Genetic basis of aortic valvular disease

Koenig, Sara N.; Lincoln, Joy; Garg, Vidu

doi:10.1097/hco.0000000000000384

Cited by 23 publications

(10 citation statements)

References 51 publications

(59 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Specifically, mutations in NOTCH1 and GATA5 , have been associated with bicuspid aortic valve in humans. 21, 22 Consistent with findings in humans, dilation of the aorta has been reported in murine models with mutation of Notch1 , consistent with a role for Notch1 signaling in the development of the ascending aortic wall. 23, 24 Notch1 along with other genes are known to be important for the development of the aortic valve and ascending aorta, and it has been proposed that genetic abnormalities that result in BAV may also result in histopathologic changes, which predispose to aneurysm development.…”

Section: Discussionsupporting

confidence: 81%

Abnormal Longitudinal Growth of the Aorta in Children with Familial Bicuspid Aortic Valve

et al. 2017

Self Cite

View full text Add to dashboard Cite

Background Bicuspid aortic valve (BAV) is the most common type of congenital heart defect (CHD) and is associated with clinically significant cardiovascular complications including valve calcification and ascending aortopathy (AscAo), predominantly occurring in adulthood. While a limited number of genetic etiologies for BAV have been defined, family members of affected individuals display BAV along with other left-sided CHD. This has led to guidelines from the American Heart Association and American College of Cardiology that recommend echocardiographic screening of first-degree relatives of affected adults. While potentially beneficial in adults, the yield of such screening in children is unknown. The purpose of this study was to investigate a cohort of children with familial BAV to determine the frequency of development of AscAo, and to identify risk factors that contribute to abnormal aortic growth. Methods: Echocardiograms over a 10 year follow up period were reviewed on 26 patients with familial BAV (22 male, 4 female; 22 with isolated BAV, 6 with BAV and aortic coarctation (CoA)). All had a family history of CHD and were recruited from 2005–2010 as part of a genetics research study. Four aortic segments (annulus, root, sinotubular junction, ascending aorta) on parasternal long axis echocardiographic images were measured by a single observer. The mean age at first echocardiogram was 7.1+/−5.5 years and 13.8+/−6.2 years on the last. Only patients with >2 echocardiograms in the 10 year period were included. Z score measurements of the aorta were plotted over time and based on these the cohort was divided into two groups: Group 1 (abnormal) – Z score for any segment >2 or a change in Z score >2 over follow up; Group 2 (normal) – Z score <2 throughout follow up and change in Z score <2. Results 19 out of 26 children displayed abnormal aortic growth or dilation of the aorta. BAV with right/left cusp fusion was more frequent in Group 1(15/18) versus Group 2(3/7) (p<0.05). There were no significant differences in gender, aortic valve dysfunction, presence of CoA, family history, cardiac function, presence of left ventricular hypertrophy, or medication use between the 2 groups. Conclusions In our longitudinal study of children with familial BAV, the majority display evidence of abnormal growth of the ascending aorta during the follow up period consistent with AscAo and support the extension of current adult guidelines to the pediatric population. While we find that right/left cusp fusion is a risk factor for abnormal aortic growth, additional studies are needed to identify other factors to better select children who require serial screening.

show abstract

Section: Discussionsupporting

confidence: 81%

Abnormal Longitudinal Growth of the Aorta in Children with Familial Bicuspid Aortic Valve

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…Previous studies hypothesized that EndoMT may also play a role in the pathogenesis of BAV. Additionally, genes involved in this process such as NOTCH1, TGFBR2 , and SMAD6 , have been found to cause BAV in mouse models, as well as being linked to BAV in human studies (Garg et al, 2005 ; Girdauskas et al, 2011b ; Tan et al, 2012 ; Andelfinger et al, 2016 ; Gillis et al, 2017 ; Koenig et al, 2017 ). Mice with Notch1 missense alleles have been characterized with multiple outflow tract and EndoMT defects (Koenig et al, 2015 ).…”

