Division of Endocrinology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA.
Br J Pharmacol. 2017 Nov;174(22):3986-4006. doi: 10.1111/bph.13743. Epub 2017 Mar 23.
Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide. Inflammatory processes arising from metabolic abnormalities are known to precipitate the development of CVD. Several metabolic and inflammatory markers have been proposed for predicting the progression of CVD, including high density lipoprotein cholesterol (HDL-C). For ~50 years, HDL-C has been considered as the atheroprotective 'good' cholesterol because of its strong inverse association with the progression of CVD. Thus, interventions to increase the concentration of HDL-C have been successfully tested in animals; however, clinical trials were unable to confirm the cardiovascular benefits of pharmaceutical interventions aimed at increasing HDL-C levels. Based on these data, the significance of HDL-C in the prevention of CVD has been called into question. Fundamental in vitro and animal studies suggest that HDL-C functionality, rather than HDL-C concentration, is important for the CVD-preventive qualities of HDL-C. Our current review of the literature positively demonstrates the negative impact of systemic and tissue (i.e. adipose tissue) inflammation in the healthy metabolism and function of HDL-C. Our survey indicates that HDL-C may be a good marker of adipose tissue health, independently of its atheroprotective associations. We summarize the current findings on the use of anti-inflammatory drugs to either prevent HDL-C clearance or improve the function and production of HDL-C particles. It is evident that the therapeutic agents currently available may not provide the optimal strategy for altering HDL-C metabolism and function, and thus, further research is required to supplement this mechanistic approach for preventing the progression of CVD.
This article is part of a themed section on Targeting Inflammation to Reduce Cardiovascular Disease Risk. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.22/issuetoc and http://onlinelibrary.wiley.com/doi/10.1111/bcp.v82.4/issuetoc.
心血管疾病（CVD）是全世界发病率和死亡率的主要原因。已知代谢异常引起的炎症过程会引发 CVD 的发展。已经提出了几种代谢和炎症标志物来预测 CVD 的进展，包括高密度脂蛋白胆固醇（HDL-C）。大约 50 年来，由于其与 CVD 进展呈强烈负相关，HDL-C 一直被认为是具有保护作用的“好”胆固醇。因此，已经在动物中成功测试了增加 HDL-C 浓度的干预措施；然而，临床试验无法证实旨在增加 HDL-C 水平的药物干预的心血管益处。基于这些数据，HDL-C 在预防 CVD 中的意义受到质疑。基础的体外和动物研究表明，HDL-C 的功能而不是浓度对于 HDL-C 的 CVD 预防特性很重要。我们对文献的当前综述积极证明了全身和组织（即脂肪组织）炎症对 HDL-C 的健康代谢和功能的负面影响。我们的调查表明，HDL-C 可能是脂肪组织健康的良好标志物，与其抗动脉粥样硬化的关联无关。我们总结了目前关于使用抗炎药物预防 HDL-C 清除或改善 HDL-C 颗粒功能和产生的研究结果。显然，目前可用的治疗剂可能无法提供改变 HDL-C 代谢和功能的最佳策略，因此需要进一步研究来补充这种预防 CVD 进展的机制方法。
本文是关于靶向炎症以降低心血管疾病风险的专题部分的一部分。要查看本节中的其他文章，请访问 http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.22/issuetoc 和 http://onlinelibrary.wiley.com/doi/10.1111/bcp.v82.4/issuetoc。
