Cardiovascular Diseases, Merck Research Laboratories, 126 E. Lincoln Ave., Rahway, NJ 07065, USA.
Lipids Health Dis. 2010 Jun 11;9:61. doi: 10.1186/1476-511X-9-61.
Cholesterol deposition in arterial wall drives atherosclerosis. The key goal of this study was to examine the relationship between plaque cholesterol content and patient characteristics that typically associate with disease state and lesion vulnerability. Quantitative assays for free cholesterol, cholesteryl ester, triglyceride, and protein markers in atherosclerotic plaque were established and applied to plaque samples from multiple patients and arterial beds (Carotid and peripheral arteries; 98 lesions in total).
We observed a lower cholesterol level in restenotic than primary peripheral plaque. We observed a trend toward a higher level in symptomatic than asymptomatic carotid plaque. Peripheral plaque from a group of well-managed diabetic patients displayed a weak trend of more free cholesterol deposition than plaque from non-diabetic patients. Plaque triglyceride content exhibited less difference in the same comparisons. We also measured cholesterol in multiple segments within one carotid plaque sample, and found that cholesterol content positively correlated with markers of plaque vulnerability, and negatively correlated with stability markers.
Our results offer important biological validation of cholesterol as a key lipid marker for plaque severity. Results also suggest cholesterol is a more sensitive plaque marker than routine histological staining for neutral lipids.
动脉壁中的胆固醇沉积会导致动脉粥样硬化。本研究的主要目的是检验斑块胆固醇含量与通常与疾病状态和病变易损性相关的患者特征之间的关系。建立了用于检测动脉粥样硬化斑块中游离胆固醇、胆固醇酯、甘油三酯和蛋白标志物的定量分析方法，并将其应用于来自多个患者和动脉床（颈动脉和外周动脉；共 98 个病变）的斑块样本中。
我们观察到再狭窄性外周斑块中的胆固醇水平低于原发性外周斑块。我们观察到症状性颈动脉斑块中的胆固醇水平呈上升趋势，而无症状颈动脉斑块中的胆固醇水平呈下降趋势。与非糖尿病患者相比，经过良好管理的糖尿病患者的外周斑块中游离胆固醇的沉积呈微弱趋势。在相同的比较中，斑块中的甘油三酯含量差异较小。我们还测量了一个颈动脉斑块样本中多个节段的胆固醇含量，发现胆固醇含量与斑块易损性标志物呈正相关，与稳定性标志物呈负相关。
我们的研究结果为胆固醇作为斑块严重程度的关键脂质标志物提供了重要的生物学验证。结果还表明，胆固醇作为斑块标志物比常规的中性脂质组织学染色更为敏感。
