A Novel Human Biospecimen Repository for Clinical and Molecular Investigation of Thoracic Aortopathy.

Courtney E. Vujakovich,Benjamin J. Landis

doi:10.3390/cardiogenetics11030017

Courtney E. Vujakovich, Benjamin J. Landis

Open Access

https://doi.org/10.3390/cardiogenetics11030017

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Abstract

Thoracic aortic aneurysm (TAA) is a heritable aortopathy with significant morbidity and mortality, affecting children and adults. Genetic causes, pathobiological mechanisms, and prognostic markers are incompletely understood. In 2015, the Collaborative Human Aortopathy Repository (CHAR) was created to address these fundamental gaps. Patients with thoracic aortopathy, associated genetic diagnoses, or aortic valve disease are eligible for prospective enrollment. Family members and controls are also enrolled. Detailed clinical and family data are collected, and blood and aortic tissue biospecimens are processed for broad usage. A total of 1047 participants were enrolled. The mean age in 834 affected participants was 47 ± 22 (range <1 to 88) years and 580 were male (70%). A total of 156 (19%) were under the age of 21 years. Connective tissue diagnoses such as Marfan syndrome were present in 123 (15%). Unaffected participants included relatives (N = 176) and healthy aorta tissue controls (N = 37). Aortic or aortic valve biospecimens were acquired from over 290 and 110 participants, respectively. RNA and protein were extracted from cultured aortic smooth muscle cells (SMCs) for 90 participants. Over 1000 aliquots of aortic SMCs were cryopreserved. The CHAR’s breadth, robust biospecimen processing, and phenotyping create a unique, multipronged resource to accelerate our understanding of human aortopathy.

Highlights

Thoracic aortic aneurysm (TAA) is an aortopathy that predisposes to aortic dissection, a life-threatening emergency
These included 834 affected individuals and 213 who were not affected. The latter group consisted of relatives enrolled for family-based investigation (N = 176) and participants whose aortic tissue samples were used as healthy control tissues (N = 37)
Consistent with epidemiological data showing that TAA is more common in males [12], there is a greater proportion of affected male participants than female

Summary

Introduction

Thoracic aortic aneurysm (TAA) is an aortopathy that predisposes to aortic dissection, a life-threatening emergency. There is a strong heritable basis for TAA [1]. Mendelian autosomal dominant connective tissue disorders including Marfan syndrome (MFS), Loeys–Dietz syndrome (LDS), and others have strong TAA associations. Autosomal dominant causes of familial TAA have been identified in patients without syndromic characteristics. Turner syndrome (TS) is a genomic disorder that is commonly associated with TAA, and copy number variants (microdeletions or microduplications) account for a proportion of TAA [2,3]. Bicuspid aortic valve (BAV) is the most common form of congenital heart disease and is frequently associated with TAA

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