Background and aims: Epidemiological data showing that high-density lipoprotein cholesterol (HDL-C)is inversely associated with cardiovascular disease have led to the idea that cholesterol contained in this lipoprotein may be protective. Against, recent evidence suggests that the athero-protection from HDLs may result from other functions, unrelated to the carried cholesterol. HDL accessory proteins, such as paraoxonase 1 (PON1), have been suggested to endows HDL with antioxidant and anti-inflammatory properties and to contribute to the athero-protective function of the lipoprotein. We aimed to evaluate whether extreme fluctuation in HDL-C levels correlates with PON1 activity. Methods: Levels of PON1-related arylesterase and lactonase were assessed in subjects with primary hyperalphalipoproteinemia (HAL, HDL-C>90th percentile), hypoalphalipoproteinemia (HA, HDL-C<10th percentile)and controls. Cholesterol efflux capacity (CEC)through several pathways and other metabolic parameters and markers of vascular disease were also determined. Results: Despite the marked change in HDL-C and Apoliprotein A1 (APO A1)(p < 0.001 for all comparisons), arylesterase and lactonase were only slightly increased in HAL compared with HA subjects (p < 0.05), but not vs. controls. This change in PON1 activities was no longer significant after adjustment for either HDL-C or APO A1. Both enzymatic activities were positively associated only with aqueous diffusion CEC (r = 0.318, p < 0.05 and r = 0.355, p < 0.05, respectively)and negatively with the presence of plaques (p < 0.05). Conclusions: We showed that extreme high/low HDL-C levels are not associated with equal increase/decrease in PON1 activities. This enzyme appears to contribute to the HDL role in reverse cholesterol transport and anti-atherosclerosis processes. Further investigation is required to corroborate our findings.

Paraoxonase-1 activities in individuals with different HDL circulating levels: Implication in reverse cholesterol transport and early vascular damage

Cervellati C.
Primo
;
Vigna G. B.
Secondo
;
Trentini A.;Sanz J. M.;Dalla Nora E.;Morieri M. L.;Zuliani G.
Penultimo
;
Passaro A.
Ultimo
2019

Abstract

Background and aims: Epidemiological data showing that high-density lipoprotein cholesterol (HDL-C)is inversely associated with cardiovascular disease have led to the idea that cholesterol contained in this lipoprotein may be protective. Against, recent evidence suggests that the athero-protection from HDLs may result from other functions, unrelated to the carried cholesterol. HDL accessory proteins, such as paraoxonase 1 (PON1), have been suggested to endows HDL with antioxidant and anti-inflammatory properties and to contribute to the athero-protective function of the lipoprotein. We aimed to evaluate whether extreme fluctuation in HDL-C levels correlates with PON1 activity. Methods: Levels of PON1-related arylesterase and lactonase were assessed in subjects with primary hyperalphalipoproteinemia (HAL, HDL-C>90th percentile), hypoalphalipoproteinemia (HA, HDL-C<10th percentile)and controls. Cholesterol efflux capacity (CEC)through several pathways and other metabolic parameters and markers of vascular disease were also determined. Results: Despite the marked change in HDL-C and Apoliprotein A1 (APO A1)(p < 0.001 for all comparisons), arylesterase and lactonase were only slightly increased in HAL compared with HA subjects (p < 0.05), but not vs. controls. This change in PON1 activities was no longer significant after adjustment for either HDL-C or APO A1. Both enzymatic activities were positively associated only with aqueous diffusion CEC (r = 0.318, p < 0.05 and r = 0.355, p < 0.05, respectively)and negatively with the presence of plaques (p < 0.05). Conclusions: We showed that extreme high/low HDL-C levels are not associated with equal increase/decrease in PON1 activities. This enzyme appears to contribute to the HDL role in reverse cholesterol transport and anti-atherosclerosis processes. Further investigation is required to corroborate our findings.
2019
Cervellati, C.; Vigna, G. B.; Trentini, A.; Sanz, J. M.; Zimetti, F.; Dalla Nora, E.; Morieri, M. L.; Zuliani, G.; Passaro, A.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2405386
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