Role of aggregated medin in the pathogenesis of thoracic aortic aneurysm and dissection

Abstract

The pathogenesis of sporadic thoracic aortic aneurysm and dissection, which may lead to rupture of the aorta, remains largely unknown. Amyloid deposits, formed from the medin peptide, are very prevalent in the media of the thoracic aorta. We have studied the occurrence of medin-derived amyloid in specimens from patients with thoracic aortic aneurysm, aortic dissection type A and normal dimensioned aorta. Surprisingly, the amount of amyloid was significantly lower in the aneurysm and dissection groups (0.63±0.13 and 0.36±0.24 amyloid particles per mm 2 , respectively) compared to the control material (2.37 ± 0.58). However, focal medin immunoreactivity not associated with amyloid was found more conspicuously in the media of the two diseased groups. Recent amyloid research indicates that prefibrillar oligomeric aggregates, rather than mature amyloid fibrils, are toxic to the surrounding cells. The non-amyloid medin immunoreactivity observed may represent such toxic oligomers. This is supported by the fact that aggregated medin induced death of aortic smooth muscle cells in vitro. In addition, cells incubated together with medin increased the production of matrix metalloproteinase-2, a protease that degrades elastin and collagen and subsequently weakens the vessel wall. We therefore propose that medin oligomers are involved in the degeneration process of sporadic thoracic aortic aneurysm and dissection.

A rat model of aortic arch aneurysm with excellent survival

“…[17][18][19] Degeneration and a decrease in thickness of the vessel wall were reported to be the main characteristic histological changes in aortic aneurysm. 20 In contrast, our results showed hypertrophy in the vessel wall compared to the control group ( Figure 2). This result is not relevant to the natural history of aortic aneurysm, and this difference might be due to the duration of the study.…”

Milk Fat Globule Epidermal Growth Factor VIII Signaling in Arterial Wall Remodeling

“…It is well-known that PDGF-BB is not only a potent mitogen for VSMC, but also a key cellular chemoattractant in arterial restructuring [5], suggesting that MFG-E8 plays a crucial role in arterial remodeling. Indeed, MFG-E8 signaling is involved in both cardiovascular development and cardiovascular diseases (Table 1) [14, 15, 17–19, 23, 24, 26, 37, 43–52]. …”

Pathogenesis of Aortic Dissection: Elastic Fiber Abnormalities and Aortic Medial Weakness

“…Peng et al reported that the amount of medin-derived amyloid deposited in the aortic media was lower, and that of nonamyloid medin was higher, in aortic dissection patients than in a control group. 29) Medin amyloid is commonly found in the aortic media of individuals older than 50 years of age, and is a molecule in close contact with elastic fibers. Medin, an immature amyloid, has been suggested to be cytotoxic, and the possibility has been noted that medin may act on smooth muscle cells to increase the expression of matrix metalloproteinase (MMP)-2 in aortic dissection patients, thereby promoting the degradation of elastin and collagen.…”