Developing Pharmacological Therapies for Atrial Fibrillation Targeting Mitochondrial Dysfunction and Oxidative Stress: A Scoping Review

Figures

• 

  Figure 1. Pathophysiological mechanisms underlying the initiation and maintenance of atrial fibrillation (AF). Summary of upstream modulatory factors, underlying risk factors, and pathophysiological AF-associated mechanisms. Abbreviations: PITX2, paired-like homeodomain transcription factors 2; KCNN3 = Potassium Ca2+ctivated Channel; If = funny current; LTCC = L-type Ca2+ channel; RyR2 = ryanodine receptor 2; SERCA2a = SR− Ca2+ ATPase; cAMP, 3′,5′-cyclic adenosine monophosphate; PKA and PKG, protein kinase A and G; CaMKII = Ca2+-calmodulin dependent protein-kinase type-II; NO = nitric oxide; ROS = reactive oxygen species; NADPH =nicotinamide adenine dinucleotide phosphate; cGMP = cyclic guanosine monophosphate; AP = action potential; SR = sarcoplasmic reticulum; EADs/DADs = early/delayed afterdepolarizations; Cx40/43 = connexin 40/43; AF, atrial fibrillation. Source: [26].

• 

  Figure 2. Preferred Reporting ltems for Systematic Reviews and Meta-Analysis flowchart demonstrating the identification, screening, and studies included in this research.

• 

  Figure 3. Diagrams of oxidative stress production pathways. Source: [67].

• 

  Figure 4. Molecular mechanisms of SGLTi on redox signaling in cardiomyocytes. Source: [39].

• 

  Figure 5. Pharmacological interventions target the basic mechanisms of atrial fibrillation. Abbreviations: SGLT2, sodium-glucose cotransporter 2; DDP-4, dipeptidyl peptidase-4; TZDs, thiazolidinediones; TMZ, trimetazidine. Source: [27].

• 

  Figure 6. The mechanisms regulated by HSPs in atrial fibrillation. Intracellular HSP70s and HSP60 participate in autophagy, ER-stress, and oxidative stress reactions, exerting antioxidative and antiapoptotic effects and preventing atrial remodeling. However, when released into the extracellular matrix in a free state, HSP60 and HSP70 bind to TLRs on the surface of the membrane to induce inflammatory responses by activating the MyD88/NF-κB pathway. HSP, heat shock protein; UPR, unfolded protein response; GRP78, glucose-regulated protein 78; eIF2α, α-subunit of eukaryotic initiation factor 2; ATF4, activating transcription factors 4; CHOP, CCAAT/enhancer-binding protein homology protein; IP3R1, inositol 1,4,5-trisphosphate receptors; VDAC1, voltage-dependent anion channel-1; SOD, superoxide dismutase; AIF, apoptosis-inducing factor; eEF2, eukaryotic elongation factor 2, NF-κB, nuclear factor kappa B, TLR4, Toll-like receptors 4. Source: [62].