Apoptotic cell death, elastin loss, and elastic fiber fragmentation are involved in the pathogenesis of medial calcification in the human aorta

Abstract

Background: Vascular calcification, especially medial calcification, is associated with an increased risk of cardiovascular events and mortality. Although some mechanisms such as oxidative stress, apoptotic cell death, and trans-differentiation of vascular smooth muscle cells to osteogenic cells have been recognized, human aortic calcification mechanisms have not been researched extensively in the past. Thus, we employed histopathological analysis of human aortic samples to elaborate the pathological findings of medial calcification.

Patients and Methods: Human aortic samples surgically resected from six patients with aortic aneurysms were immunostained. The staining intensity of each field of view was quantified according to standard scoring criteria, and the scores were compared between normal, calcified, and transitional areas of human aortic tissue sections.

Results: In normal areas of human aortic tissue sections, the elastic fibers show an orderly arrangement and elastin is highly expressed, while in calcified areas the elastic fibers are ruptured and have a disordered arrangement with markedly reduced elastin expression compared to normal and transitional areas. Significant levels of apoptotic cell death were observed in the calcified and transitional areas, although alkaline phosphatase and osteocalcin expression were not detectable.

Conclusion: Apoptotic cell death, elastin loss, and elastic fiber fragmentation may be involved in the pathogenesis of medial calcification in human aortic aneurysms.