Carregant...
Fitxers
Tipus de document
ArticleVersió
Versió publicadaData de publicació
Llicència de publicació
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/124685
Increased expression of fatty-acid and calcium metabolism genes in failing human heart.
Títol de la revista
Director/Tutor
ISSN de la revista
Títol del volum
Recurs relacionat
Resum
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-(Ca2+)-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 Ca2+-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 Ca2+-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. Ca2+-handling genes TPCN1 and TPCN2 also showed increased expression in HF, while HF- and CM-specific positive correlations were found among several FA and Ca2+-handling genes.
Matèries (anglès)
Citació
Col·leccions
Citació
GARCÍA RÚA, Vanessa, FRANCISCO OTERO, Manuel, LEAR, Pamela virginia, RODRÍGUEZ PENAS, Diego, FEIJÓO BANDÍN, Sandra, NOGUERA MORENO, Teresa, CALAZA, Manuel, ÁLVAREZ BARREDO, María, MOSQUERA LEAL, Ana, PARRINGTON, John, BRUGADA TERRADELLAS, Josep, PORTOLÉS, Manuel, RIVERA, Miguel, GONZÁLEZ-JUANATEY, José r., LAGO, Francisca. Increased expression of fatty-acid and calcium metabolism genes in failing human heart.. _PLoS One_. 2012. Vol. 7, núm. 6, pàgs. e37505. [consulta: 20 de gener de 2026]. ISSN: 1932-6203. [Disponible a: https://hdl.handle.net/2445/124685]