Section: Notch1 Signaling In Taamentioning

confidence: 99%

Thoracic Aortic Aneurysm Development in Patients with Bicuspid Aortic Valve: What Is the Role of Endothelial Cells?

et al. 2017

View full text Add to dashboard Cite

Bicuspid aortic valve (BAV) is the most common type of congenital cardiac malformation. Patients with a BAV have a predisposition for the development of thoracic aortic aneurysm (TAA). This pathological aortic dilation may result in aortic rupture, which is fatal in most cases. The abnormal aortic morphology of TAAs results from a complex series of events that alter the cellular structure and extracellular matrix (ECM) composition of the aortic wall. Because the major degeneration is located in the media of the aorta, most studies aim to unravel impaired smooth muscle cell (SMC) function in BAV TAA. However, recent studies suggest that endothelial cells play a key role in both the initiation and progression of TAAs by influencing the medial layer. Aortic endothelial cells are activated in BAV mediated TAAs and have a substantial influence on ECM composition and SMC phenotype, by secreting several key growth factors and matrix modulating enzymes. In recent years there have been significant advances in the genetic and molecular understanding of endothelial cells in BAV associated TAAs. In this review, the involvement of the endothelial cells in BAV TAA pathogenesis is discussed. Endothelial cell functioning in vessel homeostasis, flow response and signaling will be highlighted to give an overview of the importance and the under investigated potential of endothelial cells in BAV-associated TAA.

show abstract

“…Combining pathological characterization of the leaflets following resection with network-based analysis of the proteomic and transcriptomic data has yielded new insight into the potential molecular drivers of aortic valve disease. Coupled with new genome wide association studies that have revealed new lipid associations with aortic valve disease, these big data approaches may provide new clues about points of non-invasive therapeutic intervention and the development of drug-based therapies (58, 59). However, challenges remain in identification of patients during the early stages of disease before gross remodeling of the aortic valve leaflets necessitate replacement.…”

Section: Valve Disease and Valve Repair And Replacement Technologiesmentioning

confidence: 99%

After 50 Years of Heart Transplants: What Does the Next 50 Years Hold for Cardiovascular Medicine? A Perspective From the International Society for Applied Cardiovascular Biology

Hutcheson

Goergen

Schoen

et al. 2019

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

The first successful heart transplant 50 years ago by Dr.Christiaan Barnard in Cape Town, South Africa revolutionized cardiovascular medicine and research. Following this procedure, numerous other advances have reduced many contributors to cardiovascular morbidity and mortality; yet, cardiovascular disease remains the leading cause of death globally. Various unmet needs in cardiovascular medicine affect developing and underserved communities, where access to state-of-the-art advances remain out of reach. Addressing the remaining challenges in cardiovascular medicine in both developed and developing nations will require collaborative efforts from basic science researchers, engineers, industry, and clinicians. In this perspective, we discuss the advancements made in cardiovascular medicine since Dr. Barnard's groundbreaking procedure and ongoing research efforts to address these medical issues. Particular focus is given to the mission of the International Society for Applied Cardiovascular Biology (ISACB), which was founded in Cape Town during the 20th celebration of the first heart transplant in order to promote collaborative and translational research in the field of cardiovascular medicine.

show abstract

Genetic basis of aortic valvular disease

Cited by 23 publications

References 51 publications

Abnormal Longitudinal Growth of the Aorta in Children with Familial Bicuspid Aortic Valve

Abnormal Longitudinal Growth of the Aorta in Children with Familial Bicuspid Aortic Valve

Thoracic Aortic Aneurysm Development in Patients with Bicuspid Aortic Valve: What Is the Role of Endothelial Cells?

After 50 Years of Heart Transplants: What Does the Next 50 Years Hold for Cardiovascular Medicine? A Perspective From the International Society for Applied Cardiovascular Biology

Contact Info

Product

Resources

About