Myocardial lipid accumulation in patients with pressure-overloaded heart and metabolic syndrome

Raffaele Marfella,Clara Di Filippo,Michele Portoghese,Michelangela Barbieri,Franca Ferraraccio,Mario Siniscalchi,Federico Cacciapuoti,Francesco Rossi,Michele D'Amico,Giuseppe Paolisso

doi:10.1194/jlr.p900032-jlr200

Raffaele Marfella, Clara Di Filippo + Show 8 more

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https://doi.org/10.1194/jlr.p900032-jlr200

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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.

Highlights

We evaluated the role of sterol-regulatory element binding protein (SREBP)-1c/peroxisome proliferator activated receptor-␥ (PPAR␥) pathway on heart lipotoxicity in patients with metabolic syndrome (MS) and aortic stenosis (AS)
Significant differences were found for the components of the MS: body mass index (BMI), waist circumference (WC), fasting insulin, homeostasis model assessment (HOMA) values, glucose, triglyceride, and HDL cholesterol levels
No differences were found in the anthropometric parameters, risks factors, laboratory analysis, and active therapy among the groups of MS patients subdivided on the basis of Ejection fraction (EF) (EF >50%; EF 50% to 30%; EF

Summary

Introduction

We evaluated the role of sterol-regulatory element binding protein (SREBP)-1c/peroxisome proliferator activated receptor-␥ (PPAR␥) pathway on heart lipotoxicity in patients with metabolic syndrome (MS) and aortic stenosis (AS). Patients without MS have low levels and weak immunostaining of SREBP-1c and PPAR␥ in heart specimens. 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 PPAR␥ protein.—Marfella, R., C. Myocardial lipid accumulation in patients with pressure-overloaded heart and metabolic syndrome. Several-fold increased cardiomyocyte triglyceride stores are observed in animal models of obesity and diabetes [4] This lipid accumulation may contribute to cardiomyocyte death by nonoxidative and oxidative [5] metabolic pathways and to HF.

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