Arterial Tissue And Plasma Concentration Of Enzymatic-driven Oxysterols Are Associated With Severe Peripheral Atherosclerotic Disease And Systemic Infl Ammatory Activity

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Introduction. Cholesterol undergoes oxidation via both enzymatic stress-and free radical-mediated mechanisms, generating a wide range of oxysterols. In contrast to oxidative stress-driven metabolites, enzymatic stress-derived oxysterols are scarcely studied in their association with atherosclerotic disease in humans. Methods. 24S-hydroxycholesterol (24S-HC), 25-hydroxycholesterol (25-HC), and 27-hydroxycholesterol (27-HC) were assessed in plasma and arteries with atherosclerotic plaques from 10 patients (54 -84 years) with severe peripheral artery disease (PAD) as well as arteries free of atherosclerotic plaques from 13 individuals (45 - 78 years, controls). Results. Plasma 25-HC was higher in PAD individuals than in controls (6.3[2] vs. 3.9[1.9] ng/mgCol; p = 0.004). 24S-HC and 27-HC levels were, respectively, five-and 20-fold higher in the arterial tissue of PAD individuals than in those of the controls (p = 0.016 and p = 0.001). Plasma C-reactive protein correlated with plasma 24-HC (r = 0.51; p = 0.010), 25-HC (r = 0.75; p < 0.001), 27-HC (r = 0.48; p = 0.015), and with tissue 24S-HC (r = 0.4; p = 0.041) and 27-HC (r = 0.46; p = 0.023). Conclusion. Arterial intima accumulation of 27-HC and 24S-HC is associated with advanced atherosclerotic disease and systemic inflammatory activity in individuals with severe PAD.492199203Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)CNPq [300313/2007-1]FAPESP [2006/60585-9]CNPq [471380/2008-13