Posts Tagged: anti-arrhythmia agents

Translational Challenges in Atrial Fibrillation

Translational Challenges in Atrial Fibrillation

Jordi Heijman, Jean-Baptiste Guichard, Dobromir Dobrev, Stanley Nattel

Photoacoustic imaging to define patient-specific atrial fibrillation mechanisms. Photoacoustic imaging uses (1) a pulsed-wave laser beam to activate endogenous (eg, water molecules, lipids, collagen) or exogenous photoabsorbing molecules, producing (2) thermal vibrations that generate (3) acoustic waves, which can be detected and localized using (4) ultrasound. Integration of photoacoustic imaging in an electrophysiology catheter in combination with intracardiac echocardiography could be used to assess ablation lesions (through endogenous chromophores) and perform in vivo Ca2+ imaging through novel cell-permeable photoacoustic Ca2+ indicators. [Powerpoint File]

Translational Challenges in Atrial Fibrillation

Translational Challenges in Atrial Fibrillation

Jordi Heijman, Jean-Baptiste Guichard, Dobromir Dobrev, Stanley Nattel

Molecular targets for atrial fibrillation (AF) therapy. Extensive work during the past 20 years has identified several molecular mechanisms in atrial cardiomyocytes and fibroblasts contributing to AF-promoting electric and structural atrial remodeling, which are potential molecular targets for AF therapy. Notable targets include ion channels involved in atrial electrophysiology (blue box), atrial Ca2+-handling and Ca2+-signaling (red box), microRNAs (miRs) inhibiting protein translation or promoting mRNA degradation (green boxes) of several targets (indicated in bold), transcription factors and gene regulatory networks (purple box), the components of the myofilaments (teal box), oxidative stress and altered metabolism (pink box), and inflammation (orange box). For all these components, there is a strong focus on targets with atrial-selective or atrial-predominant expression or atrial-selective effects (indicated with *). AMPK indicates 5′ adenosine monophosphate-activated protein kinase; Ang-II, angiotensin-II; Ang-IIR, angiotensin-II receptor; CaMKII, Ca2+/calmodulin-depenent protein kinase-II; CaN, calcineurin; CTFGR, connective tissue growth factor receptor; Cx-43, connexin-43; Dsp, desmoplakin; ERK, extracellular signal-regulated protein kinases; HDAC, histone deacetylases; ICa,L, L-type Ca2+ current; IK1, basal inward-rectifier K+ current; IK2P, 2 pore-domain K+ current; IK,ACh, acetylcholine-activated inward-rectifier K+ current; IKr, rapid delayed-rectifier K+ current; IKs, slow delayed-rectifier K+ current; IKur, ultrarapid delayed-rectifier K+ current; IL-1β, interleukin-1β; IL1R, interleukin-1 receptor; INa, Na+ current; INaK, Na+-K+-ATPase current; INCX, Na+/Ca2+-exchange current; ISK, small-conductance Ca2+-activated K+ current; Ito, transient-outward K+ current; JAK/STAT, Janus kinase/signal transducers and activators of transcription; MAPK, mitogen-activated protein kinase; MEF2, myocyte enhancer factor-2; Mito, mitochondrion; MyBP-C, myosin-binding protein-C; MYL4, atrial light chain-1; NFAT, nuclear factor of activated T-cells; NLRP3, NACHT, LRR, and PYD domain binding protein-3; nNOS, neuronal nitric oxide synthase; PDGFR, platelet-derived growth factor receptor; PITX2, paired like homeodomain-2; PKC, protein kinase C; PLB, phospholamban; RLC, myosin regulatory light chain; ROS, reactive oxygen species; RyR2, ryanodine receptor channel type-2; SERCA2a, sarcoplasmic reticulum Ca2+-ATPase type-2a; SIRT1, sirtuin-1; SLN, sarcolipin; SR, sarcoplasmic reticulum; TBX5, T-box transcription factor-5; TGF-β1, transforming growth factor-β1; TGFβR, transforming growth factor-β receptor; TnC/TnI/TnT, troponin C/I/T; and TRPC3/TRPM7, transient receptor potential channel C3/M7. [Powerpoint File]