title: Myocardial lipid accumulation in patients with pressure-overloaded heart and metabolic syndrome.
abstract: We evaluated the role of sterol-regulatory element binding protein (SREBP)-1c/peroxisome proliferator activated receptor-gamma (PPARgamma) pathway on heart lipotoxicity in patients with metabolic syndrome (MS) and aortic stenosis (AS). Echocardiographic parameters of heart function and structural alterations of LV specimens were studied in patients with (n = 56) and without (n = 61) MS undergoing aortic valve replacement. Tissues were stained with hematoxylin-eosin (H and E) and oil red O for evidence of intramyocyte lipid accumulation. The specimens were also analyzed with PCR, Western blot, and immunohistochemical analysis for SREBP-1c and PPARgamma. Ejection fraction (EF) was lower in MS compared with patients without MS (P < 0.001); no difference was found in aortic orifice surface among the groups. H and E and oil red O staining of specimens from MS patients revealed several myocytes with intracellular accumulation of lipid, whereas these alterations were not detected in biopsies from patients without MS. Patients without MS have low levels and weak immunostaining of SREBP-1c and PPARgamma in heart specimens. In contrast, strong immunostaining and higher levels of SREBP-1c and PPARgamma were seen in biopsies from the MS patients. Moreover, we evidenced a significative correlation between both SREBP-1c and PPARgamma and EF and intramyocyte lipid accumulation (P < 0.001). SREBP-1c may contribute to heart dysfunction by promoting lipid accumulation within myocytes in MS patients with AS; SREBP-1c may do it by increasing the levels of PPARgamma protein.
authors.affiliation: Department of Geriatrics and Metabolic Diseases, Second University of Naples, Italy. raffaele.marfella@unina2.it
authors.forename: Raffaele
authors.initials: R
authors.lastname: Marfella
authors.forename: Clara
authors.initials: C
authors.lastname: Di Filippo
authors.forename: Michele
authors.initials: M
authors.lastname: Portoghese
authors.forename: Michelangela
authors.initials: M
authors.lastname: Barbieri
authors.forename: Franca
authors.initials: F
authors.lastname: Ferraraccio
authors.forename: Mario
authors.initials: M
authors.lastname: Siniscalchi
authors.forename: Federico
authors.initials: F
authors.lastname: Cacciapuoti
authors.forename: Francesco
authors.initials: F
authors.lastname: Rossi
authors.forename: Michele
authors.initials: M
authors.lastname: D'Amico
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Paolisso
mesh_terms: D000368:Aged; D001024:Aortic Valve Stenosis / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D004452:Echocardiography / Q000379:methods; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D050356:Lipid Metabolism; D008055:Lipids / Q000032:analysis*; D008297:Male; D024821:Metabolic Syndrome / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D008055:Lipids; D047495:PPAR gamma; D051780:Sterol Regulatory Element Binding Protein 1