Novel Anti-Inflammatory Therapies in Coronary Artery Disease and Acute Coronary Syndromes

Abstract

Evidence suggests that inflammation plays an important role in atherosclerosis and the consequent clinical presentation, including stable coronary artery disease (CAD) and acute coronary syndromes (ACS). The most essential elements are cytokines, proteins with hormone-like properties that are produced by the immune cells, endothelial cells, platelets, fibroblasts, and some stromal cells. Interleukins (IL-1β and IL-6), chemokines, interferon-γ (IFN-γ), and tumor necrosis factor-alpha (TNF-α) are the cytokines commonly associated with endothelial dysfunction, vascular inflammation, and atherosclerosis. These molecules can be targeted by commonly used therapeutic substances or selective molecules that exert targeted anti-inflammatory actions. The most significant anti-inflammatory therapies are aspirin, statins, colchicine, IL-1β inhibitors, and IL-6 inhibitors, along with novel therapies such as TNF-α inhibitors and IL-1 receptor antagonists. Aspirin and statins are well-established therapies for atherosclerosis and CAD and their pleiotropic and anti-inflammatory actions contribute to their efficacy and favorable profile. Colchicine may also be considered in high-risk patients if recurrent ACS episodes occur when on optimal medical therapy according to the most recent guidelines. Recent randomized studies have also shown that therapies specifically targeting inflammatory interleukins and inflammation can reduce the risk for cardiovascular events, but these therapies are yet to be fully implemented in clinical practice. Preclinical research is also intense, targeting various inflammatory mediators that are believed to be implicated in CAD, namely repeated transfers of the soluble mutant of IFN-γ receptors, NLRP3 inflammasome inhibitors, IL-10 delivery by nanocarriers, chemokine modulatory treatments, and reacting oxygen species (ROS) targeting nanoparticles. Such approaches, although intriguing and promising, ought to be tested in clinical settings before safe conclusions can be drawn. Although the link between inflammation and atherosclerosis is significant, further studies are needed in order to elucidate this association and improve outcomes in patients with CAD.

Role of Lipid-Lowering and Anti-Inflammatory Therapies on Plaque Stabilization

“…Hypertension, diabetes, smoking, stress, and pollution may promote plaque formation [ 2 , 3 ]. The initial steps of atherogenesis include endothelial dysfunction and abnormal lipid metabolism, which are caused by inflammation.…”

“…Interleukin 6 is secreted by macrophages, monocytes, fibroblasts, and endothelial cells. It has both pro-inflammatory and pro-thrombotic properties [ 3 ]. It may promote both atherosclerosis and plaque vulnerability.…”

“…In vitro evidence suggests that this cytokine may act as a regulatory protein in the atherosclerotic process [ 89 ]. The role of inflammatory pathways in atherosclerosis was described in detail by Soehnlein et al and Dimitroglou et al [ 3 , 90 ].…”

Systemic impacts of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) on heart, muscle, and kidney related diseases

“…Among the key players, Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-6 (IL-6) are central to this process. TNF-α exacerbates endothelial dysfunction by inhibiting nitric oxide (NO) synthesis, a crucial regulator of vascular tone and endothelial health, and by inducing the expression of vascular cell adhesion molecules that promote leukocyte adherence and vascular inflammation ( Dimitroglou et al, 2023 ). IL-6, while possessing both pro- and anti-inflammatory properties, in the context of MASH tends to promote inflammation, contributing to vascular permeability and endothelial activation, thereby facilitating atherosclerosis ( Zegeye et al, 2018 ).…”

Crafting a Rigorous, Clinically Relevant Large Animal Model of Chronic Myocardial Ischemia: What Have We Learned in 20 Years?

“…Despite this substantial procedural volume, there are currently a large proportion of patients afflicted with CHD who lack revascularization options; this population has been estimated to reach as high as 1.8 million patients in North America alone [4]. The unparalleled breadth and the severity of the physiologic impact of heart disease constitute mandates to continue in the pursuit of improved and novel therapies [5][6][7][8][9][10][11][12][13][14]. The scientific community has responded robustly to this call, with the National Institutes of Health spending over USD 1 billion annually for the last 14 years on heart-disease-related research [15].…”