Increased Plasma 7β-Hydroxycholesterol Concentrations in a Population With a High Risk for Cardiovascular Disease

Abstract

Abstract-The mortality in coronary heart disease among 50-to 54-year-old men is 4 times higher in Lithuania than in Sweden. It was recently suggested that traditional risk factors could not explain this mortality difference. LDL of Lithuanian men showed, however, a lower resistance to oxidation than that of Swedish men. In addition, the plasma concentration of ␥-tocopherol, lycopene, and ␤-carotene were lower in Lithuanian men. In the present investigation, we determined plasma oxysterols in men from Lithuania and Sweden and found that the plasma concentration of 7␤-hydroxycholesterol was higher in Lithuanian men, 12Ϯ5 versus 9Ϯ8 (SD) ng/mL (Pϭ0.0011). This oxysterol is a cholesterol autoxidation product and there is no indication that it should have an enzymatic origin. Mean LDL oxidation lag time was shorter in Lithuanian men (75Ϯ14 versus 90Ϯ13 minutes, PϽ0.0001) and the concentration of LDL linoleic acid was lower (249Ϯ56 versus 292Ϯ54 g/mg of LDL protein, PϽ0.0001). Lipid corrected ␥-tocopherol was 0.07Ϯ0.02 mg/mL in Vilnius men and 0.12Ϯ0.04 mg/mL (PϽ0.0001) in Linköping men. There was a negative correlation between the concentration of 7␤-hydroxycholesterol and lag time (RϭϪ0.31, Pϭ0.0023). It is suggested that the higher 7␤-hydroxycholesterol concentration in Lithuanian men is an indication of an increased in vivo lipid peroxidation. (Arterioscler Thromb Vasc Biol. 1999;19:967-971.)Key Words: oxysterols Ⅲ LDL oxidation Ⅲ vitamins Ⅲ fatty acids Ⅲ cross-sectional study C oronary heart disease (CHD) incidence and mortality is rising in the East European countries, in contrast to the decreasing trend in Western Europe and in the United States. [1][2][3] For example, the mortality in CHD among 50-to 54-year-old men was 4 times higher in Lithuania than in Sweden in 1994. In LiVicordia I, a cross-sectional population study, we investigated the prevalence of ultrasound-detected subclinical atherosclerosis and possible causes for these diverging coronary mortality trends in the 2 countries. 4 Lithuanian men had more carotid atherosclerosis. Although traditional risk factors could not explain the difference in CHD mortality, we found that Lithuanian men had a higher LDL susceptibility to oxidation and lower concentrations of the plasma antioxidant vitamins ␥-tocopherol, ␤-carotene, and lycopene than Swedish men. There is a high correlation between the plasma concentrations of these vitamins and the corresponding vitamin content in LDL. 5 The increased susceptibility to oxidation and lower concentrations of LDLassociated vitamins in the Lithuanian population may be caused by dietary factors or an increased in vivo oxidation of LDL. We have recently shown that cholesterol oxidation products (oxysterols) are good markers of LDL oxidation in vitro. 6 In addition, the oxysterol 7␤-hydroxycholesterol, together with an increased oxidation susceptibility of VLDLϩLDL, were the strongest predictors of progression of carotid atherosclerosis in Finnish men. 7 We therefore decided to determine oxysterols in plasma from the 2 p...

Oxidation as a crucial reaction for cholesterol to induce tissue degeneration: CD36 overexpression in human promonocytic cells treated with a biologically relevant oxysterol mixture

“…Of note, the oxysterol mixture employed (2 × 10 -5 M) is representative of oxysterol concentration present in vascular lesions (Leonarduzzi et al, 2007) while it is detectable in low concentration in oxLDL (i.e. within 10 -7 -10 -8 M range) (Ziedén et al, 1999).…”

“…In relation to this, a pathophysiologically relevant concentration of oxysterols has been consistently detected in the plasma of hypercholesterolemic subjects and in human atherosclerotic lesions (Brown & Jessup, 1999;Ziedén et al ., 1999;Schroepfer, 2000;Iuliano et al ., 2003;Leonarduzzi et al ., 2007). These compounds, of both dietary and metabolic origin, are known to exert a large variety of biochemical activities (Brown & Jessup, 1999;Leonarduzzi et al ., 2002), and their potential role in the pathogenesis of age-related diseases, proposed more than a decade ago, is now receiving more appropriate attention (Leonarduzzi et al ., 2005a,b;Vaya & Schipper, 2007).…”

Long-Term Effects of Vitamin E, Vitamin C, and Combined Supplementation on Urinary 7-Hydro-8-Oxo-2′-Deoxyguanosine, Serum Cholesterol Oxidation Products, and Oxidation Resistance of Lipids in Nondepleted Men

“…[23][24][25][26][27][28][29] Moreover, the major products of cholesterol autoxidation are the most commonly detected oxysterols in foods (7K, 7␣OH, 7␤OH, ␣-EPOX, and ␤-EPOX). 29 Various oxysterols have been detected in extensive amounts in human tissues and fluids, including human plasma, atherogenic lipoproteins, and atherosclerotic plaque.…”

“…Lizard et al 25 and Deckert et al 27 observed that 7␤OH inhibited arterial relaxation and had the greatest ability to induce apoptosis in endothelial cells of all cholesterol oxides measured. Recently, Zieden et al 28 reported that elevated plasma 7␤OH concentration is an indication of an increased in vivo lipid peroxidation. For these reasons, we regarded 7␤OH as the most important cholesterol oxidation measure.…”

“…21,22 Some of the preferred measures of lipid peroxidation in vivo are the cholesterol oxidation products. [23][24][25][26][27][28][29] In 1994, we started a randomized-factorial, doublemasked, placebo-controlled, long-term trial to study the effect of supplementation with vitamins E and C on atherosclerotic progression and the hypothesized pathways of the expected preventive effects. Measurements of in vitro and in vivo lipid peroxidation were carried out at entry and at 12 and 36 months in a subset of 48 male participants.…”