The Role of Inflammation in Cardiovascular Disease

Abstract

Atherosclerosis is a chronic inflammatory disease, in which the immune system has a prominent role in its development and progression. Inflammation-induced endothelial dysfunction results in an increased permeability to lipoproteins and their subendothelial accumulation, leukocyte recruitment, and platelets activation. Recruited monocytes differentiate into macrophages which develop pro- or anti-inflammatory properties according to their microenvironment. Atheroma progression or healing is determined by the balance between these functional phenotypes. Macrophages and smooth muscle cells secrete inflammatory cytokines including interleukins IL-1β, IL-12, and IL-6. Within the arterial wall, low-density lipoprotein cholesterol undergoes an oxidation. Additionally, triglyceride-rich lipoproteins and remnant lipoproteins exert pro-inflammatory effects. Macrophages catabolize the oxidized lipoproteins and coalesce into a lipid-rich necrotic core, encapsulated by a collagen fibrous cap, leading to the formation of fibro-atheroma. In the conditions of chronic inflammation, macrophages exert a catabolic effect on the fibrous cap, resulting in a thin-cap fibro-atheroma which makes the plaque vulnerable. However, their morphology may change over time, shifting from high-risk lesions to more stable calcified plaques. In addition to conventional cardiovascular risk factors, an exposure to acute and chronic psychological stress may increase the risk of cardiovascular disease through inflammation mediated by an increased sympathetic output which results in the release of inflammatory cytokines. Inflammation is also the link between ageing and cardiovascular disease through increased clones of leukocytes in peripheral blood. Anti-inflammatory interventions specifically blocking the cytokine pathways reduce the risk of myocardial infarction and stroke, although they increase the risk of infections.

A meta-analysis on inflammation and autonomic nervous system of coronary heart disease combined with depression

“…Inflammation is implicated in the pathological mechanism of cardiovascular disease. [36] In the process of atherosclerosis, pro-inflammatory factors, such as the tumor necrosis factor (TNF)-α, IL-1, IL-6, C-reactive protein (CRP) etc., induce endothelial dysfunction and promote the formation of lipid plaques. [37] CRP which is released from hepatocytes, reflects the acute phrase of inflammation response.…”

CRISPR screening in cardiovascular research

“…Many researchers have applied CRISPR screening in immune cells to investigate questions in tumor immunology (reviewed elsewhere) ( Li & Fei, 2020 ; Shi et al, 2022 ), but very few studies are linked to cardiovascular diseases. Inflammation plays a prominent role in the development of cardiovascular diseases such as atherosclerosis which involves inflammation-induced endothelial dysfunction and interplay between blood vessel cells and inflammation-related immune cells (e.g., monocytes and macrophages) ( Henein et al, 2022 ). Using immortalized murine macrophages and Nlrp3-dependent cell death as a readout, Schmid-Burgk et al described a genome-scale CRISPR screen, and pinpointed NEK7 as a critical player for NLRP3 inflammasome activation which underlies many metabolic diseases including atherosclerosis ( Schmid-Burgk et al, 2016 ).…”

Blood Count-Derived Inflammatory Markers and Acute Complications of Ischemic Heart Disease in Elderly Women

“…Atherosclerosis, the underlying cause of CVD, is a chronic disease with a prominent inflammatory component [ 19 ]. Taking this into account, the markers of subclinical systemic inflammation are of particular interest, especially those that incorporate different subtypes of immune cells.…”