Biomedicinal implications of high-density lipoprotein: its composition, structure, functions, and clinical applications

Cho, Kyung‐Hyun

doi:10.5483/bmbrep.2009.42.7.393

Cited by 71 publications

(39 citation statements)

References 61 publications

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“…Modification of apoA-I, such as cleavage, oxidation, nitration, and chlorination, could lead to the production of dysfunctional apoA-I and HDL (Cho, 2009a;Feng and Li, 2009). Truncation of apoA-I at the C-terminus, yielding apoA-I (1-192), results in decreased lipid-binding ability (Ji and Jonas, 1995).…”

Section: Discussionmentioning

confidence: 99%

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Modified Apolipoprotein (apo) A-I by Artificial Sweetener Causes Severe Premature Cellular Senescence and Atherosclerosis with Impairment of Functional and Structural Properties of apoA-I in Lipid-Free and Lipid-Bound State

Jang

Jeoung

Cho

2011

Molecules and Cells

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Long-term consumption of artificial sweeteners (AS) has been the recent focus of safety concerns. However, the potential risk of the AS in cardiovascular disease and lipoprotein metabolism has not been investigated sufficiently. We compared the influence of AS (aspartame, acesulfame K, and saccharin) and fructose in terms of functional and structural correlations of apolipoprotein (apo) A-I and high-density lipoproteins (HDL), which have atheroprotective effects. Long-term treatment of apoA-I with the sweetener at physiological concentration (3 mM for 168 h) resulted in loss of antioxidant and phospholipid binding activities with modification of secondary structure. The AS treated apoA-I exhibited proteolytic cleavage to produce 26 kDa-fragment. They showed pro-atherogenic properties in acetylated LDL phagocytosis of macrophages. Each sweetener alone or sweetener-treated apoA-I caused accelerated senescence in human dermal fibroblasts. These results suggest that long-term consumption of AS might accelerate atherosclerosis and senescence via impairment of function and structure of apoA-I and HDL.

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Section: Discussionmentioning

confidence: 99%

“…High-density lipoprotein (HDL) exerts many beneficial effects for the maintenance of a healthy physiologic system, including antioxidant, anti-inflammatory, and anti-thrombotic effects (Cho, 2009a;Rye and Barter, 2008). Other beneficial functions of HDL include anti-aging activities, as recently suggested by Walter (2009).…”

Section: Introductionmentioning

confidence: 99%

Modified Apolipoprotein (apo) A-I by Artificial Sweetener Causes Severe Premature Cellular Senescence and Atherosclerosis with Impairment of Functional and Structural Properties of apoA-I in Lipid-Free and Lipid-Bound State

Jang

Jeoung

Cho

2011

Molecules and Cells

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“…5). apoA-I is a major component of HDL particles, which have strong antioxidant, anti-inflammatory and anti-infective properties (23). The overexpression of apoA-I in mice elicits resistance to diet-induced atherosclerosis (24).…”

Section: Discussionmentioning

confidence: 99%

Bovine apolipoprotein (apo)A-I displays more enhanced antioxidant and anti-atherosclerotic activity in lipid-free and lipid-bound states than human and porcine apoA-I

Kim

Park

Choi

et al. 2013

International Journal of Molecular Medicine

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Abstract. Apolipoprotein A-I (apoA-I) is a major component of high-density lipoprotein (HDL), which displays anti-atherosclerotic activity in plasma. In the current study, we compared the functional and structural characteristics of human, bovine and porcine apoA-I as regards their antioxidant ability and protein stability. In the lipid-free state, the immunoreactivity of bovine and porcine apoA-I differed from that of human apoA-I and bovine and porcine apoA-I exhibited greater resistance to denaturation induced by urea treatment. Bovine apoA-I showed the weakest binding ability of dimyristoyl phosphatidylcholine; however, bovine apoA-I formed slightly larger reconstituted HDL (rHDL) particles with palmitoyl oleoyl phosphatidylcholine, with a higher number of apoA-Icontaining particles. Bovine and porcine apoA-I comprised of pentameric structures, whereas human apoA-I in the rHDL state consisted of trimeric structures. Although apoA-I from all three species showed a similar content of α-helicity in the lipidfree state (approximately 53%), bovine apoA-I showed a lower α-helicity content (approximately 66%) compared with human apoA-I (approximately 74%) in the rHDL state. Bovine apoA-I was more resistant to denaturation and glycation upon treatment with urea and fructose, respectively. Furthermore, bovine apoA-I showed a greater inhibition of cupric ion-mediated lowdensity lipoprotein (LDL) oxidation and uptake of acetylated LDL by macrophages compared with human or porcine apoA-I in the lipid-free and lipid-bound states. In conclusion, bovine apoA-I has unique functional properties in the lipid-free and lipid-bound states, and displays significantly enhanced antiatherosclerotic activity.

