Atrial fibrillation in pigs induces left atrial endocardial transcriptional remodelling

被引:7
|
作者
Cervero, Jorge [1 ]
Segura, Victor [2 ]
Macias, Alfonso [3 ]
Jose Gavira, Juan [3 ]
Montes, Ramon [1 ]
Hermida, Jose [1 ]
机构
[1] Univ Navarra, Div Cardiovasc Sci, Lab Thrombosis & Haemostasis, Ctr Appl Med Res, Pamplona 31008, Spain
[2] Univ Navarra, Prote Genom & Bioinformat Unit, Ctr Appl Med Res, Pamplona 31008, Spain
[3] Univ Navarra Clin, Dept Cardiol & Cardiovasc Surg, Pamplona, Spain
关键词
Animals models; endothelial cells; vascular remodelling; heart; gene expression; OXIDE SYNTHASE EXPRESSION; C-REACTIVE PROTEIN; RISK; THROMBOSIS; STROKE; CELLS; STATE;
D O I
10.1160/TH12-05-0285
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The leading cause of cardioembolic stroke is atrial fibrillation (AF), which predisposes to atrial thrombus formation. Although rheological alterations promote a hypercoagulable environment, as yet undefined factors contribute to thrombogenesis. The role of the endocardium has barely been explored. To approach this topic, rapid atrial pacing (RAP) was applied in four pigs to mimic AF. Left and right endocardial cells were isolated separately and their gene expression pattern was compared with that of four control pigs. The AF-characteristic rhythm disorders and endothelial nitric oxide synthase down-regulation were successfully reproduced, and validated RAP to mimic AF. A change was observed in the transcriptonnic endocardial profile after RAP: the expression of 364 genes was significantly altered (p < 0.01), 29 of them having passed the B > 0 criteria. The left atrial endocardium [325 genes (7 genes, B > 0)] was largely responsible for such alterations. Blood coagulation, blood vessel morphogenesis and inflammatory response are among the most significant altered functions, and help to explain the activation of coagulation observed after RAP: D-dimer, 0.49 (1.63) vs. 0.23 (0.24) mg/l [median (interquartile range)] in controls, p=0.02. Furthermore, three genes directly related to thrombotic processes were differentially expressed after RAP: FGL2 [fold change (FC)=0.85; p=0.007], APLP2 (FC=-0.47; p=0.005) and ADAMTS-18 (FC=-0.69; p=0.004). We demonstrate for the first time that AF induces a global expression change in the left atrial endocardium associated with an activation of blood coagulation. The nature of some of the altered functions and genes provides clues to identify new therapeutic targets.
引用
收藏
页码:742 / 749
页数:8
相关论文
共 50 条
  • [21] Left Atrial Strain and Incident Atrial Fibrillation in Older Adults
    Mannina, Carlo
    Ito, Kazato
    Jin, Zhezhen
    Yoshida, Yuriko
    Russo, Cesare
    Nakanishi, Koki
    Elkind, Mitchell S. V.
    Rundek, Tatjana
    Homma, Shunichi
    Di Tullio, Marco R.
    AMERICAN JOURNAL OF CARDIOLOGY, 2023, 206 : 161 - 167
  • [22] Left Atrial Appendage Closure for Stroke Prevention in Atrial Fibrillation
    Fender, Erin A.
    Kiani, Jawad G.
    Holmes, David R., Jr.
    CURRENT ATHEROSCLEROSIS REPORTS, 2016, 18 (11)
  • [23] Left Atrial Appendage Electrical Isolation as a Target in Atrial Fibrillation
    Nishimura, Marin
    Lupercio-Lopez, Florentino
    Hsu, Jonathan C.
    JACC-CLINICAL ELECTROPHYSIOLOGY, 2019, 5 (04) : 407 - 416
  • [24] Left Atrial Appendage Occlusion in Patients With Atrial Fibrillation and Cancer
    Shabtaie, Samuel A.
    Tan, Nicholas Y.
    Ward, Robert C.
    Lewis, Bradley R.
    Yang, Eric H.
    Holmes Jr, David R.
    Herrmann, Joerg
    JACC: CARDIOONCOLOGY, 2023, 5 (02): : 203 - 212
  • [25] Racial Differences in Atrial Fibrillation Prevalence and Left Atrial Size
    Marcus, Gregory M.
    Olgin, Jeffrey E.
    Whooley, Mary
    Vittinghoff, Eric
    Stone, Katie L.
    Mehra, Reena
    Hulley, Stephen B.
    Schiller, Nelson B.
    AMERICAN JOURNAL OF MEDICINE, 2010, 123 (04): : 375.e1 - 375.e7
  • [26] Left atrial appendage occlusion for atrial fibrillation and bleeding diathesis
    Kailey, Balrik Singh
    Koa-Wing, Michael
    Sutaria, Nilesh
    Mott, Tom
    Sohaib, Afzal
    Qureshi, Norman
    Shi, Christine
    Padam, Pritpal
    Howard, James
    Kanagaratnam, Prapa
    JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, 2023, 34 (12) : 2552 - 2562
  • [27] The Effect of Acute Onset Atrial Fibrillation on Left Atrial Thrombogenesis
    Lim, Han S.
    Willoughby, Scott R.
    Gan, Cheryl
    Schultz, Carlee
    Lau, Dennis H.
    Alasady, Muayad
    Leong, Darryl P.
    Abed, Hany
    Dimitri, Hany
    Roberts-Thomson, Kurt C.
    Worthley, Matthew I.
    Young, Glenn D.
    Sanders, Prashanthan
    CIRCULATION, 2010, 122 (21)
  • [28] Left Atrial Epicardial Adiposity and Atrial Fibrillation
    Batal, Omar
    Schoenhagen, Paul
    Shao, Mingyuan
    Ayyad, Ala Eddin
    Van Wagoner, David R.
    Halliburton, Sandra S.
    Tchou, Patrick J.
    Chung, Mina K.
    CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY, 2010, 3 (03): : 230 - 236
  • [29] Left atrial appendage exclusion in atrial fibrillation
    Rozen, Guy
    Margolis, Gilad
    Marai, Ibrahim
    Roguin, Ariel
    Rahamim, Eldad
    Planer, David
    Heist, Edwin Kevin
    Amir, Offer
    Tahiroglu, Ilgar
    Ruskin, Jeremy
    Mansour, Moussa
    Elbaz-Greener, Gabby
    FRONTIERS IN CARDIOVASCULAR MEDICINE, 2022, 9
  • [30] Left atrial function, inflammation, and prothrombotic response after radiofrequency ablation for atrial fibrillation
    Yin, Guangli
    Xie, Ruiqin
    You, Ling
    Yin, Hongning
    Sun, Yucui
    Wu, Jinglan
    Zhao, Yansha
    Geng, Xue
    Zhang, Yanan
    JOURNAL OF THE CHINESE MEDICAL ASSOCIATION, 2018, 81 (05) : 409 - 415