Vascular Effects of Diet Supplementation With Plant Sterols
Oliver Weingärtner, MD*,
Dieter Lütjohann, PhD ,
Shengbo Ji||,
Nicole Weisshoff*,
Franka List*,
Thomas Sudhop, MD ,
Klaus von Bergmann, MD,
Karen Gertz, MD||,
Jochem König, PhD¶,
Hans-Joachim Schäfers, MD ,
Matthias Endres, MD||,
Michael Böhm, MD* and
Ulrich Laufs, MD*,*
* Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany
Klinik für Thorax- und Herz-Gefäßchirurgie, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany
Institut für Klinische Chemie und Pharmakologie, Universitätsklinikum Bonn, Germany
Abteilung für Klinische Pharmakologie, Universitätsklinikum Bonn, Germany
|| Klinik und Poliklinik für Neurologie, Charité Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany
¶ Institut für Medizinische Biometrie, Epidemiologie und Informatik, Johannes Gutenberg-Universität Mainz, Germany.
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Figure 1 Effects of Plant Sterols on Endothelial Function and Cerebral Ischemia in Wild-Type Mice
Effect of a 4-week treatment of wild-type mice with normal chow (NC) and NC supplemented with plant sterol ester (PSE). (A) Plasma cholesterol, (B) campesterol, and (C) sitosterol concentrations determined by gas liquid chromatography-mass spectrometry; n = 10/group. Aortic segments were isolated, and their functional performance was assessed in organ chamber experiments. (D) Endothelium-dependent vasorelaxation induced by carbachol and (E) endothelium-independent vasodilation induced by nitroglycerin (NTG), expressed in percent of maximal phenylephrine-induced vasoconstriction; n = 10/group. Effects of NC + PSE compared with NC on ischemic stroke. Mice were subjected to 30-min filamentous middle cerebral artery occlusion and 72 h reperfusion. (F) Representative examples of 20-µm coronal brain cryostat sections, (G) indirect cerebral lesion volumes, and (H) direct cerebral lesion areas determined on 5 coronal brain sections (2 mm distance from frontal pole) by computer-assisted volumetry; n = 8/group. Values are mean ± SEM; *p < 0.05, **p < 0.01.
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Figure 2 Effects of Plant Sterols on Plasma Cholesterol, Sitosterol, and Campesterol in ApoE–/– Mice
Effect of 6-month treatment of apolipoprotein E (ApoE)–/– mice with a high-cholesterol Western-type diet (WTD) or NC supplemented with PSE, ezetimibe (EZE), and their combination (PSE + EZE) on plasma cholesterol, sitosterol, and campesterol concentrations determined by gas liquid chromatography-mass spectrometry. Values are mean ± SEM (n = 10/group). (A) #p < 0.05 for WTD versus WTD + PSE, WTD + EZE, and WTD + PSE + EZE. p < 0.05 for WTD + EZE versus WTD + PSE + EZE. *p < 0.05 for WTD + PSE versus WTD, WTD + EZE, and WTD + PSE + EZE. (B) #p < 0.05 for NC versus NC + PSE, NC + EZE, and NC + PSE + EZE. *p < 0.05 for NC, NC + PSE versus NC + EZE, and NC + PSE + EZE. Abbreviations as in Figure 1.
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Figure 3 Effects of Plant Sterols on Atherosclerotic Lesions in ApoE–/– Mice
Atherosclerotic lesion formation was quantitated in the aortic sinus of ApoE–/– mice treated with high-cholesterol WTD or NC supplemented with PSE, EZE, and their combination (PSE + EZE). (A and B) Representative examples, and (C and D) histomorphologic analysis. #p < 0.05 compared with WTD or NC; *p < 0.05 for WTD + EZE versus WTD + PSE or NC + EZE versus NC + PSE; values are mean ± SEM (n = 10/group). Abbreviations as in Figures 1 and 2.
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Figure 4 Histological Characterization of Atherosclerotic Lesions in ApoE–/– Mice
Representative atherosclerotic lesions from ApoE–/– mice treated with high-cholesterol WTD or NC supplemented with PSE, EZE, and their combination (PSE + EZE) stained for (A) oil red O (ORO), (B) collagen (picrosirius red), (C) macrophages (MAC, MOMO-2), and (D) vascular smooth muscle cells (SMC alpha-actin). (E) Semiquantitative grading of stainings: (+) weak staining, (++) moderate staining, (+++) intense staining. I = intima; L = lumen; M = media; other abbreviations as in Figures 1 and 2.
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Figure 5 Effect of Diet Supplementation on Plant Sterol Concentrations in Plasma and Aortic Valves in Humans
Plasma and tissue analysis of cholesterol and plant sterol concentrations in 82 consecutive patients undergoing elective aortic valve surgery determined by gas liquid chromatography-mass spectrometry. (A) Correlation of sitosterol to campesterol in aortic valve cusps (r = 0.98; p < 0.0001). (B) Correlation of campesterol to cholesterol ratios between plasma and aortic valves (r = 0.76; p < 0.0001). Concentrations of sitosterol and campesterol in aortic valve cusps of patients using sterol ester–enriched margarine: open circles = no intake of sterol ester–enriched margarine (n = 72); solid circles = irregular intake of sterol ester–enriched margarine (n = 4); solid squares = regular intake of sterol ester–enriched margarine (n = 6). Effect of frequency of sterol-enriched margarine consumption on (C) plasma and (D) aortic valve tissue campesterol concentrations and campesterol to cholesterol ratios in plasma and tissue (E and F). *p < 0.01 compared with "no use." Values are mean ± SEM.
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Figure 6 Effects of Statin Treatment and Family History of Cardiovascular Diseases
(A) Effect of statin treatment (n = 32/72) on campesterol and the cholesterol precursor lathosterol in relation to cholesterol in plasma and in aortic valve cusps; *p < 0.05. Values are mean ± SEM. (B) Effect of a positive (pos) family history of cardiovascular diseases (n = 15) on campesterol and lathosterol in relation to cholesterol in plasma and in aortic valve cusps in patients without statin treatment and consumption of plant sterol ester (PSE)-enriched food (n = 40). Neg = negative.
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