Klett Eric L, Patel Shailesh
Division of Endocrinology, Diabetes and Medical Genetics, Medical University of South Carolina, Charleston, South Carolina 29403, USA.
Curr Opin Lipidol. 2003 Aug;14(4):341-5. doi: 10.1097/01.mol.0000083763.66245.18.
PURPOSE OF REVIEW This review discusses recent progress in the role of ATP-binding cassette proteins ABCG5 and G8 in dietary sterol absorption, excretion and pathogenesis of cardiovascular disease. RECENT FINDINGS Identification of the genetic defect(s) underlying sitosterolemia has led to a renewed interest in the mechanisms of sterol absorption and biliary excretion. Mutations in ABCG5 (encoding sterolin-1) or ABCG8 (encoding sterolin-2) cause this disease. These proteins are thought to function by preventing dietary noncholesterol sterols from being retained by the body and for cholesterol excretion into bile. SUMMARY Despite improvements in treatments for hypercholesterolemia with cholesterol lowering agents, cardiovascular disease still remains highly prevalent. This has prompted many to consider that molecules other than cholesterol may be better biomarkers for this disease and targeting these more directly may allow us to develop more effective therapies. Ideally, if such a biomarker were also the bioactive molecule that is key to initiating/propagating the atherosclerosis pathogenic pathway, this would allow us to develop an optimal predictor and monitor of the disease process. One source of such molecules could come from our diet, with potential candidates such as noncholesterol sterols, oxysterols, oxidized sterols or some as yet unidentified dietary bioactive molecule. Nature has evolved a protective mechanism by which such molecules are kept out of the body, thereby reducing the negative effects of these compounds. The newly identified sterolin proteins involved in the absorption and excretion of dietary sterols may fit this bill. If so, we would speculate that a better biomarker may be lurking within their substrate specificities.
综述目的 本综述讨论了ATP结合盒蛋白ABCG5和G8在膳食固醇吸收、排泄及心血管疾病发病机制中的作用的最新进展。
最新发现 对植物甾醇血症潜在遗传缺陷的鉴定引发了对固醇吸收和胆汁排泄机制的新关注。ABCG5（编码甾醇转运蛋白1）或ABCG8（编码甾醇转运蛋白2）的突变会导致这种疾病。这些蛋白被认为通过阻止膳食中的非胆固醇固醇被身体保留以及促进胆固醇排泄到胆汁中发挥作用。
总结 尽管使用降胆固醇药物治疗高胆固醇血症有了改善，但心血管疾病仍然非常普遍。这促使许多人认为，除胆固醇外的其他分子可能是这种疾病更好的生物标志物，更直接地针对这些分子可能使我们开发出更有效的治疗方法。理想情况下，如果这样的生物标志物也是启动/传播动脉粥样硬化致病途径的关键生物活性分子，这将使我们能够开发出疾病进程的最佳预测指标和监测指标。这类分子的一个来源可能是我们的饮食，潜在候选物如非胆固醇固醇、氧化固醇、氧化甾醇或一些尚未确定的膳食生物活性分子。大自然进化出了一种保护机制，通过这种机制这些分子被排除在体外，从而减少这些化合物的负面影响。新发现的参与膳食固醇吸收和排泄的甾醇转运蛋白可能符合这一要求。如果是这样，我们推测在它们的底物特异性中可能潜藏着更好的生物标志物。
