Table 4.
Possible mechanisms underlying anti-arrhythmic effect of polyunsaturated fatty acids Ito: transient outward potassium current; Ik: delayed rectifier potassium current; PUFA Polyunsaturated Fatty Acids; SR: Sarcoplasmic Reticulum; TXA2: Thromboxane A2; AA: Arachidonic acid; HRV: Heart Rate Variability; NEFA: Non-esterified Fatty Acids; cGMP: cyclic guanosine monophosphate; TGFβ1: Transforming Growth Factor β1; Akt: protein kinase B; EGF: Epidermal Growth Factor.
| Effect | Mechanism | References |
|---|---|---|
| Reduced substrate vulnerability: | ||
| Altered myocyte electrophysiology | Modulation of ion channel (e.g. Na, K, L-type calcium) conductivity and currents (e.g. Ito, Ik, voltage-dependent sodium current) leading to reduced myocyte excitability. | [123,124,125,126,127] |
| Direct inhibition of SR calcium ion release channel/ryanodine receptor gating. | [128] | |
| Modulation of connexins. | [129,130] | |
| Changes in myocardial membrane phospholipids | Insertion of n3-PUFA into cell membranes alters protein function and signalling: e.g. anti-inflammatory; anti-thrombosis – reduced platelet aggregation and adhesion via reduced production of TXA2. Altered cardiac myocyte membrane phospholipid composition: reducing n6-PUFA while increasing n3-PUFA is antiarrhythmic by reducing calcium ion availability Lowering of pro-arrhythmic membrane NEFA concentration, preventing intracellular calcium overload. |
[117,118,119,120,121,122] |
| Altered balance of AA metabolites | Increased prostacyclin (anti-arrhythmic) to TXA2 (pro-arrhythmic) ratio. | [131,132] |
| Improved HRV | Calcium channel blocking effect on cardiac myocytes. | [133,134] |
| Modulation of sympathetic nervous system. | [135] | |
| Reduction of trigger events and remodelling | ||
| Reduced atherosclerosis | Decreased plaque inflammation and increased plaque stability; reduced neovascularisation. | [136,137,138] |
| Reduced thrombosis | Reduced platelet aggregation. | [136] |
| Reduced cardiac fibrosis | Increase cGMP levels which inhibit TGFβ1-induced cardiac fibrosis by blocking phosphorylation and nuclear translocation of Smad2/3 as well as inhibitory effects on some structural remodelling signalling molecules (e.g. Akt, EGF). | [139,140], |