Early Aberrant Angiogenesis Due to Elastic Fiber Fragmentation in Aortic Valve Disease.

Robert B Hinton,Robert P Mecham,Kevin E Bove,Benjamin J Landis,J Michael Smith,Amy M Opoka,Amy L Juraszek

doi:10.3390/jcdd8070075

Abstract

Elastic fiber fragmentation (EFF) is a hallmark of aortic valve disease (AVD), and neovascularization has been identified as a late finding related to inflammation. We sought to characterize the relationship between early EFF and aberrant angiogenesis. To examine disease progression, regional anatomy and pathology of aortic valve tissue were assessed using histochemistry, immunohistochemistry, and electron microscopy from early-onset (<40 yo) and late-onset (≥40 yo) non-syndromic AVD specimens. To assess the effects of EFF on early AVD processes, valve tissue from Williams and Marfan syndrome patients was also analyzed. Bicuspid aortic valve was more common in early-onset AVD, and cardiovascular comorbidities were more common in late-onset AVD. Early-onset AVD specimens demonstrated angiogenesis without inflammation or atherosclerosis. A distinct pattern of elastic fiber components surrounded early-onset AVD neovessels, including increased emilin-1 and decreased fibulin-5. Different types of EFF were present in Williams syndrome (WS) and Marfan syndrome (MFS) aortic valves; WS but not MFS aortic valves demonstrated angiogenesis. Aberrant angiogenesis occurs in early-onset AVD in the absence of inflammation, implicating EFF. Elucidation of underlying mechanisms may inform the development of new pharmacologic treatments.

Highlights

Aortic valve disease (AVD) obstructs outflow from the heart, affects 2.5% of the general population, and remains a significant cause of mortality [1,2]
Bicuspid aortic valve (BAV) was more common in earlyonset AVD, whereas cardiovascular comorbidities were more common in late-onset AVD
The findings of this study identify Elastic fiber fragmentation (EFF) and aberrant angiogenesis as early disease processes underlying AVD preceding the manifestation of inflammation (Figure 5)

Summary

Introduction

Aortic valve disease (AVD) obstructs outflow from the heart, affects 2.5% of the general population, and remains a significant cause of mortality [1,2]. The treatment for AVD continues to be primarily surgical, restricted to late-stage disease, and the number of replacement procedures increases rapidly with the aging population [3,4]. A central problem in the field remains the need to better understand early AVD processes and alternative medical treatment strategies [5]. AVD is characterized by cell and matrix abnormalities that are well established. Advances in human genetics and developmental biology have elucidated mechanisms that contribute to pathogenesis [6,7], but to date, early disease processes remain poorly understood, and no pharmacologic-based treatments that directly treat AVD have been established

Objectives

Methods

Results

Conclusion