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Increased Levels of Human Carotid Lesion Linoleic Acid Hydroperoxide in Symptomatic and Asymptomatic Patients Is Inversely Correlated with Serum HDL and Paraoxonase 1 Activity.

Cohen E, Aviram M, Khatib S, Rabin A, Mannheim D, Karmeli R, Vaya J - J Lipids (2012)

Bottom Line: The PON1-specific inhibitor 2-hydroxyquinoline almost completely inhibited paraoxonase and lactonase activities, while only moderately inhibiting arylesterase activity.Oxysterol and triglyceride levels in plaques from symptomatic and asymptomatic patients did not differ significantly, but plaques from symptomatic patients had significantly higher (135%) linoleic acid hydroperoxide (LA-13OOH) levels.Their serum PON1 activity, cholesterol and triglyceride levels did not differ significantly, but symptomatic patients had significantly lower (28%) serum HDL levels and higher (18%) HbA1c levels.

View Article: PubMed Central - PubMed

Affiliation: Oxidative Stress Research Laboratory, Migal-Galilee Technology Center and Tel Hai College, P.O. Box 831, Kiryat Shmona 11016, Israel.

ABSTRACT
Human carotid plaque components interact directly with circulating blood elements and thus they might affect each other. We determined plaque paraoxonase1 (PON1) hydrolytic-catalytic activity and compared plaque and blood levels of lipids, HDL, PON1, and HbA1c, as well as plaque-oxidized lipids in symptomatic and asymptomatic patients. Human carotid plaques were obtained from symptomatic and asymptomatic patients undergoing routine endarterectomy, and the lesions were ground and extracted for PON activity and lipid content determinations. Plaque PONs preserved paraoxonase, arylesterase, and lactonase activities. The PON1-specific inhibitor 2-hydroxyquinoline almost completely inhibited paraoxonase and lactonase activities, while only moderately inhibiting arylesterase activity. Oxysterol and triglyceride levels in plaques from symptomatic and asymptomatic patients did not differ significantly, but plaques from symptomatic patients had significantly higher (135%) linoleic acid hydroperoxide (LA-13OOH) levels. Their serum PON1 activity, cholesterol and triglyceride levels did not differ significantly, but symptomatic patients had significantly lower (28%) serum HDL levels and higher (18%) HbA1c levels. Thus LA-13OOH, a major atherogenic plaque element, showed significant negative correlations with serum PON1 activity and HDL levels, and a positive correlation with the prodiabetic atherogenic HbA1c. Plaque PON1 retains its activity and may decrease plaque atherogenicity by reducing specific oxidized lipids (e.g., LA-13OOH). The inverse correlation between plaque LA-13OOH level and serum HDL level and PON1 activity suggests a role for serum HDL and PON1 in LA-13OOH accumulation.

No MeSH data available.


Related in: MedlinePlus

Hydrolytic activities of paraoxonases (PONs) in human carotid plaque homogenate and of recombinant PON1 (rePON1). (a): Homogenate paraoxonase (paraoxon), (b): lactonase (TBBL), and (c): arylesterase (4-nitrophenyl acetate) activities; (d): rePON1 paraoxonase, (e): lactonase, and (f): arylesterase activities, with or without 2-hydroxyquinoline (2HQ).
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fig1: Hydrolytic activities of paraoxonases (PONs) in human carotid plaque homogenate and of recombinant PON1 (rePON1). (a): Homogenate paraoxonase (paraoxon), (b): lactonase (TBBL), and (c): arylesterase (4-nitrophenyl acetate) activities; (d): rePON1 paraoxonase, (e): lactonase, and (f): arylesterase activities, with or without 2-hydroxyquinoline (2HQ).

Mentions: Immunohistochemical analysis has recently revealed the presence of PON1, PON3 [16], and PON2 [23] in carotid lesions. However, such analyses do not indicate whether the enzymes in the plaque still possess hydrolytic activity. As part of our ongoing research into the chemical composition of the human carotid plaque, the mechanism by which plaque components interrelate, and their possible dual effects with blood components, we tested whether plaque PONs are still active. Human carotid lesions were ground to a powder under liquid nitrogen. The powder was extracted with Tris buffer and then centrifuged (see Section 2). The supernatant was used for determination of PON paraoxonase, lactonase and arylesterase activities, with or without the addition of the PON1 inhibitor 2HQ. All three PON activities were preserved in the plaque homogenate, and 2HQ almost completely inhibited paraoxonase and lactonase activities (from 2.9 to 0.014 and from 0.115 to 0.008 U/mg protein, resp., Figures 1(a) and 1(b)), whereas it only slightly decreased arylesterase activity (from 3.3 to 2.5 U/mg protein) (Figure 1(c)). The effects of 2HQ on PON's hydrolytic properties were reexamined with rePON1. 2HQ inhibited rePON1 paraoxonase, lactonase, and arylesterase activities almost completely (from  9006 ± 161  to 1819 ± 30,  365 ± 6  to 65.6 ± 0.7, and  118 ± 14  to 9.9 ± 2.8 U/mg rePON1 protein, resp.) (Figures 1(d)–1(f)). These results indicated that PONs that are present in the plaques preserve all three of their hydrolytic activities.


