The mechanism of electrical remodeling in atrial fibrillation and current research status of natural drugs and active ingredients inhibiting atrial electrical remodeling

Figures

• 

  Figure 1. Ion channels and electrophysiological alterations in myocardial cells related to atrial electrical remodeling. (a) The upregulation of CaMKII results in an increased INa, leading to sodium-dependent calcium overload. This condition, along with other contributing factors, culminates in a comprehensive calcium overload that triggers AF by inducing EAD. (b) The hyperphosphorylation of RyR2, mediated by CaMKII, causes an abnormal release of SRCa2+. This release, combined with an increased influx of Ca2+, results in an overload of calcium within the cell. Subsequently, this activates the NCX, which enhances the expulsion of calcium from the cell, leading to delayed DAD and sustaining AF. (c) Reductions in ICa,L and INa, along with increases in IK−ATP, IKs, IKur, IK1, and IK2p, contribute to the shortening of the APD and AERP, thus facilitating atrial electrical remodeling. By Figdraw (http://www.figdraw.com).

• 

  Figure 2. miRNA and atrial electrical remodeling. miRNA plays a crucial role in the regulation of gene expression and is involved in multiple regulatory processes of atrial electrical remodeling. By Figdraw (http://www.figdraw.com).

• 

  Figure 3. Inflammatory responses and atrial electrical remodeling. Inflammatory factors that are involved in affecting atrial electrical remodeling primarily include PDGF, Ang Ⅱ, NLRP3, TNF-α, IL, and CRP. Among them, IL-6 and Ang Ⅱ slow down atrial conduction speed by inhibiting Cx, triggering an imbalance in local myocardial electrical activity. Ang Ⅱ, NLRP3, and TNF-α induce DAD by upregulating NCX protein activity. PDGF-AB, TNF-α, and Ang Ⅱ can jointly mediate the shortening of the APD by acting on sodium, potassium, and calcium channel proteins. CRP can induce calcium overload by upregulating ICa,L. Various inflammatory responses collectively promote the onset and development of atrial fibrillation by affecting atrial electrical remodeling. By Figdraw (http://www.figdraw.com).

• 

  Figure 4. Oxidative stress and atrial electrical remodeling. Oxidative stress significantly impacts atrial electrical remodeling, primarily because of the overproduction of ROS. Critical in regulating this ROS generation are enzymes and factors such as XO, NOS, NOX, and FGF-21. By Figdraw (http://www.figdraw.com).

• 

  Figure 5. Autonomic nervous system remodeling and atrial electrical remodeling. The ANS is a crucial structure in the nervous system for regulating the electromechanical activities of the myocardium. It functions comprehensively by regulating the release of neurotransmitters such as Ach and EPI through the SN and VN, playing a vital role in regulating the ionic homeostasis of myocardial cells. By Figdraw (http://www.figdraw.com).

• 

  Figure 6. Myocardial fibrosis and atrial electrical remodeling. Myocardial electrical remodeling and myocardial structural remodeling influence and promote each other. Myocardial structural remodeling leads to the relaxation of intercellular connection and electrical block, promotes the formation of reentry, strengthens the damage of myocardial cells, and further aggravates myocardial structural remodeling. Ion channel change, miRNA expression, oxidative stress, inflammatory response, and autonomic nervous system remodeling are the common factors influencing myocardial electrical remodeling and myocardial structural remodeling. By Figdraw (http://www.figdraw.com).

• 

  Figure 7. The chemical structure of active components in natural medicines.

• 

  Figure 8. The mechanism of natural drugs and active components in treating atrial fibrillation through the regulation of atrial electrical remodeling. Natural drugs and their active ingredients primarily enhance myocardial electrical remodeling by regulating ion homeostasis, inflammatory responses, oxidative stress, and myocardial fibrosis mechanisms. With the rise of disciplines such as natural pharmacology and phytochemistry, clinicians and researchers have increasingly focused on the study and review of natural drugs and active ingredients. By Figdraw (http://www.figdraw.com).