What is the mechanism of atheromatous plaque formation?

From the Guidelines

Atherosclerotic plaque formation primarily occurs through a chronic inflammatory response in the arterial wall, as evidenced by the most recent and highest quality study 1. This process begins when the endothelium (inner lining of blood vessels) becomes damaged or dysfunctional, allowing LDL cholesterol to accumulate in the arterial wall. Inflammatory cells, particularly macrophages, are recruited to the site where they engulf the oxidized LDL and transform into foam cells. Over time, this persistent inflammation leads to the proliferation of smooth muscle cells, formation of a fibrous cap, and accumulation of lipids, creating the atherosclerotic plaque. While cholesterol accumulation, fibrous and muscle cell proliferation, and phagocytosis are all involved in plaque formation, they are components of the overarching chronic inflammatory process rather than the primary mechanism itself.

The key factors involved in the formation of atherosclerotic plaques include:

• Damage to the endothelium, allowing LDL cholesterol to accumulate
• Recruitment of inflammatory cells, such as macrophages, to the site of damage
• Transformation of macrophages into foam cells through the engulfing of oxidized LDL
• Proliferation of smooth muscle cells and formation of a fibrous cap
• Accumulation of lipids, leading to the creation of the atherosclerotic plaque

As noted in the study 1, inflammation plays a crucial role in the pathogenesis of atherosclerotic disease, with the formation of atherosclerotic plaques being a key component of this process. The study 1 also highlights the importance of early intervention in the treatment of atherosclerotic disease, given that the disease process begins in childhood and is progressive.

Overall, the mechanism of atheromatous plaque formation is complex and multifaceted, involving a range of cellular and molecular processes. However, at its core, the process is driven by a chronic inflammatory response in the arterial wall, as supported by the most recent and highest quality evidence 1.

From the Research

Mechanism of Atheromatous Plaque Formation

The formation of atheromatous plaques is a complex process involving multiple cellular and molecular mechanisms. Key factors contributing to plaque formation include:

• Systemic inflammation, which drives the inflammatory process and is a key driver of plaque formation and progression 2
• The accumulation of pro-inflammatory cytokines and the activation of transcription factors, creating a positive feedback loop that drives the creation and progression of atherosclerosis 3
• The role of arterial cells, including endothelial cells, smooth muscle cells, and fibroblasts, which can contribute to plaque formation or influence its composition 4
• Macrophage activation and function, which play a crucial role in the development and stability of atherosclerotic plaques 5

Cellular Processes Involved in Plaque Formation

The following cellular processes are involved in plaque formation:

• Infiltration of immune cells, such as monocytes/macrophages and T-lymphocytes, into the arterial wall 6
• Uptake of lipoproteins by immune cells, leading to the formation of lipid-laden foam cells 6
• Death of foam cells, resulting in the accumulation of dead cells, cellular debris, and extracellular cholesterol, forming a lipid-rich necrotic core 6
• Migration and proliferation of vascular smooth muscle cells into the intima layer, where they take up lipids and produce extracellular matrix proteins 6

Molecular Mechanisms Underlying Plaque Formation

The molecular mechanisms underlying plaque formation involve:

• The activation of inflammatory mediators and cytokines, such as IL-1β, IL-6, and TNF-α 2
• The upregulation of the nod-like receptor protein 3 (NLRP3) inflammasome and the Notch and Wnt pathways 3
• The increased expression of VEGF-A and the downregulation of connexins Cx32, Cx37, and Cx40, contributing to endothelial dysfunction and plaque formation 3
• The integration of macrophage intracellular signaling pathways and transcription factors, regulating plaque formation and stability 5