Misrepair mechanism in the development of atherosclerotic plaques

TL;DR

This paper proposes that atherosclerotic plaques develop through a Misrepair mechanism, where imperfect repairs lead to localized damage accumulation, causing plaques to grow self-accelerating and inhomogeneous in arterial walls.

Contribution

It introduces a novel Misrepair-based explanation for the focalized and self-accelerating growth of atherosclerotic plaques, linking repair defects to disease progression.

Findings

Plaque growth is self-accelerating and focalized.

Older plaques grow faster than younger ones.

Misrepair accumulation causes inhomogeneity in plaques.

Abstract

Atherosclerosis is a disease characterized by the development of atherosclerotic plaques (APs) in arterial endothelium. The APs in part of an arterial wall are inhomogeneous on size and on distribution. In order to understand this in-homogeneity, the pathology of APs is analyzed by Misrepair mechanism, a mechanism proposed in our Misrepair-accumulation aging theory. I. In general, development of an AP is a result of repair of injured endothelium. Because of infusion and deposition of lipids beneath endothelial cells, the repair has to be achieved by altered remodeling of local endothelium. Such a repair is a Misrepair. During repair, smooth muscular cells (SMCs) are clustered and collagen fibers are produced to the lesion of endothelium for reconstructing an anchoring structure for endothelial cells and for forming a barrier to isolate the lipids. II. Altered remodeling (Misrepair) makes the local part of endothelium have increased damage-sensitivity and reduced repair-efficiency. Thus, this part of endothelium will have increased risk for injuries, lipid-infusion, and Misrepairs. Focalized accumulation of Misrepairs and focalized deposition of lipids result in development of a plaque. III. By a viscous circle between lipid-infusion and endothelium-Misrepair, growing of an AP is self-accelerating. Namely, once an AP develops, it grows in an increasing rate with time and it does not stop growing. Within part of an arterial wall, older APs grow faster than younger ones. The oldest and the biggest AP is the most threatening one in narrowing local vessel lumen. Therefore, the self-accelerated growing of an AP is a fatal factor in atherosclerosis. In conclusion, development of APs is focalized and self-accelerating, because it is a result of accumulation of Misrepairs of endothelium.