The Novel Triad of Atherosclerosis, ACE2, and Dysbiosis: A literature Review

Atherosclerosis, a chronic inflammatory disease and the leading cause of myocardial infarction and stroke, is marked by lipid accumulation, arterial stiffening, and plaque formation initiated by endothelial dysfunction. Despite its well-understood pathogenesis, therapeutic outcomes remain variable, highlighting the need for a more comprehensive understanding of its underlying mechanisms. ACE2, a crucial component of the renin-angiotensin system (RAS), converts pro-inflammatory Angiotensin II (Ang II) into anti-inflammatory and vasodilatory Angiotensin (1-7). ACE2 also supports gut health, facilitating essential amino acid transportation and maintaining intestinal immunity. Inflammation and oxidative stress in atherosclerosis can downregulate ACE2 expression and activity, impairing its protective functions. Dysbiosis may contribute to atherosclerosis because of a compromised intestinal barrier and translocation of pro-inflammatory bacterial components into circulation, triggering systemic inflammation. It also alters lipid metabolism, promoting the production of trimethylamine N-oxide (TMAO), linked to increased cardiovascular risk, and a reduction in protective short-chain fatty acids (SCFAs). This proposed triad reveals critical feedback loops in Atherosclerosis-induced inflammation, ACE2 function, as well as gut dysbiosis that exacerbate atherosclerosis. Conversely, optimal ACE2 function can support a healthy gut microbiome, offering protection against atherosclerosis. Understanding this triad provides a more holistic understanding of atherosclerosis and explains the observed heterogeneity in disease progression. Traditional monotherapies often fail to capture this complexity. This triad elucidates integrative therapeutic approaches for ACE2 dysregulation and gut dysbiosis, aiming to treat atherosclerosis more effectively.