Atherosclerosis and Inflammation: Insights from the Theory of General Pathological Processes

Abstract

Recent advances have greatly improved our understanding of the molecular mechanisms behind atherosclerosis pathogenesis. However, there is still a need to systematize this data from a general pathology perspective, particularly with regard to atherogenesis patterns in the context of both canonical and non-classical inflammation types. In this review, we analyze various typical phenomena and outcomes of cellular pro-inflammatory stress in atherosclerosis, as well as the role of endothelial dysfunction in local and systemic manifestations of low-grade inflammation. We also present the features of immune mechanisms in the development of productive inflammation in stable and unstable plaques, along with their similarities and differences compared to canonical inflammation. There are numerous factors that act as inducers of the inflammatory process in atherosclerosis, including vascular endothelium aging, metabolic dysfunctions, autoimmune, and in some cases, infectious damage factors. Life-critical complications of atherosclerosis, such as cardiogenic shock and severe strokes, are associated with the development of acute systemic hyperinflammation. Additionally, critical atherosclerotic ischemia of the lower extremities induces paracoagulation and the development of chronic systemic inflammation. Conversely, sepsis, other critical conditions, and severe systemic chronic diseases contribute to atherogenesis. In summary, atherosclerosis can be characterized as an independent form of inflammation, sharing similarities but also having fundamental differences from low-grade inflammation and various variants of canonical inflammation (classic vasculitis).

Effect of Ligustrazine on Lipopolysaccharide-induced Inflammatory Response of Vascular Endothelial Cells and its Possible Mechanism

“…AS is a multidimensional inflammatory disease characterized by complex molecular and cellular changes inside the artery wall (Blagov et al, 2023;Rubin et al, 2012;Sazonova et al, 2021). Inflammation is crucial in the onset, development, and pathophysiology of AS (Gusev & Sarapultsev, 2023;Wolf & Ley, 2019). As a result, HUVECs were used in this study due to their importance in vascular endothelial function.…”

Manno‐oligosaccharides from Cassia Seed Gum Attenuate Atherosclerosis through Inflammation Modulation and Intestinal Barrier Integrity Improvement in ApoE−/− Mice

“…Inulin has been demonstrated to decrease inflammation and plasma lipid levels, thereby inhibiting AS development. [19] Mannan oligosaccharides (MOS) are consisted of up to 10 mannose units linked via 𝛼- (1,6)or 𝛽- (1,4)bonds. They are produced from mannans present in the outer cell wall membranes of bacteria, plants, or yeast.…”

“…[ 3 ] The released cytokines and chemokines cause continuous inflammation, recruit inflammatory cells, and form atherosclerotic plaques, ultimately leading to the systemic activation of inflammatory pathways such as toll‐like receptors and the inflammasome. [ 4 ] Inflammatory signals affect permeability pathways and increase intestinal permeability, thus leading to the leakage of bacterial components into the circulatory system from the mesenteric veins and alteration of immune interactions in the gut. Increased levels of inflammatory factors act on target organs and tissues, ultimately leading to inflammation and disease.…”

Biomarkers in Systemic Sclerosis: An Overview

“…Skin thickness in SSc often spontaneously improves over time, confounding many interventional studies, as recently reported with belimumab and nintedanib [184][185][186][187][188][189][190][191][192]. However, mycophenolate, cyclophosphamide, and methotrexate have been shown to improve the mRss and reduce skin thickness in SSc [184][185][186][187][188][189][190][191][192]. Methotrexate has always been problematic in SSc as it can occasionally cause lung inflammation that can be confused with SSc-ILD [184][185][186][187][188][189][190][191][192].…”

“…However, mycophenolate, cyclophosphamide, and methotrexate have been shown to improve the mRss and reduce skin thickness in SSc [184][185][186][187][188][189][190][191][192]. Methotrexate has always been problematic in SSc as it can occasionally cause lung inflammation that can be confused with SSc-ILD [184][185][186][187][188][189][190][191][192]. Recently, tofacitinib, although not approved for SSc, has been shown to be more effective than methotrexate in reducing the mRss, ultrasound skin thickness, and musculoskeletal symptoms, and in reducing the biomarker genes regulated by the interferon in SSc [184][185][186][187][188][189][190][191][192].…”