Figure 1.

Hypothesis of the pathogenesis of medial sclerosis, greatly simplified diagram

a) Medial sclerosis is the final common pathway of diverse conditions with distinct pathogenesis. As a consequence of mechanisms not yet fully understood, a pathogenetic cascade of medial calcification is triggered. In monogenic diseases, there is a defect in the metabolism of adenosine. Especially in diabetes mellitus, advanced glycation end products (AGEs) are thought to play a key role. In patients with chronic kidney disease, disturbances of electrolyte metabolism and electrolyte homeostasis in the medial layer of the arterial wall are of special importance. Damage to elastic fibers and biochemical changes in the extracellular matrix may occur, especially with advanced age. Activations of a number of molecular mechanisms, including transdifferentiation of vascular smooth muscle cells from a contractile to a secretory phenotype and disturbances in the balance between promoters and inhibitors, are thought to be involved in the calcification processes seen in all types of the disease. Common to all processes is the crystallization of hydroxyapatite.

b) Onset of medial calcification already occurs in younger individuals and the process of calcification increases with age. In some cases, severe, abnormal medial calcifications may develop even in otherwise healthy individuals. Non-age-related medial sclerosis is characterized by progressive destruction of the media. The effects of medial sclerosis on hemodynamics are an area of ongoing research.

Histology images by courtesy of Dr. Alexey Kamenskiy, University Nebraska, Omaha, U.S.A.