)) were observed in HF patients vs CTL. Significance was maintained in DCM and confirmed at protein level, but not in ICM. mRNA was higher in DCM than ICM for peroxisome-proliferator-activated-receptor-alpha (PPARA), PPAR-gamma coactivator-1-alpha (PGC1A) and CD36, and confirmed at the protein level for PPARA and CD36. Transcript and protein expression of Ca(2+)-handling genes (Two-Pore-Channel 1 (TPCN1), Two-Pore-Channel 2 (TPCN2), and Inositol 1,4,5-triphosphate Receptor type-1 (IP3R1)) increased in HF patients relative to CTL. Increases remained significant for TPCN2 in all groups but for TPCN1 only in DCM. There were correlations between FA metabolism and Ca(2+)-handling genes expression. In ICM there were six correlations, all distinct from those found in CTL. In DCM there were also six (all also different from those found in CTL): three were common to and three distinct from ICM.

Conclusion: DCM-specific increases were found in expression of several genes that regulate FA metabolism, which might help in the design of aetiology-specific metabolic therapies in HF. Ca(2+)-handling genes TPCN1 and TPCN2 also showed increased expression in HF, while HF- and CM-specific positive correlations were found among several FA and Ca(2+)-handling genes.

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Increased human myocardial expression of Two-Pore Calcium channels TPCN1 and TPCN2 in heart failure as a whole (HF) and aetiological groups (ischaemic or dilated cardiomyopathy, ICM, DCM) and compared with non-diseased donors (CTL).A. Box-plot of TPCN1 and TPCN2 mRNA expression, showing for TPCN1 a significant increase over CTL (n = 6) for HF (n = 36, p = 0.018) and DCM (n = 20, p = 0.015); and for TPCN2 a significant increase over CTL (n = 6) for HF (n = 36, p = 0.001), ICM (n = 16, p = 0.008) and DCM (n = 20, p = 0.001). B. Densitometry analysis and representative immunoblot of TPCN1 protein expression showing a significant increase over CTL (n = 4) for DCM (n = 13, p = 0.002). C. Densitometry analysis and representative immunoblot of TPCN2 protein expression showing a significant increase over CTL (n = 4) for both ICM (n = 8, p = 0.016) and DCM (n = 6, p = 0.031). (a.u.: arbitrary units).
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pone-0037505-g003: Increased human myocardial expression of Two-Pore Calcium channels TPCN1 and TPCN2 in heart failure as a whole (HF) and aetiological groups (ischaemic or dilated cardiomyopathy, ICM, DCM) and compared with non-diseased donors (CTL).A. Box-plot of TPCN1 and TPCN2 mRNA expression, showing for TPCN1 a significant increase over CTL (n = 6) for HF (n = 36, p = 0.018) and DCM (n = 20, p = 0.015); and for TPCN2 a significant increase over CTL (n = 6) for HF (n = 36, p = 0.001), ICM (n = 16, p = 0.008) and DCM (n = 20, p = 0.001). B. Densitometry analysis and representative immunoblot of TPCN1 protein expression showing a significant increase over CTL (n = 4) for DCM (n = 13, p = 0.002). C. Densitometry analysis and representative immunoblot of TPCN2 protein expression showing a significant increase over CTL (n = 4) for both ICM (n = 8, p = 0.016) and DCM (n = 6, p = 0.031). (a.u.: arbitrary units).

Mentions: In HF (n = 36) as a whole, mRNA expression for TPCN1 (p = 0.018), TPCN2 (p = 0.001) and IP3R1 (p = 0.035) was also increased relative to CTL (Table 3 and Figs. 3 and 4).


Increased expression of fatty-acid and calcium metabolism genes in failing human heart.

García-Rúa V, Otero MF, Lear PV, Rodríguez-Penas D, Feijóo-Bandín S, Noguera-Moreno T, Calaza M, Álvarez-Barredo M, Mosquera-Leal A, Parrington J, Brugada J, Portolés M, Rivera M, González-Juanatey JR, Lago F - PLoS ONE (2012)

