Mnguni Ayanda Trevor, Engel Mark E, Borkum Megan S, Mayosi Bongani M
Department of Medicine, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa.
PLoS One. 2015 Dec 11;10(12):e0143338. doi: 10.1371/journal.pone.0143338. eCollection 2015.
Tuberculous pericardial effusion is a pro-fibrotic condition that is complicated by constrictive pericarditis in 4% to 8% of cases. N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a ubiquitous tetrapeptide with anti-fibrotic properties that is low in tuberculous pericardial effusion, thus providing a potential mechanism for the heightened fibrotic state. Angiotensin-converting enzyme inhibitors (ACE-I), which increase Ac-SDKP levels with anti-fibrotic effects in animal models, are candidate drugs for preventing constrictive pericarditis if they can be shown to have similar effects on Ac-SDKP and fibrosis in human tissues.
To systematically review the effects of ACE-Is on Ac-SDKP levels in human tissues.
We searched five electronic databases (1996 to 2014) and conference abstracts with no language restrictions. Two reviewers independently selected studies, extracted data and assessed methodological quality. The protocol was registered in PROSPERO.
Four studies with a total of 206 participants met the inclusion criteria. Three studies (106 participants) assessed the change in plasma levels of Ac-SDKP following ACE-I administration in healthy humans. The administration of an ACE-I was associated with an increase in Ac-SDKP levels (mean difference (MD) 5.07 pmol/ml (95% confidence intervals (CI) 0.64 pmol/ml to 9.51 pmol/ml)). Two studies with 100 participants further assessed the change in Ac-SDKP level in humans with renal failure using ACE-I. The administration of an ACE-I was associated with a significant increase in Ac-SDKP levels (MD 8.94 pmol/ml; 95% CI 2.55 to 15.33; I2 = 44%).
ACE-I increased Ac-SDKP levels in human plasma. These findings provide the rationale for testing the impact of ACE-I on Ac-SDKP levels and fibrosis in tuberculous pericarditis.
结核性心包积液是一种促纤维化病症，4%至8%的病例会并发缩窄性心包炎。N-乙酰丝氨酰-天冬氨酰-赖氨酰-脯氨酸（Ac-SDKP）是一种普遍存在的具有抗纤维化特性的四肽，在结核性心包积液中含量较低，这为纤维化状态加剧提供了一种潜在机制。血管紧张素转换酶抑制剂（ACE-I）在动物模型中可提高Ac-SDKP水平并具有抗纤维化作用，如果能证明其对人体组织中的Ac-SDKP和纤维化有类似影响，那么它就是预防缩窄性心包炎的候选药物。
系统评价ACE-I对人体组织中Ac-SDKP水平的影响。
检索五个电子数据库（1996年至2014年）以及会议摘要，无语言限制。两名评价员独立选择研究、提取数据并评估方法学质量。研究方案已在国际前瞻性系统评价注册库（PROSPERO）登记。
四项研究共206名参与者符合纳入标准。三项研究（106名参与者）评估了健康人服用ACE-I后血浆中Ac-SDKP水平的变化。服用ACE-I与Ac-SDKP水平升高相关（平均差（MD）5.07 pmol/ml（95%置信区间（CI）0.64 pmol/ml至9.51 pmol/ml））。两项研究共100名参与者进一步评估了使用ACE-I的肾衰竭患者体内Ac-SDKP水平的变化。服用ACE-I与Ac-SDKP水平显著升高相关（MD 8.94 pmol/ml；95% CI 2.55至15.33；I² = 44%）。
ACE-I可提高人体血浆中Ac-SDKP水平。这些发现为测试ACE-I对结核性心包炎中Ac-SDKP水平和纤维化的影响提供了理论依据。
