Targeting Early Atherosclerosis: A Focus on Oxidative Stress and Inflammation

Abstract

Atherosclerosis is a chronic vascular inflammatory disease associated to oxidative stress and endothelial dysfunction. Oxidation of low-density lipoprotein (LDL) cholesterol is one of the key factors for the development of atherosclerosis. Nonoxidized LDL have a low affinity for macrophages, so they are not themselves a risk factor. However, lowering LDL levels is a common clinical practice to reduce oxidation and the risk of major events in patients with cardiovascular diseases (CVD). Atherosclerosis starts with dysfunctional changes in the endothelium induced by disturbed shear stress which can lead to endothelial and platelet activation, adhesion of monocytes on the activated endothelium, and differentiation into proinflammatory macrophages, which increase the uptake of oxidized LDL (oxLDL) and turn into foam cells, exacerbating the inflammatory signalling. The atherosclerotic process is accelerated by a myriad of factors, such as the release of inflammatory chemokines and cytokines, the generation of reactive oxygen species (ROS), growth factors, and the proliferation of vascular smooth muscle cells. Inflammation and immunity are key factors for the development and complications of atherosclerosis, and therefore, the whole atherosclerotic process is a target for diagnosis and treatment. In this review, we focus on early stages of the disease and we address both biomarkers and therapeutic approaches currently available and under research.

Integrating Network Pharmacology and Component Analysis Study on Anti‐Atherosclerotic Mechanisms of Total Flavonoids of Engelhardia roxburghiana Leaves in Mice

“…Atherosclerosis involves the buildup of lipids and immune cells in the subendothelial space of arteries, and the development of immune and inflammatory response process . The contemporary approaches to atherosclerosis mainly include statins therapy, PCSK9 inhibitors, therapy targeting immunity and inflammation, antioxidant therapy .…”

“…According to the results of enrichment analysis, several inflammatory pathways such as NF‐ κ B signaling, Toll‐like receptor signaling, NOD‐like receptor signaling and TNF signaling pathway, which involved genes such as IL1B, PTGS2, TNF, VCAM1, IL6, CCL2, JUN, MAPK1, MAPK3, MAPK8, may be associated with atherosclerosis. As a key player of NF‐ κ B signaling, NF‐ κ B p65 subunit regulate various inflammatory cytokines release, such as ICAM‐1, TNF‐ α , IL‐6, IL‐1 β , VCAM‐1, eventually promoting inflammation responses in atherosclerosis . IL‐1 β is known to regulate adhesion molecules, such as VCAM‐1, and promote leukocyte adherence to endothelial cells and migration, which increase monocytes adhesion and infiltration into the vascular wall, leading to atherosclerosis .…”

“…As a key player of NF-κB signaling, NF-κB p65 subunit regulate various inflammatory cytokines release, such as ICAM-1, TNF-α, IL-6, IL-1β, VCAM-1, eventually promoting inflammation responses in atherosclerosis. [16] IL-1β is known to regulate adhesion molecules, such as VCAM-1, and promote leukocyte adherence to endothelial cells and migration, which increase monocytes adhesion and infiltration into the vascular wall, leading to atherosclerosis. [21,22] CCL2, known as monocyte chemoattractant protein-1 (MCP-1), plays essential roles in monocyte recruitment toward atherosclerotic arteries, and knock down of CCL2 may reduce atherosclerotic lesion size.…”

MiR155-5p Inhibits Cell Migration and Oxidative Stress in Vascular Smooth Muscle Cells of Spontaneously Hypertensive Rats

“…Chronic vascular oxidative stress and inflammation greatly contribute to the pathogeneses of hypertension and several vascular diseases [40][41][42]. It is known that ROS promote inflammation, and inflammation also enhances oxidative stress in cardiovascular diseases [43][44][45]. We found that the miR155-5p mimic attenuated oxidative stress and inflammation in VSMCs of SHR, as evidenced by reduced superoxide anion production, NAD(P)H oxidase activity, and expressions of NOX2, IL-1β, and TNF-α in VSMCs of SHR.…”

Novel Insight into Neuroimmune Regulatory Mechanisms and Biomarkers Linking Major Depression and Vascular Diseases: The Dilemma Continues

“…Atherosclerosis is a chronic vascular inflammatory disease associated with endothelial dysfunction accelerated by a myriad of factors [34]. In this context, several local pathogenic proatherosclerotic mechanisms were considered: increased expression of adhesion molecules; oxidation of low-density lipoprotein (LDL); expression of scavenger receptors promoting increased uptake of oxidized LDL; influx of foam cells; resistance to apoptosis; altered vasomotor tone; and increased production of macrophage chemoattractant protein, growth factors, and matrix metalloproteinases [35,36].…”