Research Progress on the Relationship between Atherosclerosis and Inflammation

Abstract

Atherosclerosis is a chronic inflammatory disease; unstable atherosclerotic plaque rupture, vascular stenosis, or occlusion caused by platelet aggregation and thrombosis lead to acute cardiovascular disease. Atherosclerosis-related inflammation is mediated by proinflammatory cytokines, inflammatory signaling pathways, bioactive lipids, and adhesion molecules. This review discusses the effects of inflammation and the systemic inflammatory signaling pathway on atherosclerosis, the role of related signaling pathways in inflammation, the formation of atherosclerosis plaques, and the prospects of treating atherosclerosis by inhibiting inflammation.

Phenolic Compounds Exerting Lipid-Regulatory, Anti-Inflammatory and Epigenetic Effects as Complementary Treatments in Cardiovascular Diseases

“…Under augmented oxidative stress, HDL becomes dysfunctional, presenting an increased number of MPO molecules that replace the PON1 molecules [17,19]. Thus, dysfunctional HDL can no longer protect LDL from oxidation, these alterations being the key risk factors for initiation and progression of the atherosclerotic plaques.Exposure of endothelial cells (EC) to risk factors induces their activation which consists in the production of pro-inflammatory molecules such as selectins (E-selectin, P-selectin, L-selectin), and of adhesion molecules, such as intracellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion 1 (VCAM-1) promoting monocyte adhesion and their transmigration into the sub-endothelium [20,21]. The macrophages produce pro-inflammatory cytokines, such as interleukin-1β (IL-1β), IL-12 and tumor necrosis factor-α (TNF-α), or chemokines, such as monocyte chemoattractant protein-1 (MCP-1) to attract more monocytes, thereby stimulating the inflammatory process [22].…”

“…A central role in the stimulation of the inflammatory stress in atherosclerosis is played by the nuclear factor kappa B Biomolecules 2020, 10, 641 3 of 41 (NF-κB) [23]. A strong inhibitor of NF-κB is sirtuin-1 (SIRT-1), and toll-like receptor 4 (TLR4) is an activator of NF-κB [21,24]. Another important pro-inflammatory intracellular protein complex is the nucleotide binding and domain-like receptor 3 (NLRP3) inflammasome, which stimulates the primary pro-inflammatory response determining the activation of the secondary inflammatory mediators, such as IL-6 or C reactive protein (CRP), thereby amplifying the inflammatory stress [25].Since the completion of the Human Genome Project, it has become evident that several additional mechanisms related to epigenomic, transcriptomic, epitranscriptomic, proteomic and metabolomic regulations are crucial for determinations of the phenotypes of many human disorders, including CVD [26].…”

Atherosclerosis as Pathogenetic Substrate for Sars-Cov2 &lsquo;&lsquo;Cytokine Storm&rsquo;&rsquo;<strong> </strong>

“…It is a chronic inflammatory disease characterized by infiltration, deposit and lipid oxidation which activates and promote a self-maintenance inflammatory state [22][23][24][25]. inflammasome pathway which results in proteolytic cleavage of proIL-1β and pro-IL18 to mature IL-1β and IL18 [26].…”

“…inflammasome pathway which results in proteolytic cleavage of proIL-1β and pro-IL18 to mature IL-1β and IL18 [26]. In the atherosclerosis disease, inflammatory signaling pathways activated are TLR4/NF-κβ and the JAK/STAT which contributed to boost inflammatory state raising cytokines expression and consequent activation of innate and adaptive immunity cells [24]. Therefore, immune system is dysregulated, due to chronic inflammation related to high plasmatic concentration of cholesterol, leading to pro-inflammatory pattern.…”

“…Increasingly studies have demonstrated the link between high levels of pro-inflammatory cytokines such as IL-6, TNF-α and IL-1β and progression and instability of atherosclerosis plaque pointing out their potential as novel target therapy [25,[29][30][31]. Clinical research is focusing on agents that inhibit IL-1, IL-6 and TNFα pathways in order to reduce risk of coronary heart disease and reduce adverse outcomes after injury [24,25,30].…”