Oxidative stress-mediated inflammation is crucial in atherosclerosis. Lipoprotein phospholipase A2 (Lp-PLA2) is produced by macrophages and foam cells in atherosclerotic plaques and hydrolyzes the sn-2 fatty acids of oxidized phospholipids to yield oxidized fatty acids and lysophosphatidylcholine (LysoPC). Nuclear erythroid-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is involved in inducing genes coding for antioxidants, including heme oxygenase-1 (HO-1). Coronary artery calcium score (CAC) is a non-invasive method to evaluate coronary atherosclerotic burden. CAC and Lp-PLA2 add significantly to risk prediction, particularly among subjects at intermediate risk (IR). In IR subjects compared to high-risk (HR) we evaluate 1) the expression of the proinflammatory molecule Lp-PLA2 and of the protective antioxidant Nrf2/ARE pathway in peripheral blood mononuclear cells (PBMC), 2) levels of systemic indices of oxidative stress and inflammation, 3) the CAC score. 90 age-and sex-matched subjects participated in the study: 30 controls (C), 30 IR and 30 HR subjects; SCORE risk charts were used to identify IR and HR. In PBMC was evaluated mRNA expression of Lp-PLA2, Nrf2 and HO-1 (Real time PCR), LysoPC (HPLC/mass spectrometry), hsCRP (turbidimetric method), CAC (multislice computed tomography and expressed as Agatson score, AS). No significant differences existed among the groups with respect to body mass index, blood pressure, heart rate, lipid and glucose profile. HR PBMC showed significantly reduced mRNA expression of Nrf2 and HO-1 than IR and C (P < 0.01). On the contrary HR subjects had an increased mRNA expression of Lp-PLA2 compared to C and IR subjects (P < 0.01). Plasma levels of hsCRP and LysoPC were higher in HR than in IR and C subjects (P < 0.05). AS was significantly higher in HR than in IR (P < 0.01). In all subjects we found a significant positive correlation between Agatston score and LysoPC. The protective Nrf2/ARE pathway is not appropriately expressed and Lp-PLA2 is overexpressed in IR PBMC favouring inflammation. The relation between LysoPC and AS suggests that LysPC is an useful marker of subclinical atherosclerosis.

ALTERED EXPRESSION OF INFLAMMATORY/OXIDATIVE GENES IN PBMC AND EMERGING CARDIOVASCULAR MARKERS (LYSO PC AND CALCIUM SCORE) IN CARDIOVASCULAR RISK SUBJECTS: PP.2.60

FRATTA PASINI, Anna Maria;MALAGO', Roberto;GARBIN, Ulisse;STRANIERI, Chiara;MANFRO, Stefania;MOZZINI, Chiara;VALLERIO, Paola;COMINACINI, Luciano
2010

Abstract

Oxidative stress-mediated inflammation is crucial in atherosclerosis. Lipoprotein phospholipase A2 (Lp-PLA2) is produced by macrophages and foam cells in atherosclerotic plaques and hydrolyzes the sn-2 fatty acids of oxidized phospholipids to yield oxidized fatty acids and lysophosphatidylcholine (LysoPC). Nuclear erythroid-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is involved in inducing genes coding for antioxidants, including heme oxygenase-1 (HO-1). Coronary artery calcium score (CAC) is a non-invasive method to evaluate coronary atherosclerotic burden. CAC and Lp-PLA2 add significantly to risk prediction, particularly among subjects at intermediate risk (IR). In IR subjects compared to high-risk (HR) we evaluate 1) the expression of the proinflammatory molecule Lp-PLA2 and of the protective antioxidant Nrf2/ARE pathway in peripheral blood mononuclear cells (PBMC), 2) levels of systemic indices of oxidative stress and inflammation, 3) the CAC score. 90 age-and sex-matched subjects participated in the study: 30 controls (C), 30 IR and 30 HR subjects; SCORE risk charts were used to identify IR and HR. In PBMC was evaluated mRNA expression of Lp-PLA2, Nrf2 and HO-1 (Real time PCR), LysoPC (HPLC/mass spectrometry), hsCRP (turbidimetric method), CAC (multislice computed tomography and expressed as Agatson score, AS). No significant differences existed among the groups with respect to body mass index, blood pressure, heart rate, lipid and glucose profile. HR PBMC showed significantly reduced mRNA expression of Nrf2 and HO-1 than IR and C (P < 0.01). On the contrary HR subjects had an increased mRNA expression of Lp-PLA2 compared to C and IR subjects (P < 0.01). Plasma levels of hsCRP and LysoPC were higher in HR than in IR and C subjects (P < 0.05). AS was significantly higher in HR than in IR (P < 0.01). In all subjects we found a significant positive correlation between Agatston score and LysoPC. The protective Nrf2/ARE pathway is not appropriately expressed and Lp-PLA2 is overexpressed in IR PBMC favouring inflammation. The relation between LysoPC and AS suggests that LysPC is an useful marker of subclinical atherosclerosis.
cardiovascular risk subjects, PBMC gene expression
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/949083
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact