Browsing by Author "Lin, Chieh-Yu"

Now showing 1 - 4 of 4
  • Thumbnail Image
    Item
    Apical Sparing Pattern of Longitudinal Strain and Positive Bone Scintigraphy in Metastatic Myocardial Calcification
    (Elsevier, 2020-04-22) Zhang, Kathleen W.; Sadhu, Justin S.; Miller, Brent W.; Brennan, Daniel C.; Bierhals, Andrew J.; Chen, Jie-Fu; Lin, Chieh-Yu; Vader, Justin M.; Medicine, School of Medicine
    An apical sparing pattern of longitudinal strain and positive radionuclide bone scintigraphy are believed to be specific for the diagnosis of transthyretin cardiac amyloidosis. We report on a young woman with apical sparing of longitudinal strain and positive bone scintigraphy who was found to have metastatic myocardial calcification at autopsy.
  • Thumbnail Image
    Item
    Epicardial calcineurin-NFAT signals through Smad2 to direct coronary smooth muscle cell and arterial wall development
    (Oxford University Press, 2014-01-01) Yang, Jin; Zeini, Miriam; Lin, Chieh-Yu; Chieh-Yu, Chien-Jung; Xiong, Yiqin; Shang, Ching; Han, Pei; Li, Wei; Quertermous, Thomas; Zhou, Bin; Chang, Ching-Pin; Department of Medicine, IU School of Medicine
    AIMS: Congenital coronary artery anomalies produce serious events that include syncope, arrhythmias, myocardial infarction, or sudden death. Studying the mechanism of coronary development will contribute to the understanding of the disease and help design new diagnostic or therapeutic strategies. Here, we characterized a new calcineurin-NFAT signalling which specifically functions in the epicardium to regulate the development of smooth muscle wall of the coronary arteries. METHODS AND RESULTS: Using tissue-specific gene deletion, we found that calcineurin-NFAT signals in the embryonic epicardium to direct coronary smooth muscle cell development. The smooth muscle wall of coronary arteries fails to mature in mice with epicardial deletion of calcineurin B1 (Cnb1), and accordingly these mutant mice develop cardiac dysfunction with reduced exercise capacity. Inhibition of calcineurin at various developmental windows shows that calcineurin-NFAT signals within a narrow time window at embryonic Day 12.5-13.5 to regulate coronary smooth muscle cell development. Within the epicardium, NFAT transcriptionally activates the expression of Smad2, whose gene product is critical for transducing transforming growth factor β (TGFβ)-Alk5 signalling to control coronary development. CONCLUSION: Our findings demonstrate new spatiotemporal and molecular actions of calcineurin-NFAT that dictate coronary arterial wall development and a new mechanism by which calcineurin-NFAT integrates with TGFβ signalling during embryonic development.
  • Thumbnail Image
    Item
    Inappropriate p53 Activation During Development Induces Features of CHARGE Syndrome
    (Nature Publishing Group, 2014-10-09) Van Nostrand, Jeanine L.; Brady, Colleen A.; Jung, Heiyoun; Fuentes, Daniel R.; Kozak, Margaret M.; Johnson, Thomas M.; Lin, Chieh-Yu; Lin, Chien-Jung; Swiderski, Donald L.; Vogel, Hannes; Bernstein, Jonathan A.; Attié-Bitach, Tania; Chang, Ching-Pin; Wysocka, Joanna; Martin, Donna M.; Attardi, Laura D.; Department of Medicine, IU School of Medicine
    CHARGE syndrome is a multiple anomaly disorder in which patients present with a variety of phenotypes, including ocular coloboma, heart defects, choanal atresia, retarded growth and development, genitourinary hypoplasia and ear abnormalities. Despite 70-90% of CHARGE syndrome cases resulting from mutations in the gene CHD7, which encodes an ATP-dependent chromatin remodeller, the pathways underlying the diverse phenotypes remain poorly understood. Surprisingly, our studies of a knock-in mutant mouse strain that expresses a stabilized and transcriptionally dead variant of the tumour-suppressor protein p53 (p53(25,26,53,54)), along with a wild-type allele of p53 (also known as Trp53), revealed late-gestational embryonic lethality associated with a host of phenotypes that are characteristic of CHARGE syndrome, including coloboma, inner and outer ear malformations, heart outflow tract defects and craniofacial defects. We found that the p53(25,26,53,54) mutant protein stabilized and hyperactivated wild-type p53, which then inappropriately induced its target genes and triggered cell-cycle arrest or apoptosis during development. Importantly, these phenotypes were only observed with a wild-type p53 allele, as p53(25,26,53,54)(/-) embryos were fully viable. Furthermore, we found that CHD7 can bind to the p53 promoter, thereby negatively regulating p53 expression, and that CHD7 loss in mouse neural crest cells or samples from patients with CHARGE syndrome results in p53 activation. Strikingly, we found that p53 heterozygosity partially rescued the phenotypes in Chd7-null mouse embryos, demonstrating that p53 contributes to the phenotypes that result from CHD7 loss. Thus, inappropriate p53 activation during development can promote CHARGE phenotypes, supporting the idea that p53 has a critical role in developmental syndromes and providing important insight into the mechanisms underlying CHARGE syndrome.
  • Thumbnail Image
    Item
    A long non-coding RNA protects the heart from pathological hypertrophy
    (Nature Publishing Group, 2014-10-02) Han, Pei; Li, Wei; Lin, Chiou-Hong; Yang, Jin; Shang, Ching; Nuernberg, Sylvia T.; Jin, Kevin Kai; Xu, Weihong; Lin, Chieh-Yu; Lin, Chien-Jung; Xiong, Yiqin; Chien, Huanchieh; Zhou, Bin; Ashley, Euan; Bernstein, Daniel; Chen, Peng-Sheng; Chen, Huei-sheng Vincent; Quertermous, Thomas; Chang, Ching-Pin; Department of Medicine, IU School of Medicine
    The role of long noncoding RNA (lncRNA) in adult hearts is unknown