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-γ (PPARγ) 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 PPARγ. Ejection fraction (EF) was lower in MS compared with patients without MS (P 102 cm for men, >88 cm for women; blood pressure elevation >130/85 mm Hg; low HDL cholesterol 150 mg/dl; hyperglycemia, fasting glucose >100 mg/dl. The MS is considered present when at least three of the five traits are present. Among the above patients, 56 presented at least three traits of MS (4 ± 0.8) and 61 without MS (MS-traits: 1.1 ± 0.6). The remaining 165 patients were excluded because of the presence of at least one of the following conditions: diabetes, unstable angina, previous myocardial infarction, coronary stenosis >70%; renal, hepatic, rheumatic, cancerous, or other severe diseases were excluded. Insulin sensitivity was estimated from the homeostasis model assessment (HOMA) (glucose in mmol/L × insulin in µU/ml)/22.5 (13Matthews D.R. Hosker J.P. Rudenski A.S. Naylor B.A. Treacher D.F. Turner R.C. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.Diabetologia. 1985; 28: 412-419Crossref PubMed Scopus (25651) Google Scholar). All patients underwent coronary angiography before valve replacement. On the basis of ejection fraction (EF) determined by echocardiography at the time of admission, MS patients were subdivided into three groups: EF >50% (n = 18); EF 50% to 30% (n = 24); EF 50% (n = (n = <30% (n = ± ± ± ± ± ± ± ± ± ± ± ± HDL ± ± ± ± ± ± ± ± ± ± ± ± parameters valve ± ± ± aortic valve ± ± ± LV mass ± ± ± LV ± ± ± Ejection ± ± ± ± ± ± ± ± ± ± ± ± analysis ± ± ± ± ± ± oil staining ± ± ± SREBP-1c ± ± ± PPARγ ± ± ± are presented as ± or < compared with with ejection fraction < compared with ejection fraction between in a are presented as ± or < compared with with ejection fraction < compared with ejection fraction between All patients of LV hypertrophy (Table 1). LV function was impaired in MS MS patients lower EF and higher (P < 1). difference in the aortic orifice surface among the was found (Table 1). Moreover, MS patients EF not with aortic orifice surface = = whereas a correlation between aortic orifice surface and EF = < in patients without MS was We not in ventricular This was by of an gene that the was in ventricular biopsies from patients 1). Moreover, the staining of lipid accumulation in However, H and E staining of heart specimens from MS patients revealed with intracellular accumulation of lipid red O staining high lipid in myocytes of MS patients (Table 1). We detected myocytes and of lipid in of 56 specimens from MS patients, whereas the myocardial alterations were not detected in biopsies from patients without MS. Moreover, content was higher in specimens from MS patients in specimens of patients without MS (Table 1). Moreover, we observed that myocytes and myocytes with lipid increased with EF A correlation between and of the myocytes was observed = < analysis revealed that and triglycerides were both of myocardial lipid content = < = < whereas and were to myocardial triglyceride myocytes in specimens and The from a without metabolic syndrome myocytes without The specimens from a with metabolic syndrome a high of myocytes from patients with metabolic syndrome a increase in myocytes to the ejection fraction and the of the analysis of PPARγ and mRNA levels from ventricular specimens from the of patients. In patients without cardiac PPARγ and were not or were detected In contrast, higher levels of PPARγ and were seen in from the MS patients as as strong immunostaining for PPARγ was a correlation between PPARγ and SREBP-1c protein levels = < 0.001). The and plasma triglycerides were with SREBP-1c protein levels = < = < 0.001). analysis revealed that triglycerides and were both of myocardial SREBP-1c = < = < as as PPARγ = < = < whereas and were to PPARγ Moreover, was a correlation between PPARγ protein levels and EF = < = < in heart specimens from patients with MS correlation was observed between PPARγ and EF in patients without MS = = = = immunohistochemical analysis of PPARγ protein from ventricular specimens The from a without metabolic syndrome not immunostaining for PPARγ protein in The from a with metabolic syndrome a strong immunostaining for PPARγ protein in myocytes as as in myocytes in which the staining is the from patients with metabolic syndrome a increase in both myocytes and for PPARγ protein to the ejection fraction Western analysis of PPARγ protein in heart specimens from patients with metabolic syndrome to the ejection < patients with ejection fraction between 30% and < patients with ejection fraction < patients without metabolic analysis of PPARγ protein content in heart specimens from patients with metabolic syndrome to the ejection fraction PPARγ mRNA levels in ventricular biopsies from patients without metabolic syndrome and from patients with metabolic syndrome to ejection The mRNA levels were with analysis of PPARγ mRNA content in heart specimens from patients without metabolic syndrome and from patients with metabolic syndrome to the ejection fraction levels and immunostaining of and were seen in from patients with and without MS. were no among the groups. The level of protein is 30% lower in heart specimens from patients with MS compared with heart specimens from patients without MS (Table 1). Moreover, a correlation between levels and of the myocytes was observed = < of were higher in heart specimens from MS patients compared with specimens from patients without MS ± ± < 0.001). immunostaining for the was were found between tissues from patients with and without MS. immunostaining was present in from MS patients compared with tissues from patients without MS ± ± < Moreover, a correlation between levels and of the myocytes was observed = < The of was to the myocyte lipid accumulation with the expression of SREBP-1c and PPARγ in patients with MS undergoing aortic valve replacement. We evidence that MS is strongly associated with cardiac in patients with MS patients present EF and impaired compared with patients without MS. Moreover, we observed that the levels of protein are 30% lower in heart specimens from patients with MS compared with heart specimens from patients without MS. This is in with human that concentrations are D. gene expression of a human J. 2002; Full Text Full Text PDF PubMed Scopus Google Scholar). in metabolic in and in by metabolic alterations a cardiac to direct in heart function of disease M.E. P. Taegtmeyer H. and of the heart in Part 2002; PubMed Scopus Google Scholar). with into the during and of levels is an important to dysfunction in the presence of the metabolic alterations M.E. P. Taegtmeyer H. and of the heart in Part 2002; PubMed Scopus Google Scholar). In MS patients, we evidenced that a strong correlation also between the progression of cardiac dysfunction and myocytes lipid accumulation with of myocytes and oil red O and EF are and cause LV and HF in patients with AS and MS. In this the EF was to the aortic stenosis in patients, whereas a correlation between cardiac function and myocardial in patients with AS and MS because the cardiac were from the stenosis and were associated with a marked cardiomyocyte lipid accumulation. it is metabolic of MS cardiac lipid evidence suggests that excess is associated with gene expression G. G. M. N. M. P. H. lipid accumulation and SREBP-1c expression are to insulin resistance and in Full Text Full Text PDF PubMed Scopus Google Scholar). Regulation of gene expression by in is an important to to the The metabolic the of and 2005; PubMed Scopus Google Scholar). models have that the transcription of for and in liver is by SREBP-1c is a transcription factor that controls lipogenesis and is induced during overnutrition to facilitate the conversion of glucose to fatty acids and triglycerides for the storage of the excess energy (8Tontonoz P. Kim J.B. Graves R.A. Spiegelman B.M. 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