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“…In the healthy state, HDL exerts many beneficial effects for the maintenance of a healthy physiologic system, including antioxidant, anti-inflammatory and anti-thrombotic effects (6). LDL is the major cholesterol carrier in the plasma with heterogeneous particle size and composition.…”

Section: Introductionmentioning

confidence: 99%

Elevated HDL2-paraoxonase and reduced CETP activity are associated with a dramatically lower ratio of LDL-cholesterol/total cholesterol in a hypercholesterolemic and hypertriglyceridemic patient

Lee

Park²,

Lee³

et al. 2010

Int J Mol Med

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Abstract.A female patient (64 years of age; body mass index, 26) had a markedly and relatively low low-density lipoprotein-cholesterol (LDL-C) level (97 mg/dl) despite high serum total cholesterol (TC) (331 mg/dl) and triacylglyceride levels (307 mg/dl). Since the expected LDL-C was 222 mg/dl, there was a significant difference between the calculation and measurement based on direct enzyme assay. Only 30% of serum cholesterol was associated with LDL-C in this patient. To determine the basis for the markedly low LDL-C/TC ratio, we isolated and analyzed lipoproteins from the patient as well as age-and gender-matched controls. The patient had lowered serum CETP activity and elevated paraoxonase activity with GOT and GPT values in the normal range. The very low-density lipoprotein particles from the patient were larger than those of the controls and enriched with lipid and protein, while the LDL from the patient (LDL-P) had a lower particle number and protein content than the controls. The LDL-P was more resistant to cupric ion-mediated oxidation. HDL 2 from the patient (HDL 2 -P) had highly enhanced paraoxonase activity and antioxidant ability. The patient had a 1.5-fold higher level of apolipoprotein (apo) A-I expression in HDL 2 . ApoA-I in HDL 2 and HDL 3 from the patient showed no fragmentation, while the control had fragmented bands (17 and 21 kDa) in the HDL. The HDL 2 -P also had a larger particle size and greater protein content with less lipid content. HDL 3 -associated cholesteryl ester transfer protein was reduced in the patient, although the particle size was similar to the controls. In conclusion, a patient who had a markedly lower LDL-C/TC ratio despite hyperlipidemia associated with higher paraoxonase activity, higher apoA-I level and lower CETP activity without fragmentation of apoA-I in the HDL fraction is presented. The enhanced antioxidant and anti-inflammatory activity of HDL might contribute to the low LDL-C/TC ratio in this patient. IntroductionDyslipidemia is an important risk factor for coronary heart disease (CHD), and low-density lipoprotein-cholesterol (LDL-C) is a strong biomarker to predict the risk of CHD (1). Patients with diabetes and metabolic syndrome have a strong association with atherogenic dyslipidemia, which includes high levels of triacylglycerides (TG) and elevated levels of small dense LDL (2). The most widely used method to calculate LDL-C is the Friedewald equation (3), although several methods of direct measurement are currently used. However, the estimated LDL-C using the Friedewald equation does not produce an accurate number when the plasma TG is >400 mg/dl or when plasma is not collected in the fasting state (4). Otherwise, a discrepancy in the number of measured LDL-C and the Friedewald LDL-C might indicate a modified lipoprotein metabolism. The National Cholesterol Education Program (NCEP) guidelines recommend development of direct assays to measure LDL-C (5) since LDL-C can be influenced by the dynamic interaction of apolipoprotein and several lipoprotein-associat...

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Biomedicinal implications of high-density lipoprotein: its composition, structure, functions, and clinical applications

Abstract: High-density lipoprotein (HDL) is

Cited by 71 publications

References 61 publications

Modified Apolipoprotein (apo) A-I by Artificial Sweetener Causes Severe Premature Cellular Senescence and Atherosclerosis with Impairment of Functional and Structural Properties of apoA-I in Lipid-Free and Lipid-Bound State

Modified Apolipoprotein (apo) A-I by Artificial Sweetener Causes Severe Premature Cellular Senescence and Atherosclerosis with Impairment of Functional and Structural Properties of apoA-I in Lipid-Free and Lipid-Bound State

Bovine apolipoprotein (apo)A-I displays more enhanced antioxidant and anti-atherosclerotic activity in lipid-free and lipid-bound states than human and porcine apoA-I

Elevated HDL2-paraoxonase and reduced CETP activity are associated with a dramatically lower ratio of LDL-cholesterol/total cholesterol in a hypercholesterolemic and hypertriglyceridemic patient

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