Université de Lorraine, INSERM, Centre d'Investigations Cliniques Plurithématique 1433, INSERM U1116, CHRU de Nancy, F-CRIN INI-CRCT, Nancy, France; Department of Cardiology, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
Université de Lorraine, INSERM, Centre d'Investigations Cliniques Plurithématique 1433, INSERM U1116, CHRU de Nancy, F-CRIN INI-CRCT, Nancy, France; Cardiovascular Research and Development Unit (UnIC), Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal.
Int J Cardiol. 2021 Jun 1;332:35-37. doi: 10.1016/j.ijcard.2021.02.088. Epub 2021 Mar 5.
After myocardial infarction (MI) complicated by heart failure (HF), eplerenone reduced serum concentrations of amino-terminal propeptide of type III collagen (PIIINP) and carboxy-terminal propeptide of type I collagen (PICP). Determining a subgroup who are more prone to decrease their collagen content and to respond better to the antifibrotic effects of mineralocorticoid receptor antagonists (MRA) may be relevant for a personalized treatment approach. Whether circulating microRNAs may identify a subgroup that have experienced a more pronounced antifibrotic effect of eplerenone as measured by a PICP and PIIINP decrease is unclear.
A set of circulating microRNAs linked to cardiac fibrosis (mir-1, mir-21, mir-29a, mir-29b, mir-101, mir-122, mir-133a) were measured at baseline in 198 patients in the biomarker substudy of Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). Associations between baseline microRNA levels and changes in both PIIINP and PICP from baseline to month 9 were studied using multivariable analysis of covariance, adjusting for age, sex, history of hypertension and diabetes mellitus, prescription of ACE-inhibitors or angiotensin receptor blockers, baseline PIIINP or PICP, and eplerenone treatment. Furthermore, a treatment-by-microRNA interaction was studied.
From the selected microRNAs, only mir-133a was associated with a PICP decrease (ß-6.43, 95%CI-12.71 to -0.15,p = 0.045). None of the microRNAs was associated with a PIIINP change. The microRNAs did not predict an effect of eplerenone on PICP and PIIINP changes.
Although serum mir-133a was associated with PICP change, none of the microRNAs previously linked to cardiac fibrosis predicted an antifibrotic response to eplerenone. Further study is needed to identify other suitable targets for a personalized treatment approach.
心肌梗死后并发心力衰竭（HF）后，依普利酮降低了氨基末端前肽 III 型胶原（PIIINP）和羧基末端前肽 I 型胶原（PICP）的血清浓度。确定一个更倾向于降低胶原含量并对盐皮质激素受体拮抗剂（MRA）的抗纤维化作用有更好反应的亚组可能与个性化治疗方法相关。循环 microRNA 是否可以识别出一组患者，通过 PICP 和 PIIINP 降低来衡量，他们经历了依普利酮更明显的抗纤维化作用尚不清楚。
在 Eplerenone 急性心肌梗死后心力衰竭疗效和生存研究（EPHESUS）的生物标志物子研究中，198 例患者在基线时检测了一组与心脏纤维化相关的循环 microRNA（mir-1、mir-21、mir-29a、mir-29b、mir-101、mir-122、mir-133a）。使用协方差的多变量分析，调整年龄、性别、高血压和糖尿病病史、ACE 抑制剂或血管紧张素受体阻滞剂的处方、基线 PIIINP 或 PICP 以及依普利酮治疗，研究了基线 microRNA 水平与基线至 9 个月时的 PIIINP 和 PICP 变化之间的关系。此外，还研究了治疗与 microRNA 之间的相互作用。
在所选择的 microRNA 中，只有 mir-133a 与 PICP 降低相关（β-6.43，95%CI-12.71 至-0.15，p=0.045）。没有 microRNA 与 PIIINP 变化相关。这些 microRNA 不能预测依普利酮对 PICP 和 PIIINP 变化的影响。
虽然血清 mir-133a 与 PICP 变化相关，但之前与心脏纤维化相关的 microRNA 均不能预测依普利酮的抗纤维化反应。需要进一步研究以确定其他适合个性化治疗方法的合适靶点。
