Yang Vicky K, Loughran Kerry A, Meola Dawn M, Juhr Christine M, Thane Kristen E, Davis Airiel M, Hoffman Andrew M
Department of Clinics Sciences, Tufts University Cummings School of Veterinary Medicine, North Grafton, USA.
J Extracell Vesicles. 2017 Jul 12;6(1):1350088. doi: 10.1080/20013078.2017.1350088. eCollection 2017.
Myxomatous mitral valve disease (MMVD) is functionally and histologically identical to mitral valve prolapse (MVP) in humans. Currently, there are no medical treatments that can delay the progression of this valvular disease or associated cardiac remodelling. Therefore, there is a need to understand the molecular pathology associated with MMVD and MVP better, and thus identify potential therapeutic targets. Circulating exosomes contain small RNA, including miRNA, which reflect cell physiology and pathology. This study explored the association between circulating exosomal miRNA (ex-miRNA) content and MMVD, heart failure due to MMVD (MMVD-CHF) and ageing, which is strongly associated with MMVD. Ex-miRNA was isolated from old normal/healthy dogs ( = 6), young normal dogs ( = 7), dogs with MMVD ( = 7) and dogs with MMVD-CHF ( = 7). Separately, total plasma miRNA was isolated from normal dogs ( = 8), dogs with MMVD ( = 8) and dogs with MMVD-CHF ( = 11). Using reverse transcription quantitative polymerase chain reaction, exosomal miR-181c ( = 0.003) and miR-495 ( = 0.0001) significantly increased in dogs with MMVD-CHF compared to the other three groups. Exosomal miR-9 ( = 0.002) increased in dogs with MMVD and MMVD-CHF compared to age-matched (old) normal dogs. Exosomal miR-599 ( = 0.002) decreased in dogs with MMVD compared to old normal dogs. In total plasma, 58 miRNA were deemed significantly different ( < 0.04) between normal dogs, dogs with MMVD and dogs with MMVD-CHF. However, in contrast to ex-miRNA, none of the miRNA in total plasma remained statistically significant if the false discovery rate was <15%. Changes in ex-miRNA are observed in dogs as they age (miR-9, miR-495 and miR-599), develop MMVD (miR-9 and miR-599) and progress from MMVD to CHF (miR-181c and miR-495). Ex-miRNA expression-level changes appear to be more specific to disease states than total plasma miRNA. Elena Aikawa, Harvard Medical School, USA.
黏液瘤样二尖瓣疾病（MMVD）在功能和组织学上与人类的二尖瓣脱垂（MVP）相同。目前，尚无能够延缓这种瓣膜疾病进展或相关心脏重塑的医学治疗方法。因此，有必要更好地了解与MMVD和MVP相关的分子病理学，从而确定潜在的治疗靶点。循环外泌体含有小RNA，包括miRNA，它们反映细胞的生理和病理状态。本研究探讨了循环外泌体miRNA（ex-miRNA）含量与MMVD、MMVD所致心力衰竭（MMVD-CHF）以及与MMVD密切相关的衰老之间的关联。从老年正常/健康犬（n = 6）、年轻正常犬（n = 7）、患有MMVD的犬（n = 7）和患有MMVD-CHF的犬（n = 7）中分离出ex-miRNA。另外，从正常犬（n = 8）、患有MMVD的犬（n = 8）和患有MMVD-CHF的犬（n = 11）中分离出总血浆miRNA。使用逆转录定量聚合酶链反应，与其他三组相比，患有MMVD-CHF的犬的外泌体miR-181c（P = 0.003）和miR-495（P = 0.0001）显著增加。与年龄匹配的（老年）正常犬相比，患有MMVD和MMVD-CHF的犬的外泌体miR-9（P = 0.002）增加。与老年正常犬相比，患有MMVD的犬的外泌体miR-599（P = 0.002）减少。在总血浆中，正常犬、患有MMVD的犬和患有MMVD-CHF的犬之间有58种miRNA被认为有显著差异（P < 0.04）。然而，与ex-miRNA相反，如果错误发现率<15%，总血浆中的miRNA均无统计学意义。随着犬年龄增长（miR-9、miR-495和miR-599）、发展为MMVD（miR-9和miR-599）以及从MMVD进展为CHF（miR-181c和miR-495），可观察到ex-miRNA的变化。与总血浆miRNA相比，ex-miRNA表达水平的变化似乎对疾病状态更具特异性。 埃琳娜·爱川，美国哈佛医学院
