  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.
