Stec David E, Hosick Peter A, Granger Joey P
Department of Physiology and Biophysics, Center for Excellence in Cardiovascular - Renal Research, University of Mississippi Medical Center Jackson, MS, USA.
Front Pharmacol. 2012 Feb 14;3:18. doi: 10.3389/fphar.2012.00018. eCollection 2012.
Bilirubin is generated from the breakdown of heme by heme oxygenase and the reduction of biliverdin by the enzyme biliverdin reductase. Several large population studies have reported a significant inverse correlation between plasma bilirubin levels and the incidence of cardiovascular disease. Protection from cardiovascular disease is also observed in patients with Gilbert's syndrome which is a disease characterized by mutations in hepatic UGT1A1, the enzyme responsible for the conjugation of bilirubin into the bile. Despite the strong correlation between plasma bilirubin levels and the protection from cardiovascular disease, the mechanism by which increases in plasma bilirubin acts to protect against cardiovascular disease is unknown. Since the chronic antihypertensive actions of bilirubin are likely due to its renal actions, the effects of moderate increases in plasma bilirubin on renal hemodynamics as well as bilirubin's potential effects on renal tubule function will be discussed in this review. Mechanisms of action as well as the potential for antihypertensive therapies targeting moderate increases in plasma bilirubin levels will also be highlighted.
胆红素由血红素加氧酶催化血红素分解以及胆绿素还原酶还原胆绿素产生。多项大型人群研究报告称,血浆胆红素水平与心血管疾病发病率之间存在显著负相关。在吉尔伯特综合征患者中也观察到对心血管疾病的保护作用,该综合征是一种因肝脏UGT1A1(负责将胆红素结合到胆汁中的酶)突变而导致的疾病。尽管血浆胆红素水平与预防心血管疾病之间存在密切关联,但血浆胆红素升高发挥心血管疾病预防作用的机制尚不清楚。由于胆红素的慢性降压作用可能归因于其对肾脏的作用,本综述将讨论血浆胆红素适度升高对肾脏血流动力学的影响以及胆红素对肾小管功能的潜在作用。还将重点介绍作用机制以及针对血浆胆红素水平适度升高的降压治疗潜力。