The associations of oxidized high-density lipoprotein lipids with risk factors for atherosclerosis: The Cardiovascular Risk in Young Finns Study

Kresanov, Petri; Ahotupa, Markku; Vasankari, Tommi; Kaikkonen, Jari; Kähönen, Mika; Lehtimäki, Terho; Viikari, Jorma; Raitakari, Olli T.

doi:10.1016/j.freeradbiomed.2013.09.023

Cited by 28 publications

(40 citation statements)

References 27 publications

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“…It has been reported that oxHDL has reduced capacity to perform reverse lipid transport and is associated with elevated risk for atherosclerosis in adults (Huang et al, 2014;Nicholls et al, 2005;Schindhelm et al, 2009;Shao et al, 2006Shao et al, , 2010. Consistent with the current findings, in a recent report from the Young Finns Study it was shown that the content of oxidized lipids in HDL and LDL particles were positively correlated (Kresanov et al, 2013). Those findings may reflect the HDL capacity to remove lipid peroxides from circulation and tissues through reverse cholesterol transport.…”

Section: Discussionsupporting

confidence: 91%

Oxidized HDL and LDL in adolescents with type 2 diabetes compared to normal weight and obese peers

Marin

Dasari

Tryggestad

et al. 2015

Journal of Diabetes and its Complications

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Section: Discussionsupporting

confidence: 91%

Oxidized HDL and LDL in adolescents with type 2 diabetes compared to normal weight and obese peers

Marin

Dasari

Tryggestad

et al. 2015

Journal of Diabetes and its Complications

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“…Many factors influence the ability of HDL to efflux cellular cholesterol to acceptor apoproteins, including modification of the acceptor proteins under conditions of oxidative stress ( Kresanov et al, 2013 ) and inflammation ( Morgantini et al, 2011 ). Additionally, players in the cells that promote lipid efflux get influenced under certain pathophysiological states, including diabetes ( Klein, 1995 ) and inflammation ( Morgantini et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

Lack of Correlation of Plasma HDL With Fecal Cholesterol and Plasma Cholesterol Efflux Capacity Suggests Importance of HDL Functionality in Attenuation of Atherosclerosis

et al. 2018

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A number of clinical findings suggested HDL-raising as a plausible approach to treat residual risk of CVD. However, lack of CVD risk reduction by elevated HDL cholesterol (HDL-C) through cholesterol ester transfer protein (CETP) inhibition and enhanced risk reduction in apolipoprotein A-I Milano (apoAI-M) individuals with low HDL-C shifted the focus from HDL-C level to HDL function. In the present study, we investigated correlations between HDL-C, HDL function, fecal cholesterol excretion, and ex vivo plasma cholesterol efflux capacity (CEC) in animal models using two HDL modulators, LXR and PPAR-α agonists. In C57Bl mice, LXR agonist, T1317, raised HDL-C by 30%, while PPAR-α agonist, fenofibrate, reduced HDL-C by 30%, but fecal cholesterol showed twofold increase in both cases. CEC showed a 30–40% increase. Combination of LXR and PPAR-α agonists showed no changes in HDL-C, but, interestingly, fecal cholesterol increased by 4.5-fold, and CEC by 40%, suggesting existence of additional pathway for fecal cholesterol excretion. Regression analysis showed a lack of correlation between HDL-C and fecal cholesterol and CEC, while fecal cholesterol showed significant correlation with CEC, a measure of HDL function. ABCA1 and G1, the two important players in RCT showed greater induction with LXR agonist than PPAR-α agonist. HDL-C increased by 40 and 80% in LXR and PPAR-α treated apoA-I transgenic mice, respectively, with 80% increase in fecal cholesterol. A fivefold increase in fecal cholesterol with no correlation with either plasma HDL-C or CEC following co-treatment with LXR and PPAR-α agonists suggested existence of an HDL-independent pathway for body cholesterol elimination. In hyperlipidemic diabetic ob/ob mice also combination of LXR and PPAR-α agonists showed marked increases in fecal cholesterol content (10–20-fold), while HDL-C rise was only 40%, further suggesting HDL-independent elimination of body cholesterol in mice treated with combination of LXR and PPAR-α agonists. Atherosclerosis attenuation by LXR and PPAR-α agonists in LDLr-deficient mice was associated with increased fecal cholesterol, but not HDL-C. However, fecal cholesterol counts showed inverse correlation with aortic cholesteryl ester content. These data suggest: (a) lack of correlation between HDL-C and fecal or aortic cholesterol content; (b) HDL function (CEC) correlated with fecal cholesterol content; (c) association of reduced aortic lipids in LDLr−/− mice with increased fecal cholesterol, but not with HDL-C, and (d) existence of an HDL-independent pathway for fecal cholesterol excretion following co-treatment with LXR and PPAR-α agonists.

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“…One potential mechanism may be the lipid peroxide reverse transporting capacity of HDL [17]. In line with this, we recently demonstrated at the population level that an elevated cardiovascular risk profile is associated with lower levels of oxidized HDL lipids (oxHDLlipids) [18]. At present, PON-1 is proposed to be a factor in the anti-oxidant activity of HDL based on studies performed in vitro [13].…”

Section: Introductionmentioning

confidence: 71%

Paraoxonase-1 and oxidized lipoprotein lipids. The Cardiovascular Risk in Young Finns Study

et al. 2015

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The associations of oxidized high-density lipoprotein lipids with risk factors for atherosclerosis: The Cardiovascular Risk in Young Finns Study

Cited by 28 publications

References 27 publications

Oxidized HDL and LDL in adolescents with type 2 diabetes compared to normal weight and obese peers

Oxidized HDL and LDL in adolescents with type 2 diabetes compared to normal weight and obese peers

Lack of Correlation of Plasma HDL With Fecal Cholesterol and Plasma Cholesterol Efflux Capacity Suggests Importance of HDL Functionality in Attenuation of Atherosclerosis

Paraoxonase-1 and oxidized lipoprotein lipids. The Cardiovascular Risk in Young Finns Study

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