A5048066616- Aortic Disease and Treatment Approaches
- Aortic aneurysm repair treatments
- Connective tissue disorders research
- Cardiac Valve Diseases and Treatments
- Cardiac Structural Anomalies and Repair
- Cardiovascular Issues in Pregnancy
- Congenital heart defects research
- Congenital Heart Disease Studies
- Cardiac Health and Mental Health
- RNA Research and Splicing
- Nuclear Structure and Function
- Cancer-related molecular mechanisms research
- Cerebrovascular and Carotid Artery Diseases
- Peptidase Inhibition and Analysis
- Genetic Associations and Epidemiology
- Family and Patient Care in Intensive Care Units
- DNA Repair Mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Cardiovascular Disease and Adiposity
- Protease and Inhibitor Mechanisms
- Infectious Aortic and Vascular Conditions
- Cardiovascular Function and Risk Factors
- Moyamoya disease diagnosis and treatment
- TGF-β signaling in diseases
- Protein Tyrosine Phosphatases
Broad Institute
2017-2025
Massachusetts General Hospital
2016-2025
Harvard University
2016-2025
Lemuel Shattuck Hospital
2024
University of Colorado Denver
2024
MaineGeneral Medical Center
2022
Mass General Brigham
2022
Johns Hopkins University
2010-2019
Johns Hopkins Medicine
2010-2019
Milwaukee Health Department
2018-2019
Transforming growth factor–β promotes aortic aneurysm formation through activation of its “noncanonical” signaling pathway.
Loeys-Dietz syndrome (LDS) is a connective tissue disorder that characterized by high risk for aneurysm and dissection throughout the arterial tree phenotypically resembles Marfan syndrome. LDS caused heterozygous missense mutations in either TGF-β receptor gene (TGFBR1 or TGFBR2), which are predicted to result diminished signaling; however, aortic surgical samples from patients show evidence of paradoxically increased signaling. We generated 2 knockin mouse strains with Tgfbr1 Tgfbr2...
The Loeys–Dietz syndrome (LDS) is a connective tissue disorder affecting the cardiovascular, skeletal, and ocular system. Most typically, LDS patients present with aortic aneurysms arterial tortuosity, hypertelorism, bifid/broad uvula or cleft palate. Initially, mutations in transforming growth factor-β (TGF-β) receptors (TGFBR1 TGFBR2) were described to cause LDS, hereby leading impaired TGF-β signaling. More recently, ligands, TGFB2 TGFB3, as well intracellular downstream effectors of...
Heart failure (HF) is a morbid and heritable disorder for which the biological mechanisms are incompletely understood. We therefore examined genetic associations with HF in large national biobank, assessed whether refined phenotypic classification would facilitate discovery.We defined all-cause among 488 010 participants from UK Biobank performed genome-wide association analysis. phenotype by classifying individuals left ventricular dysfunction without coronary artery disease as having...
Abstract Thoracic aortic aneurysm (TAA) has been associated with mutations affecting members of the TGF-β signaling pathway, or components and regulators vascular smooth muscle cell (VSMC) actomyosin cytoskeleton. Although both clinical groups present similar phenotypes, existence potential common mechanisms pathogenesis remain obscure. Here we show that VSMC cytoskeleton lead to formation a ternary complex comprising histone deacetylase HDAC9, chromatin-remodeling enzyme BRG1, long...
Background— Current practice guidelines recommend surgical repair of large thoracic aortic aneurysms to prevent fatal dissection or rupture, but limited natural history data exist support clinical criteria for timely intervention. Methods and Results— Of 3247 patients with aneurysm registered in our institutional Thoracic Aortic Center Database, we identified reviewed 257 nonsyndromic (age, 72.4±10.5 years; 143 female) descending thoracoabdominal without a whom intervention was not...
Calcium channel blockers (CCBs) are prescribed to patients with Marfan syndrome for prophylaxis against aortic aneurysm progression, despite limited evidence their efficacy and safety in the disorder. Unexpectedly, mice treated CCBs show accelerated expansion, rupture, premature lethality. This effect is both extracellular signal-regulated kinase (ERK1/2) dependent angiotensin-II type 1 receptor (AT1R) dependent. We have identified protein C beta (PKCβ) as a critical mediator of this pathway...
The aortic root is the predominant site for development of aneurysm caused by heterozygous loss-of-function mutations in positive effectors transforming growth factor-β (TGF-β) pathway. Using a mouse model Loeys-Dietz syndrome (LDS) that carries kinase-inactivating mutation TGF-β receptor I, we found effects this depend on lineage origin vascular smooth muscle cells (VSMCs). Secondary heart field–derived (SHF-derived), but not neighboring cardiac neural crest–derived (CNC-derived), VSMCs...
Background: Previous studies describing genetics evaluation in spontaneous coronary artery dissection (SCAD) have been retrospective nature or presented as single case reports. As part of a dedicated clinical program, we evaluated patients cardiovascular clinic to determine the role genetically triggered vascular disease and genetic testing SCAD. Methods Results: Patient data were entered prospectively into Massachusetts General Hospital SCAD registry database from July 2013 September 2017....
Marfan syndrome (MFS) is an autosomal dominant disorder of the connective tissue caused by mutations in