Annika Sundås Larsson

Lactadherin binds to elastin – a starting point for medin amyloid formation?

Medin amyloid is found in the medial layer of the aorta in almost 100% of the Caucasian population over 50 years of age. The medin fragment is 5.5 kDa and derives from the C2-like domain of the precursor protein lactadherin. We have previously reported immunohistochemical findings showing that medin amyloid co-localizes with elastic fibers of arteries and herein we show that lactadherin also is associated with elastic structures of human aortic material. In addition, results from in vitro binding assays demonstrate that both medin and lactadherin bind to tropoelastin in a concentration-dependent fashion, suggesting that the lactadherin-tropoelastin interaction is mediated via the medin domain. It is possible that lactadherin, which is a cell adhesion protein, in this way connects smooth muscle cells to the elastic fibers of arteries. Given that both medin and lactadherin interact with elastic fibers, elastin is probably an important component in the formation of medin amyloid.

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

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 mm2, 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.

Meristem Allocation as a Means of Assessing Reproductive Allocation

Publisher Summary The principle of resource allocation states that resources are not sufficient to fully supply the demands of all plant functions. If resources are limited, allocation to reproduction must decrease the allocation to some other plant functions. Allocation of resources to reproduction (reproductive allocation) has implications for several study fields in biology. Early studies discussed allocation patterns in light of the evolution of life-history traits and interaction between life-history traits and population dynamics. Initial studies considered animals, but the idea was soon applied to plant ecology to explain how allocation affects plant life-history strategies and plant community dynamics. To test the principle of allocation, biologists have tried to measure the resource use of different plant functions. This task has turned out to be difficult. It is not clear which currency should be used to measure reproductive allocation. Meristems have been proposed as a currency to measure reproductive allocation. Meristems come as distinct reproductive or vegetative entities. This chapter aims to discuss whether meristem allocation can be used as a supplement or a substitute when studying reproductive allocation. It first describes the structural, developmental, and physiological background of the meristem system. It then uses a modeling approach to show theoretically how meristem allocation may affect fitness. It discusses model assumptions and reviews empirical studies that have tested allocation models and their assumptions.

Signs of cross-seeding: aortic medin amyloid as a trigger for protein AA deposition

The highly diverse deposition pattern displayed by systemic amyloidoses, sometimes within the same amyloid disease, remains unexplained. The localized medin (AMed) amyloidosis develops from the precursor protein lactadherin and deposits in the media of the thoracic aorta in almost all individuals above 50 years of age. Given its high prevalence in the population, and the fact that systemic amyloidoses also deposit in the aorta, led us to investigate whether AMed amyloid could influence the tissue distribution of serum amyloid A derived (AA) amyloidosis. Seven aortas from patients with diagnosed systemic AA amyloidosis were investigated. Four displayed partial co-localization between medin and AA aggregates when examined with double-labeling immunofluorescence. Furthermore, in vitro studies showed that AMed amyloid-like fibrils promote the aggregation of protein AA into fibrils. The findings indicate that the highly frequent “senile” amyloidoses may have the potential to initiate fibril formation of the more uncommon amyloidoses by a cross-seeding mechanism.