Graessler Juergen, Schwudke Dominik, Schwarz Peter E H, Herzog Ronny, Shevchenko Andrej, Bornstein Stefan R
Department of Internal Medicine III, Carl Gustav Carus Medical School, Technical University Dresden, Dresden, Germany.
PLoS One. 2009 Jul 15;4(7):e6261. doi: 10.1371/journal.pone.0006261.
Dyslipoproteinemia, obesity and insulin resistance are integrative constituents of the metabolic syndrome and are major risk factors for hypertension. The objective of this study was to determine whether hypertension specifically affects the plasma lipidome independently and differently from the effects induced by obesity and insulin resistance.
METHODOLOGY/PRINCIPAL FINDINGS: We screened the plasma lipidome of 19 men with hypertension and 51 normotensive male controls by top-down shotgun profiling on a LTQ Orbitrap hybrid mass spectrometer. The analysis encompassed 95 lipid species of 10 major lipid classes. Obesity resulted in generally higher lipid load in blood plasma, while the content of tri- and diacylglycerols increased dramatically. Insulin resistance, defined by HOMA-IR >3.5 and controlled for BMI, had little effect on the plasma lipidome. Importantly, we observed that in blood plasma of hypertensive individuals the overall content of ether lipids decreased. Ether phosphatidylcholines and ether phosphatidylethanolamines, that comprise arachidonic (20:4) and docosapentaenoic (22:5) fatty acid moieties, were specifically diminished. The content of free cholesterol also decreased, although conventional clinical lipid homeostasis indices remained unaffected.
CONCLUSIONS/SIGNIFICANCE: Top-down shotgun lipidomics demonstrated that hypertension is accompanied by specific reduction of the content of ether lipids and free cholesterol that occurred independently of lipidomic alterations induced by obesity and insulin resistance. These results may form the basis for novel preventive and dietary strategies alleviating the severity of hypertension.
血脂异常、肥胖和胰岛素抵抗是代谢综合征的综合组成部分，也是高血压的主要危险因素。本研究的目的是确定高血压是否独立且不同于肥胖和胰岛素抵抗所诱导的效应，对血浆脂质组产生特异性影响。
方法/主要发现：我们使用LTQ Orbitrap混合质谱仪，通过自上而下的鸟枪法分析，对19名高血压男性和51名血压正常的男性对照者的血浆脂质组进行了筛查。分析涵盖了10种主要脂质类别的95种脂质。肥胖通常导致血浆中脂质负荷更高，而三酰甘油和二酰甘油的含量急剧增加。以HOMA-IR>3.5定义并校正BMI后的胰岛素抵抗，对血浆脂质组影响不大。重要的是，我们观察到高血压个体血浆中醚脂的总体含量降低。包含花生四烯酸（20:4）和二十二碳五烯酸（22:5）脂肪酸部分的醚磷脂酰胆碱和醚磷脂酰乙醇胺含量尤其减少。尽管传统临床脂质稳态指标未受影响，但游离胆固醇含量也降低了。
结论/意义：自上而下的鸟枪法脂质组学表明，高血压伴随着醚脂和游离胆固醇含量的特异性降低，这一现象独立于肥胖和胰岛素抵抗所引起的脂质组改变。这些结果可能为减轻高血压严重程度的新型预防和饮食策略奠定基础。
