复制研究揭示 miR-483-5p 是预防心脏代谢疾病的重要靶点。
Replication study reveals miR-483-5p as an important target in prevention of cardiometabolic disease.
机构信息
Department of Clinical Sciences-Malmö, Hypertension and Cardiovascular Disease, Lund University, 205 02, Malmö, Sweden.
Department of Clinical Sciences Malmö, Lund University Diabetes Centre, Lund University Malmö, Malmö, Sweden.
出版信息
BMC Cardiovasc Disord. 2021 Apr 1;21(1):162. doi: 10.1186/s12872-021-01964-0.
BACKGROUND
Alterations in levels of circulating micro-RNAs might reflect within organ signaling or subclinical tissue injury that is linked to risk of diabetes and cardiovascular risk. We previously found that serum levels of miR-483-5p is correlated with cardiometabolic risk factors and incidence of cardiometabolic disease in a case-control sample from the populations-based Malmö Diet and Cancer Study Cardiovascular Cohort (MDC-CC). We here aimed at replicating these findings and to test for association with carotid atherosclerosis.
METHODS
We measured miR-483-5p in fasting serum of 1223 healthy subjects from the baseline examination of the population-based, prospective cohort study Malmö Offspring Study (MOS) and correlated miR-483-5p to cardiometabolic risk factors and to incidence of diabetes mellitus and coronary artery disease (CAD) during 3.7 (± 1.3) years of follow-up using logistic regression. In both MOS and MDC-CC we related mir-483-5p to carotid atherosclerosis measured with ultrasound.
RESULTS
In cross-sectional analysis miR-483-5p was correlated with BMI, waist circumference, HDL, and sex. After adjustment for age and sex, the association remained significant for all risk factors except for HDL. Logistic regression analysis showed significant associations between miR-483-5p and new-onset diabetes (OR = 1.94, 95% CI 1.06-3.56, p = 0.032) and cardiovascular disease (OR = 1.99, 95% CI 1.06-3.75, p = 0.033) during 3.7 (± 1.3) years of follow-up. Furthermore, miR-483-5p was significantly related with maximum intima-media thickness of the carotid bulb in MDC-CC (p = 0.001), but not in MOS, whereas it was associated with increasing number of plaques in MOS (p = 0.007).
CONCLUSION
miR-483-5p is related to an unfavorable cardiometabolic risk factor profile and predicts diabetes and CAD, possibly through an effect on atherosclerosis. Our results encourage further studies of possible underlying mechanisms and means of modifying miR-483-5p as a possible interventional target in prevention of cardiometabolic disease.
背景
循环 microRNA 水平的改变可能反映了器官内信号或与糖尿病和心血管风险相关的亚临床组织损伤。我们之前发现，血清 miR-483-5p 水平与基于人群的马尔默饮食与癌症研究心血管队列（MDC-CC）中的病例对照样本中的心血管代谢危险因素和心血管代谢疾病的发病率相关。在此，我们旨在复制这些发现，并检测其与颈动脉粥样硬化的关联。
方法
我们测量了来自基于人群的前瞻性队列研究马尔默后代研究（MOS）基线检查的 1223 名健康受试者的空腹血清中的 miR-483-5p，并使用逻辑回归分析 miR-483-5p 与心血管代谢危险因素以及 3.7（±1.3）年随访期间糖尿病和冠心病（CAD）的发病率之间的相关性。在 MOS 和 MDC-CC 中，我们将 mir-483-5p 与超声测量的颈动脉粥样硬化相关联。
结果
在横断面分析中，miR-483-5p 与 BMI、腰围、HDL 和性别相关。在校正年龄和性别后，除了 HDL 之外，所有危险因素的相关性仍然显著。逻辑回归分析显示，miR-483-5p 与新发糖尿病（OR=1.94，95%CI 1.06-3.56，p=0.032）和心血管疾病（OR=1.99，95%CI 1.06-3.75，p=0.033）之间存在显著相关性在 3.7（±1.3）年的随访期间。此外，miR-483-5p 与 MDC-CC 颈动脉球部内膜-中膜最大厚度显著相关（p=0.001），但在 MOS 中不相关，而在 MOS 中与斑块数量增加相关（p=0.007）。
结论
miR-483-5p 与不良的心血管代谢危险因素谱相关，并预测糖尿病和 CAD，可能通过对动脉粥样硬化的影响。我们的研究结果鼓励进一步研究潜在的机制和改变 miR-483-5p 的方法，作为预防心血管代谢疾病的可能干预靶点。
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