Inflammation and cardiovascular disease: From mechanisms to therapeutics

Abstract

Inflammation constitutes a complex, highly conserved cascade of molecular and cellular events. Inflammation has been labeled as "the fire within," is highly regulated, and is critical to host defense and tissue repair. In general, inflammation is beneficial and has evolved to promote survival. However, inflammation can also be maladaptive when chronically activated and sustained, leading to progressive tissue injury and reduced survival. Examples of a maladaptive response include rheumatologic disease and atherosclerosis. Despite evidence gathered by Virchow over 100 years ago showing that inflammatory white cells play a role in atherogenesis, atherosclerosis was until recently viewed as a disease of passive cholesterol accumulation in the subendothelial space. This view has been supplanted by considerable basic scientific and clinical evidence demonstrating that every step of atherogenesis, from the development of endothelial cell dysfunction to foam cell formation, plaque formation and progression, and ultimately plaque rupture stemming from architectural instability, is driven by the cytokines, interleukins, and cellular constituents of the inflammatory response. Herein we provide an overview of the role of inflammation in atherosclerotic cardiovascular disease, discuss the predictive value of various biomarkers involved in inflammation, and summarize recent clinical trials that evaluated the capacity of various pharmacologic interventions to attenuate the intensity of inflammation and impact risk for acute cardiovascular events.

Keywords: Atherosclerosis; C-reactive protein; Cardiovascular disease; Cytokine; Inflammasome; Inflammation; Interleukin; Lipoprotein; Microbiome.

Fig. 1

Figure legend: inflammation plays a key role in all phases of atherosclerosis. Abbreviations: ICAM, Intercellular adhesion molecule; VCAM, Vascular cell adhesion molecule; IL, interleukin; MQ, macrophage; MMP, metalloproteinases; VSMC, vascular smooth muscle cell; Ox-LDL, oxidized low-density lipoprotein.

Fig. 2

Figure legend: Risk factors and mediators of inflammation. Abbreviations: AGEs, Advanced glycation end products; FA, free fatty acids; TNF-α, tumor necrosis factor-α; IL, interleukin; INF-γ, interferon-γ; MCP-1, monocyte chemoattractant protein-1; ROS, reactive oxygen species; SCFA, short-chain fatty acids; LPS, lipopolysaccharides; TMAO, trimethylamine N-oxide; Ox-LDL, oxidized low-density lipoprotein; HDL, high-density lipoprotein; ApoC III, apolipoprotein C III; Lp(a), lipoprotein (a).

Fig. 3

Figure legend: Therapies targeting inflammation for atherosclerotic cardiovascular disease prevention. Abbreviations: ASCVD, atherosclerotic cardiovascular disease; EPA, eicosapentaenoic acid.