Schwertner Harvey A, Vítek Libor
Clinical Research, Wilford Hall Medical Center, San Antonio, TX 78236, USA.
Atherosclerosis. 2008 May;198(1):1-11. doi: 10.1016/j.atherosclerosis.2008.01.001. Epub 2008 Mar 17.
Serum bilirubin has been shown to be inversely related to cardiovascular disease (CVD) in both retrospective and prospective studies. Meta-analysis of existing studies has also confirmed that serum bilirubin concentrations are inversely related to CVD. Less information is known about the protective effects of slightly elevated serum bilirubin concentrations. In this review, we will focus primarily on the association of serum bilirubin and CVD and the possible protective roles of bilirubin, heme oxygenase (HO), and bilirubin UDP-glucuronosyltransferase (UGT1A1). HO and biliverdin reductase control the formation of bilirubin, whereas UGT1A1 controls bilirubin conjugation and clearance. Because of the health and therapeutic implications of slightly elevated serum bilirubin concentrations, we will discuss the recent prospective studies on cardiovascular risk in individuals with Gilbert syndrome (GS) as well as those with the UGT1A1*28 allele. Such individuals have decreased hepatic bilirubin UDP-glucuronosyltransferase activity, decreased bilirubin clearance, and increased serum bilirubin concentrations. Lastly, we will discuss some of the therapeutic approaches that could be used to increase serum bilirubin concentrations to prevent CVD and other oxidative and inflammatory diseases.
在回顾性和前瞻性研究中，血清胆红素均已显示出与心血管疾病（CVD）呈负相关。对现有研究的荟萃分析也证实，血清胆红素浓度与心血管疾病呈负相关。关于血清胆红素浓度轻度升高的保护作用，人们了解得较少。在本综述中，我们将主要关注血清胆红素与心血管疾病的关联以及胆红素、血红素加氧酶（HO）和胆红素UDP-葡萄糖醛酸基转移酶（UGT1A1）可能的保护作用。HO和胆绿素还原酶控制胆红素的形成，而UGT1A1控制胆红素的结合和清除。鉴于血清胆红素浓度轻度升高对健康和治疗的影响，我们将讨论近期关于吉尔伯特综合征（GS）患者以及携带UGT1A1*28等位基因者心血管风险的前瞻性研究。此类个体肝胆红素UDP-葡萄糖醛酸基转移酶活性降低、胆红素清除减少且血清胆红素浓度升高。最后，我们将讨论一些可用于提高血清胆红素浓度以预防心血管疾病及其他氧化和炎症性疾病的治疗方法。