Increased human myocardial expression of Two-Pore Calcium channels TPCN1 and TPCN2 in heart failure as a whole (HF) and aetiological groups (ischaemic or dilated cardiomyopathy, ICM, DCM) and compared with non-diseased donors (CTL).A. Box-plot of TPCN1 and TPCN2 mRNA expression, showing for TPCN1 a significant increase over CTL (n = 6) for HF (n = 36, p = 0.018) and DCM (n = 20, p = 0.015); and for TPCN2 a significant increase over CTL (n = 6) for HF (n = 36, p = 0.001), ICM (n = 16, p = 0.008) and DCM (n = 20, p = 0.001). B. Densitometry analysis and representative immunoblot of TPCN1 protein expression showing a significant increase over CTL (n = 4) for DCM (n = 13, p = 0.002). C. Densitometry analysis and representative immunoblot of TPCN2 protein expression showing a significant increase over CTL (n = 4) for both ICM (n = 8, p = 0.016) and DCM (n = 6, p = 0.031). (a.u.: arbitrary units).
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Related In: Results  -  Collection

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pone-0037505-g003: Increased human myocardial expression of Two-Pore Calcium channels TPCN1 and TPCN2 in heart failure as a whole (HF) and aetiological groups (ischaemic or dilated cardiomyopathy, ICM, DCM) and compared with non-diseased donors (CTL).A. Box-plot of TPCN1 and TPCN2 mRNA expression, showing for TPCN1 a significant increase over CTL (n = 6) for HF (n = 36, p = 0.018) and DCM (n = 20, p = 0.015); and for TPCN2 a significant increase over CTL (n = 6) for HF (n = 36, p = 0.001), ICM (n = 16, p = 0.008) and DCM (n = 20, p = 0.001). B. Densitometry analysis and representative immunoblot of TPCN1 protein expression showing a significant increase over CTL (n = 4) for DCM (n = 13, p = 0.002). C. Densitometry analysis and representative immunoblot of TPCN2 protein expression showing a significant increase over CTL (n = 4) for both ICM (n = 8, p = 0.016) and DCM (n = 6, p = 0.031). (a.u.: arbitrary units).
Mentions: In HF (n = 36) as a whole, mRNA expression for TPCN1 (p = 0.018), TPCN2 (p = 0.001) and IP3R1 (p = 0.035) was also increased relative to CTL (Table 3 and Figs. 3 and 4).

Bottom Line: In ICM there were six correlations, all distinct from those found in CTL.DCM-specific increases were found in expression of several genes that regulate FA metabolism, which might help in the design of aetiology-specific metabolic therapies in HF.Ca(2+)-handling genes TPCN1 and TPCN2 also showed increased expression in HF, while HF- and CM-specific positive correlations were found among several FA and Ca(2+)-handling genes.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cellular and Molecular Cardiology, Santiago Institute of Biomedical Research (IDIS), University of Santiago de Compostela Clinical Hospital (CHUS), Santiago de Compostela, Spain.

ABSTRACT

Background: Heart failure (HF) involves alterations in metabolism, but little is known about cardiomyopathy-(CM)-specific or diabetes-independent alterations in gene expression of proteins involved in fatty-acid (FA) uptake and oxidation or in calcium-(Ca(2+))-handling in the human heart.

Methods: RT-qPCR was used to quantify mRNA expression and immunoblotting to confirm protein expression in left-ventricular myocardium from patients with HF (n = 36) without diabetes mellitus of ischaemic (ICM, n = 16) or dilated (DCM, n = 20) cardiomyopathy aetiology, and non-diseased donors (CTL, n = 6).

Results: Significant increases in mRNA of genes regulating FA uptake (CD36) and intracellular transport (Heart-FA-Binding Protein (HFABP)) were observed in HF patients vs CTL. Significance was maintained in DCM and confirmed at protein level, but not in ICM. mRNA was higher in DCM than ICM for peroxisome-proliferator-activated-receptor-alpha (PPARA), PPAR-gamma coactivator-1-alpha (PGC1A) and CD36, and confirmed at the protein level for PPARA and CD36. Transcript and protein expression of Ca(2+)-handling genes (Two-Pore-Channel 1 (TPCN1), Two-Pore-Channel 2 (TPCN2), and Inositol 1,4,5-triphosphate Receptor type-1 (IP3R1)) increased in HF patients relative to CTL. Increases remained significant for TPCN2 in all groups but for TPCN1 only in DCM. There were correlations between FA metabolism and Ca(2+)-handling genes expression. In ICM there were six correlations, all distinct from those found in CTL. In DCM there were also six (all also different from those found in CTL): three were common to and three distinct from ICM.

Conclusion: DCM-specific increases were found in expression of several genes that regulate FA metabolism, which might help in the design of aetiology-specific metabolic therapies in HF. Ca(2+)-handling genes TPCN1 and TPCN2 also showed increased expression in HF, while HF- and CM-specific positive correlations were found among several FA and Ca(2+)-handling genes.

Show MeSH
Related in: MedlinePlus