Medial Injury/Dysfunction Induced Granulation Tissue Repair is the Pathogenesis of Atherosclerosis

TL;DR

This paper proposes that medial injury and dysfunctional repair processes, involving granulation tissue formation, are central to the development of atherosclerosis, offering a new perspective beyond classical hypotheses.

Contribution

It introduces a novel media dysfunction-based theory of atherosclerosis, emphasizing injury and repair mechanisms as key factors in disease pathogenesis.

Findings

Media injury leads to granulation tissue formation in arteries.

Media dysfunction causes vessel stiffening, aneurysm, or atherosclerosis.

Clinical features of atherosclerosis are explained by the proposed theory.

Abstract

Atherosclerosis, a chronic lesion of vascular wall, remains a leading cause of death and loss of life years. Classical hypotheses for atherosclerosis are long-standing mainly to explain atherogenesis. Unfortunately, these hypotheses may not explain the variation in the susceptibility to atherosclerosis. These issues are controversial over the past 150 years. Atherosclerosis from human coronary arteries was examined and triangle of media was found to be a true portraiture of cells injury in the media, and triangle of intima was a true portraiture of myofibroblast proliferation, extracellular matrix (ECM) secretion, collagen fiber formation and intimal thickening to repair media dysfunction. Myofibroblasts, ECM and lumen (intima)/vasa vasorum (VV) (adventitia) constitute granulation tissue repair. With granulation tissue hyperplasia, lots of collagen fibers (normal or denatured), foam cells and new capillaries formed. Thus, the following theory was postulated: Risk factors induce smooth muscle cells (SMCs) injury/loss, and fibrosis or structure destruction could be developed in the media, which lead to media dysfunction. Media dysfunction prompts disturbed mechanical properties of blood vessels, resulting in bigger pressure buildup in the intima and adventitia. Granulation tissues in the intima/adventitia develop to repair the injured media. Atherosclerosis, stiffening or aneurysm develops depending on media dysfunction severity and granulated tissue repair mode/degree. Nearly all characteristics of clinical atherosclerosis could be ideally interpreted with the theory. We believe that media dysfunction is a key initiator in the pathogenesis of atherosclerosis. It is expected that media dysfunction theory of atherosclerosis, should offer better understanding of the etiology for atherosclerosis.