Myocardial lipid accumulation in patients with pressure-overloaded heart and metabolic syndrome.
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.
Marfella
Raffaele
R
Department of Geriatrics and Metabolic Diseases, Second University of Naples, Italy. raffaele.marfella@unina2.it
Di Filippo
Clara
C
Portoghese
Michele
M
Barbieri
Michelangela
M
Ferraraccio
Franca
F
Siniscalchi
Mario
M
Cacciapuoti
Federico
F
Rossi
Francesco
F
D'Amico
Michele
M
Paolisso
Giuseppe
G
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
D008055:Lipids; D047495:PPAR gamma; D051780:Sterol Regulatory Element Binding Protein 1