Wysokinski Waldemar E, Tafur Alfonso, Ammash Naser, Asirvatham Samuel J, Wu Yanhong, Gosk-Bierska Izabella, Grill Diane E, Slusser Joshua P, Mruk Jozef, McBane Robert D
Mayo Clinic and Foundation for Education and Research, Rochester, MN, USA.
Department of Cardiovascular Medicine, Vascular Surgery and Medicine Section, NorthShore University HealthSystem, Skokie, USA.
Eur J Haematol. 2017 Jun;98(6):615-621. doi: 10.1111/ejh.12879. Epub 2017 Apr 20.
Platelets retain cytoplasmic messenger RNA and are capable of protein biosynthesis. Several diseases are known to impact the platelet transcriptome but the effect of non-valvular atrial fibrillation (NVAF) on platelet RNA transcript is essentially unknown. The aim of this study was to evaluate the impact of NVAF on platelet RNA transcript by measuring platelet genes expression in consecutive NVAF patients before and 3-4 months after pulmonary vein isolation (PVI) and compared to normal sinus rhythm controls (NSR).
RNA from isolated platelets were reverse transcribed, assayed against 15 genes using real-time qPCR, and expressed as mean cycle threshold (ΔCt) using beta-2-microglobulin as endogenous control. Expression of all evaluated genes, except cathepsin A gene, was significantly lower (higher ΔCt) in 103 NVAF patients compared to 55 NSR controls. Insulin-like growth factor binding protein acid labile subunit gene (IGFALS) had expression more than 16 fold-lower (17.0±2.8 vs 12.5±3.8, P<.001), follow by genes encoding for prostacyclin receptor, and for von Willebrand factor which had fourfold lower expression compared to NSR controls. Gender, type of atrial fibrillation, heart failure, hypertension, prior stroke, diabetes mellitus, and atherosclerosis were associated with different gene expression. Following PVI, expression of four genes significantly increased, particularly IGFALS gene (increased 256-fold) and ADAMT gene increased 16-fold); expression of three genes significantly decreased, and expression of eight genes has not changed.
Platelets are capable to respond to the circulatory environment of NVAF by altering transcript and changing prothrombotic status. This shows platelet potential for molecular "reprogramming" possibly induced by flow disturbances of NVAF.
血小板保留细胞质信使核糖核酸并能够进行蛋白质生物合成。已知几种疾病会影响血小板转录组，但非瓣膜性心房颤动（NVAF）对血小板RNA转录本的影响基本上未知。本研究的目的是通过测量连续的NVAF患者在肺静脉隔离（PVI）前和3-4个月后的血小板基因表达，并与正常窦性心律对照组（NSR）进行比较，来评估NVAF对血小板RNA转录本的影响。
从分离的血小板中提取RNA进行逆转录，使用实时定量聚合酶链反应针对15个基因进行检测，并以内源性对照β-2-微球蛋白表示为平均循环阈值（ΔCt）。与55名NSR对照组相比，103名NVAF患者中除组织蛋白酶A基因外，所有评估基因的表达均显著降低（ΔCt值更高）。胰岛素样生长因子结合蛋白酸性不稳定亚基基因（IGFALS）的表达降低超过16倍（17.0±2.8对12.5±3.8，P<0.001），其次是前列环素受体编码基因和血管性血友病因子编码基因，其表达比NSR对照组降低了四倍。性别、心房颤动类型、心力衰竭、高血压、既往中风、糖尿病和动脉粥样硬化与不同的基因表达相关。PVI后，四个基因的表达显著增加，特别是IGFALS基因（增加256倍）和ADAMT基因增加16倍；三个基因的表达显著降低，八个基因的表达未改变。
血小板能够通过改变转录本和改变血栓前状态来响应NVAF的循环环境。这表明血小板可能因NVAF的血流紊乱而具有分子“重编程”的潜力。
