Smoking-induced generation of oxidized phospholipids and the effect of deficiency of hydrolyzing enzyme for oxidatively modified phospholipids : role of the enzyme deficiency in carcinogenesis and vascular injury.

血小板活化因子（PAF）是一种生物活性磷脂，对白细胞、平滑肌细胞和神经细胞等多种细胞具有激动作用；它涉及到各种病理状况。醚类磷脂氧化产生具有sn-2短链残基的衍生物，这些衍生物也具有类似paf的生物活性。PAF乙酰水解酶（PAF- ah）可使PAF或类PAF脂质失活，并在血浆中发现高水平的活性。血浆PAF-AH缺乏症是由于基因（G994T）的错义突变引起的，据报道其在日本普通人群中的患病率约为4%。这种突变也被认为是中风或缺血性心脏病的遗传危险因素。在本研究中，我们首先发现血浆PAF-AH缺乏症的患病率在健康的习惯吸烟者和非吸烟者之间几乎相同。有高血压、糖尿病、高脂血症等血管疾病危险因素的受试者组（危险因素组）与没有这些危险因素的受试者组（正常组）相比，突变基因的患病率没有显著差异。而在基因型正常的受试者中，危险因素组的PAF-AH活性高于正常组。杂合子基因型的受试者没有观察到这种差异。其次，我们在吸完香烟后不久获得的血浆脂质提取物中检测到聚集活性，并且这种活性在薄层色谱中与真正的PAF共迁移。我们得出结论，血浆PAF-AH在各种疾病中增加，包括慢性生活方式疾病，作为一种过继机制，这种酶的缺乏可能与疾病风险增加有关。

Platelet-activating factor (PAF) is a bioactive phospholipid that has agonistic activities towards many types of cells such as white blood cells, smooth muscle cells, and neuronal cells ; and it is implicated various pathological conditions. Oxidation of ether phospholipids results in the generation of derivatives with a sn-2 short chain residue, and such derivatives also acquire PAF-like bioactivities. PAF or PAD-like lipids are inactivated by PAF acetylhydrolase (PAF-AH), and a high level of activity is found in plasma. Plasma PAF-AH deficiency is due to a missense mutation in the gene (G994T) and its prevalence among a general Japanese population is reported to be about 4%. This mutation is also known to be a genetic risk factor of stroke or ischemic heart disease.In the present study, we first found that the prevalence of plasma PAF-AH deficiency is virtually the same between healthy habitual smokers and non-smokers. There was no significant difference in the prevalence of the mutant gene between the group of the subjects who have risk factors for vascular diseases such as hypertension, diabetes mellitus, or hyperlipidemia (risk factor group) as compared to the group without such risk factors (normal group). However, among the subjects with normal genotype, the risk factor group had higher PAF-AH activity than the normal group. Such a difference was not observed for the subjects with the heterozygous genotype. Secondly, we detected an aggregating activity in lipid extracts of plasma obtained shortly after smoking cigarettes, and such activity co-migrated with authentic PAF in thin-layer chromatography.We conclude that plasma PAF-AH is increased in various diseases, including chronic lifestyle diseases, as an adoptive mechanism and the deficiency of this enzyme may be associated with enhanced risk for the diseases.