7  Cardiovascular benefits of n-3 polyunsaturated fatty acids
N-3 PUFAs and many of the their endogenously generated metabolites act as bioactive lipid molecules with a wide array of properties against numerous disorders including CVD (Lordan, Redfern, Tsoupras, & Zabetakis, 2020; Lordan, Tsoupras, & Zabetakis, 2017; Moro, Nagahashi, Ramanathan, Takabe, & Wakai, 2016). Numerous studies have suggested higher consumption of n-3 PUFAs lowers the number of mortalities related to CVD (Darwesh, Sosnowski, Lee, Keshavarz-Bahaghighat, & Seubert, 2019; Kris-Etherton, Harris, Appel, & Nutrition, 2003; Lee, O'Keefe, Lavie, & Harris, 2009; Mozaffarian, 2007). For instance, Mozaffarian et al. demonstrated higher plasma levels of n-3 PUFA biomarkers in a U.S. adults cohort study was associated with lower total mortality attributable with fewer cardiovascular compared to non-cardiovascular deaths (Mozaffarian et al., 2013). Currently, the intake of n-3 PUFAs is still recommended by the American Heart Association to prevent clinical CVD episodes in individuals with predominant coronary heart disease, such as a recent MI, to reduce death rates as well as individuals with prevalent HF to reduce hospitalizations and number of mortalities (Sacks et al., 2017; Siscovick, et al., 2017).
The cardiovascular benefits of n-3 PUFAs could be attributed to their pleiotropic effects on the different elements of the cardiovascular system. Evidence suggests a higher intake of n-3 PUFAs has a beneficial effect on lipid profiles by replacing saturated fatty acids and lowering triglyceride levels, thereby stabilizing atherosclerotic plaques and reducing the incidence of thrombus formation (Plutzky, 1999; Thies et al., 2003). Furthermore, n-3 PUFAs can enrich cell membranes and alter the lipid raft structure and function leading to improved organelle and cellular function (Din et al., 2008), autonomic tone (Abuissa, O'Keefe Jr., Harris, & Lavie, 2005; O'Keefe Jr., Abuissa, Sastre, Steinhaus, & Harris, 2006), elevated arrhythmic thresholds (Anand, Alkadri, Lavie, & Milani, 2008) and ameliorating hypertension (Geleijnse, Giltay, Grobbee, Donders, & Kok, 2002; O'Keefe Jr. et al., 2006). Importantly, several experimental, clinical and epidemiological studies hypothesize that the cardioprotective effects of n-3 PUFAs and their metabolites are attributed mainly to their immunomodulatory properties. Notably, emerging evidence demonstrates the ability of n-3 PUFAs to reduce circulating levels of inflammatory chemokines, cytokines, and the pro-inflammatory metabolites derived from n-6 PUFAs (Calder, 2013, Calder, 2017).