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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

Human plaque linoleic acid hydroperoxide (LA-13OOH) level versus serum HDL, serum PON1 activity and blood hemoglobin (Hb) A1c. Human plaque LA-13OOH is inversely correlated with (a): serum PON1 lactonase activity and (b): serum HDL, but (c): positively correlated with blood HbA1c.
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fig2: Human plaque linoleic acid hydroperoxide (LA-13OOH) level versus serum HDL, serum PON1 activity and blood hemoglobin (Hb) A1c. Human plaque LA-13OOH is inversely correlated with (a): serum PON1 lactonase activity and (b): serum HDL, but (c): positively correlated with blood HbA1c.

Mentions: Previous studies from our group have shown that LA-13OOH (with the hydroperoxide at position 13 of linoleic acid) inhibits PON1 by specific interaction with the enzyme's Cys284. Thus, LA-13OOH is considered an atherogenic factor in the plaque which can augment oxidative stress and progression of atherosclerosis [22]. This led us to correlate LA-13OOH level in the plaque with other atherogenic and antiatherogenic elements in the blood of the same patient, to assess the possible correlation between plaque status and a specific component in the blood. Results showed that plaque LA-13OOH level is indeed inversely correlated with two antiatherogenic elements in the blood: serum PON1 lactonase activity (R2 = 0.35, P = 0.01, Figure 2(a)) and HDL cholesterol (R2 = 0.3, P = 0.027, Figure 2(b)). In addition, a direct correlation was found between the two atherogenic elements, LA-13OOH and HbA1c (R2 = 0.27, P = 0.038, Figure 2(c)).


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)

Human plaque linoleic acid hydroperoxide (LA-13OOH) level versus serum HDL, serum PON1 activity and blood hemoglobin (Hb) A1c. Human plaque LA-13OOH is inversely correlated with (a): serum PON1 lactonase activity and (b): serum HDL, but (c): positively correlated with blood HbA1c.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: Human plaque linoleic acid hydroperoxide (LA-13OOH) level versus serum HDL, serum PON1 activity and blood hemoglobin (Hb) A1c. Human plaque LA-13OOH is inversely correlated with (a): serum PON1 lactonase activity and (b): serum HDL, but (c): positively correlated with blood HbA1c.
Mentions: Previous studies from our group have shown that LA-13OOH (with the hydroperoxide at position 13 of linoleic acid) inhibits PON1 by specific interaction with the enzyme's Cys284. Thus, LA-13OOH is considered an atherogenic factor in the plaque which can augment oxidative stress and progression of atherosclerosis [22]. This led us to correlate LA-13OOH level in the plaque with other atherogenic and antiatherogenic elements in the blood of the same patient, to assess the possible correlation between plaque status and a specific component in the blood. Results showed that plaque LA-13OOH level is indeed inversely correlated with two antiatherogenic elements in the blood: serum PON1 lactonase activity (R2 = 0.35, P = 0.01, Figure 2(a)) and HDL cholesterol (R2 = 0.3, P = 0.027, Figure 2(b)). In addition, a direct correlation was found between the two atherogenic elements, LA-13OOH and HbA1c (R2 = 0.27, P = 0.038, Figure 2(c)).

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