Person:
Isselbacher, Eric

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Isselbacher

First Name

Eric

Name

Isselbacher, Eric

Filters

2016 - 20182

Settings

Author's Publications: search.filters.isAuthorOfPublication.c3e7d640-bcfb-4ca0-b72f-ebabeb6ca92f

Search Results

Now showing 1 - 2 of 2
  • Thumbnail Image
    Publication
    Association between bicuspid aortic valve morphotype and regional dilatation of the aortic root and trunk
    (Springer Nature, 2016) Habchi, Karam M.; undefined, undefined; Ashikhmina, Elena; Vieira, Vanessa Montiero; Shahram, Jasmin T.; Isselbacher, Eric; Sundt, Thoralf; Shekar, Prem; Muehlschlegel, Jochen; Body, Simon
    Thoracic aortic disease, including thoracic aor- tic aneurysm (TAA), is frequently seen in patients with bicuspid aortic valve (BAV). We hypothesized that BAV morphotype would be associated with aortic aneurysm phe- notypes but that other patient variables would signiicantly modify this relationship. 829 patients between 18 and 90 years with BAV and available raw imaging of the aortic valve and the ascending aorta to its mid-portion prior to aortic valve and aortic surgery were examined. The sinuses of Valsalva and proximal ascending aorta were measured from 2-dimensional co-planar echocardiographic images. We observed strong associations between patient habitus and raw and normalized dimensions of the aortic root and ascending aorta. Patients with R–L morphotype presented at an older age with larger aortic root but similar ascend- ing aortic dimensions. After accounting for patient mor- phometric characteristics and severity of aortic valve dis- ease, patients with R–L valve morphotype were marginally more likely to have an aortic root aneurysm (86% vs. 78%; P=0.043), deined as aortic root dimension Z score ≥3 We observed only small diferences in aortic dimensions between BAV morphotypes, that are eclipsed by variation in patient habitus. We interpret these indings to mean that BAV patients will not likely beneit from therapies based on aortic valve morphotype. Rather, we propose that all BAV patients should undergo longitudinal follow-up, inde- pendent of valve morphotype. Guidelines for aortic surgery based upon dimensions alone may be improved by con- sidering patient characteristics such as age, body size and other characteristics.
  • Thumbnail Image
    Publication
    An HDAC9-MALAT1-BRG1 complex mediates smooth muscle dysfunction in thoracic aortic aneurysm
    (Nature Publishing Group UK, 2018) Lino Cardenas, Christian; Kessinger, Chase; Cheng, Yisha; MacDonald, Carolyn; MacGillivray, Thomas; Ghoshhajra, Brian; Huleihel, Luai; Nuri, Saifar; Yeri, Ashish; Jaffer, Farouc; Kaminski, Naftali; Ellinor, Patrick; Weintraub, Neal L.; Malhotra, Rajeev; Isselbacher, Eric; Lindsay, Mark
    Thoracic aortic aneurysm (TAA) has been associated with mutations affecting members of the TGF-β signaling pathway, or components and regulators of the vascular smooth muscle cell (VSMC) actomyosin cytoskeleton. Although both clinical groups present similar phenotypes, the existence of potential common mechanisms of pathogenesis remain obscure. Here we show that mutations affecting TGF-β signaling and VSMC cytoskeleton both lead to the formation of a ternary complex comprising the histone deacetylase HDAC9, the chromatin-remodeling enzyme BRG1, and the long noncoding RNA MALAT1. The HDAC9–MALAT1–BRG1 complex binds chromatin and represses contractile protein gene expression in association with gain of histone H3-lysine 27 trimethylation modifications. Disruption of Malat1 or Hdac9 restores contractile protein expression, improves aortic mural architecture, and inhibits experimental aneurysm growth. Thus, we highlight a shared epigenetic pathway responsible for VSMC dysfunction in both forms of TAA, with potential therapeutic implication for other known HDAC9-associated vascular diseases.