Increased Levels of Human Carotid Lesion Linoleic Acid Hydroperoxide in Symptomatic and Asymptomatic Patients Is Inversely Correlated with Serum HDL and Paraoxonase 1 Activity.

Cohen E, Aviram M, Khatib S, Rabin A, Mannheim D, Karmeli R, Vaya J - J Lipids (2012)

Hydrolytic activities of paraoxonases (PONs) in human carotid plaque homogenate and of recombinant PON1 (rePON1). (a): Homogenate paraoxonase (paraoxon), (b): lactonase (TBBL), and (c): arylesterase (4-nitrophenyl acetate) activities; (d): rePON1 paraoxonase, (e): lactonase, and (f): arylesterase activities, with or without 2-hydroxyquinoline (2HQ).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3368548&req=5

fig1: Hydrolytic activities of paraoxonases (PONs) in human carotid plaque homogenate and of recombinant PON1 (rePON1). (a): Homogenate paraoxonase (paraoxon), (b): lactonase (TBBL), and (c): arylesterase (4-nitrophenyl acetate) activities; (d): rePON1 paraoxonase, (e): lactonase, and (f): arylesterase activities, with or without 2-hydroxyquinoline (2HQ).
Mentions: Immunohistochemical analysis has recently revealed the presence of PON1, PON3 [16], and PON2 [23] in carotid lesions. However, such analyses do not indicate whether the enzymes in the plaque still possess hydrolytic activity. As part of our ongoing research into the chemical composition of the human carotid plaque, the mechanism by which plaque components interrelate, and their possible dual effects with blood components, we tested whether plaque PONs are still active. Human carotid lesions were ground to a powder under liquid nitrogen. The powder was extracted with Tris buffer and then centrifuged (see Section 2). The supernatant was used for determination of PON paraoxonase, lactonase and arylesterase activities, with or without the addition of the PON1 inhibitor 2HQ. All three PON activities were preserved in the plaque homogenate, and 2HQ almost completely inhibited paraoxonase and lactonase activities (from 2.9 to 0.014 and from 0.115 to 0.008 U/mg protein, resp., Figures 1(a) and 1(b)), whereas it only slightly decreased arylesterase activity (from 3.3 to 2.5 U/mg protein) (Figure 1(c)). The effects of 2HQ on PON's hydrolytic properties were reexamined with rePON1. 2HQ inhibited rePON1 paraoxonase, lactonase, and arylesterase activities almost completely (from  9006 ± 161  to 1819 ± 30,  365 ± 6  to 65.6 ± 0.7, and  118 ± 14  to 9.9 ± 2.8 U/mg rePON1 protein, resp.) (Figures 1(d)–1(f)). These results indicated that PONs that are present in the plaques preserve all three of their hydrolytic activities.

Bottom Line: The PON1-specific inhibitor 2-hydroxyquinoline almost completely inhibited paraoxonase and lactonase activities, while only moderately inhibiting arylesterase activity.Oxysterol and triglyceride levels in plaques from symptomatic and asymptomatic patients did not differ significantly, but plaques from symptomatic patients had significantly higher (135%) linoleic acid hydroperoxide (LA-13OOH) levels.Their serum PON1 activity, cholesterol and triglyceride levels did not differ significantly, but symptomatic patients had significantly lower (28%) serum HDL levels and higher (18%) HbA1c levels.

View Article: PubMed Central - PubMed

Affiliation: Oxidative Stress Research Laboratory, Migal-Galilee Technology Center and Tel Hai College, P.O. Box 831, Kiryat Shmona 11016, Israel.

ABSTRACT
Human carotid plaque components interact directly with circulating blood elements and thus they might affect each other. We determined plaque paraoxonase1 (PON1) hydrolytic-catalytic activity and compared plaque and blood levels of lipids, HDL, PON1, and HbA1c, as well as plaque-oxidized lipids in symptomatic and asymptomatic patients. Human carotid plaques were obtained from symptomatic and asymptomatic patients undergoing routine endarterectomy, and the lesions were ground and extracted for PON activity and lipid content determinations. Plaque PONs preserved paraoxonase, arylesterase, and lactonase activities. The PON1-specific inhibitor 2-hydroxyquinoline almost completely inhibited paraoxonase and lactonase activities, while only moderately inhibiting arylesterase activity. Oxysterol and triglyceride levels in plaques from symptomatic and asymptomatic patients did not differ significantly, but plaques from symptomatic patients had significantly higher (135%) linoleic acid hydroperoxide (LA-13OOH) levels. Their serum PON1 activity, cholesterol and triglyceride levels did not differ significantly, but symptomatic patients had significantly lower (28%) serum HDL levels and higher (18%) HbA1c levels. Thus LA-13OOH, a major atherogenic plaque element, showed significant negative correlations with serum PON1 activity and HDL levels, and a positive correlation with the prodiabetic atherogenic HbA1c. Plaque PON1 retains its activity and may decrease plaque atherogenicity by reducing specific oxidized lipids (e.g., LA-13OOH). The inverse correlation between plaque LA-13OOH level and serum HDL level and PON1 activity suggests a role for serum HDL and PON1 in LA-13OOH accumulation.

No MeSH data available.


Related in: MedlinePlus