Paraoxonases : Structure, gene polymorphism & role in coronary artery disease.

Paraoxonases (PONs) i.e. PON1, PON2, PON3 are basically lactonases. Of these, PON1 in addition has an efficient esterase activity and can hydrolyze organophosphates. The PONs prevent low density lipoprotein cholesterol (LDL-C) from peroxidation, thereby preventing atherosclerosis. The PON1 is exclusively associated with high density lipoprotein cholesterol (HDL-C) and its antioxidant activity is largely attributed to PON1 located on it. At present, PON1 status i.e. its activity and concentration, is considered to be more important than polymorphism alone, in prevention of coronary artery disease (CAD). Its activity has been found to be affected by a number of pharmacological agents, diet and other factors, thereby becoming a promising target for pharmacological intervention. The PON2 prevents cell mediated lipid peroxidation. However, little is known about the role of PON3. This review describes the structure, gene polymorphism, and factors affecting the activity of PONs, and their role in prevention of CAD.

Alterations in lipid transfer to High-Density Lipoprotein (HDL) and activity of paraoxonase-1 in HIV+ patients / Alterações na transferência de lípides para a lipoproteína de alta densidade (HDL) e atividade da paroxonase 1 em pacientes HIV+

HIV+ patients often develop alterations of the plasma lipids that may implicate in development of premature coronary artery disease. High-density lipoprotein (HDL) has an important role in preventing atherogenesis and the aim of this study was to investigate aspects of HDL function in HIV+ patients. HIV+ patients (n = 48) and healthy control subjects (n = 45) of both sexes with similar age were studied. Twenty-five were not being treated with antiretroviral agents, 13 were under reverse transcriptase inhibitor nucleosidic and non-nucleosidic (NRTI+NNRTI) and 10 were under NRTI + protease inhibitors (NRTI+PI) treatment. Paraoxonase 1 (PON1) activity and the transfer of free and esterified cholesterol, tryglicerides and phospholipids from a lipidic nanoemulsion to HDL were analyzed. In comparison with healthy controls, HIV+ patients presented low PON-1 activity and diminished transfer of free cholesterol and tryglicerides. In contrast, phospholipid transfer was increased in those patients, whereas the transfer of cholesteryl esters was unchanged. NRTI+NNRTI increases the transfer of cholesteryl esters and triglycerides but in NRTI+PI there was no difference in respect to non-treated HIV+ patients. HDL from HIV+ patients has smaller antioxidant properties, as shown by lower PON-1 activity, and the transfer of lipids to this lipoprotein fraction is also altered, suggesting that HDL function is defective in those patients.

Pacientes HIV+ freqüentemente desenvolvem alterações no metabolismo de lípides que podem influir no desenvolvimento de doença arterial coronária. A lipoproteína de alta densidade (HDL) tem papel importante na prevenção da aterogênese. Para investigar aspectos funcionais da HDL na doença, foram estudados 48 pacientes HIV+ e 45 indivíduos-controle saudáveis de ambos os sexos, com idade semelhantes. Vinte e cinco pacientes HIV+ não recebiam terapia antirretroviral, 13 estavam sob tratamento com inibidores nucleosídicos de transcriptase reversa e não-nucleosídicos (NRTI+NNRTI) e 10 sob tratamento com NRTI e inibidor de protease (NRTI+PI). Analisou-se a atividade da paroxonase 1 e a transferência de colesterol livre e esterificado, triglicérides e fosfolipídios de uma nanoemulsão lipídica para a HDL. Pacientes HIV+ apresentaram menor atividade da paroxonase 1 e menor transferência de colesterol livre e triglicérides em relação aos indivíduos saudáveis. A transferência de fosfolipídios foi maior nesses pacientes, mas a transferência de éster de colesterol foi similar. NRTI+NNRTI aumenta a transferência de éster de colesterol e triglicérides, mas em NRTI+PI não houve diferença comparando com os pacientes HIV+ não tratados. A HDL de pacientes HIV+ tem propriedades antioxidantes reduzidas, evidenciada pela menor atividade da paraxonase 1, e transferência de lipídios alterada, sugerindo que a HDL apresente função defeituosa nestes pacientes.