A general method for the isolation of haptoglobin 1-1, 2-1, and 2-2 from human plasma

Rademacher, Bruce E.; Steele, William J.

doi:10.1016/0003-2697(87)90621-x

Cited by 27 publications

(16 citation statements)

References 17 publications

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“…It is possible that under oxidative stress conditions, Hb⅐Hp⅐Hx complexes are formed and associate with HDL for rapid clearance from the circulation. Indeed Hp has been reported to associate with apoA-I, the major protein component of HDL (41)(42)(43)(44). Hp association of apoA-I alters HDL function (45,46).…”

Section: Discussionmentioning

confidence: 99%

Differential Association of Hemoglobin with Proinflammatory High Density Lipoproteins in Atherogenic/Hyperlipidemic Mice

Watanabe

Chou

Liao

et al. 2007

Journal of Biological Chemistry

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Studies in both mice and humans suggest that the anti-or proinflammatory nature of high density lipoprotein (HDL) may be a more sensitive predictor of risk for coronary heart disease events. In this study, we report the identification and characterization of two proteins (m/z 14,900 and 15,600) that are most dramatically associated with HDL in mouse models of atherosclerosis. Mass spectral analyses of proinflammatory HDL identified the two peaks to be hemoglobin (Hb) ␣ and ␤ chains, respectively, with no apparent post-translational modification. Biochemical analysis confirmed the differential association of Hb with HDL from hyperlipidemic mice. We further show that HDL-associated Hb is predominantly in the oxyHb form with distinct physical and chemical properties. Furthermore oxyHbcontaining proinflammatory HDL potently consumed nitric oxide and contracted arterial vessels ex vivo. Moreover Hb also was found differentially associated with HDL from coronary heart disease patients compared with healthy controls. Our data suggest that Hb contributes to the proinflammatory nature of HDL in mouse and human models of atherosclerosis and may serve as a novel biomarker for atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

Differential Association of Hemoglobin with Proinflammatory High Density Lipoproteins in Atherogenic/Hyperlipidemic Mice

Watanabe

Chou

Liao

et al. 2007

Journal of Biological Chemistry

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“…In this paper, we have shown that Hb, Hp, and Hx are associated with HDL in both CHD patients and mouse models of hyperlipidemia/atherosclerosis. Hp has been reported to associate with apoA-1, the major protein component of HDL (37)(38)(39)(40), and alter HDL function by impairing lecithin-cholesterol acyltransferase activation (41).…”

Section: Discussionmentioning

confidence: 99%

Hemoglobin and Its Scavenger Protein Haptoglobin Associate with ApoA-1-containing Particles and Influence the Inflammatory Properties and Function of High Density Lipoprotein

Watanabe

Grijalva

Hama

et al. 2009

Journal of Biological Chemistry

107

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Hemoglobin (Hb) uniquely associates with proinflammatory HDL in atherogenic mice and coronary heart disease (CHD) patients. In this paper, we report that Hb and its scavenger proteins, haptoglobin (Hp) and hemopexin (Hx) are significantly increased in apoA-1-containing particles of HDL both in mouse models of hyperlipidemia and in CHD patients, when compared with wild type mice and healthy donors, respectively. We further demonstrate that the association of Hb, Hp, and Hx proteins with HDL positively correlates with inflammatory properties of HDL and systemic inflammation in CHD patients. Interestingly, HDL from Hp Atherosclerosis is the leading cause of morbidity and mortality in Western society. The inverse relationship between HDL 2 cholesterol and the risk of atherosclerosis is well established. Although HDL cholesterol is an epidemiological predictor of risk for coronary heart disease (CHD) (1), a significant number of CHD events occur in patients with normal LDL and HDL cholesterol levels (1, 2). Based on a number of recent studies in both animal models and human samples, it appears that the anti-or proinflammatory nature of HDL may be a more sensitive indicator of the presence or absence of atherosclerosis than HDL cholesterol levels. HDL exerts anti-inflammatory functions by promoting reverse cholesterol transport and preventing the oxidation of LDL (3, 4). We have previously shown that the anti-inflammatory functions of HDL can be impaired in humans (5) rabbits (6), and mice (7) during inflammatory processes. This impaired HDL is proinflammatory in nature, as characterized by (i) decreased levels and activity of anti-inflammatory, antioxidant factors, including apolipoprotein A1 (apoA-1) and PON1 (paraoxonase 1) (8); (ii) gain of proinflammatory proteins, such as serum amyloid A and ceruloplasmin (6); (iii) increased lipid hydroperoxide (LOOH) content (9); (iv) reduced potential to efflux cholesterol (10); and (v) diminished ability to prevent LDL oxidation (11). The molecular changes and mechanisms that promote anti-inflammatory HDL conversion to proinflammatory HDL are currently not well understood.We recently reported the identification and characterization of Hb associated with proinflammatory HDL in atherogenic/ hyperlipidemic mice and in human CHD patients (12). We demonstrated that under normal circumstances, a small amount of Hb is always found outside of red blood cells (RBC) in the non-lipoprotein fractions of serum (on the order of 10 M compared with the Ͼ1 M concentration of Hb in RBC). We further demonstrated that under conditions of hyperlipidemia in mice and in CHD patients, the non-RBC Hb moves out of the non-lipoprotein fractions and associates with HDL. This HDLassociated Hb was shown to play an important role in the modulation of HDL function, suggesting that Hb is not only a novel biomarker but may also serve as a therapeutic target for atherosclerosis (12). We therefore sought to determine the molecular mechanisms that play a role in the association of Hb with HDL.Hp and Hx are plas...

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“…Decreased LCAT activity might also depend on reduced stimulation by ApoA-I. This phenomenon might result from ApoA-I oxidation (McCall et al, 1995;Bielicki et al, 1996) or binding to Haptoglobin [Hpt] (Rademacher and Steele, 1987;Kunitake et al, 1994;Porta et al, 1999), a plasma glycoprotein exhibiting enhanced levels during the acute phase of the inflammation (Sadrzadeh and Bozorgmehr, 2004). In fact, the ratio of Hpt with ApoA-I was found negatively correlated with the LCAT activity both in vitro and in ovarian follicular fluid, thus suggesting that Hpt inhibits the enzyme by preventing the ApoA-I-dependent stimulation of the catalytic activity .…”

Section: Introductionmentioning

confidence: 98%

Apolipoprotein A-I-dependent cholesterol esterification in patients with rheumatoid arthritis

Cigliano

Spagnuolo

Cuomo³

et al. 2005

Life Sciences

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A general method for the isolation of haptoglobin 1-1, 2-1, and 2-2 from human plasma

Cited by 27 publications

References 17 publications

Differential Association of Hemoglobin with Proinflammatory High Density Lipoproteins in Atherogenic/Hyperlipidemic Mice

Differential Association of Hemoglobin with Proinflammatory High Density Lipoproteins in Atherogenic/Hyperlipidemic Mice

Hemoglobin and Its Scavenger Protein Haptoglobin Associate with ApoA-1-containing Particles and Influence the Inflammatory Properties and Function of High Density Lipoprotein

Apolipoprotein A-I-dependent cholesterol esterification in patients with rheumatoid arthritis

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