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OBJECTIVE Mutations in the cardiac sodium channel gene SCN5A are responsible for type-3 long QT disease (LQT3). The genesis of cardiac arrhythmias in LQT3 is multifaceted, and the aim of this study was to further explore mechanisms by which SCN5A mutations lead to arrhythmogenesis in vivo. METHODS We engineered selective cardiac expression of a long QT(More)
Angiogenic factors are critical to the initiation of angiogenesis and maintenance of the vascular network. Here we use human genetics as an approach to identify an angiogenic factor, VG5Q, and further define two genetic defects of VG5Q in patients with the vascular disease Klippel-Trenaunay syndrome (KTS). One mutation is chromosomal translocation t(5;11),(More)
The Cardiac sodium channel gene SCN5A plays a critical role in cardiac electrophysiology and its mutations, either gain- or loss-of-functions, are associated with lethal arrhythmias. In this study, we investigated the effect of overexpression of SCN5A on the cardiac phenotype in a transgenic mouse model (TG-WT L10). Compared to NTG mice, heart rate, QRS(More)
MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression and play a critical role in development, homeostasis, and disease. Despite their demonstrated roles in age-associated pathologies, little is known about the role of miRNAs in human aging and longevity. We employed massively parallel sequencing technology to identify miRNAs expressed(More)
Only two genome-wide significant loci associated with longevity have been identified so far, probably because of insufficient sample sizes of centenarians, whose genomes may harbor genetic variants associated with health and longevity. Here we report a genome-wide association study (GWAS) of Han Chinese with a sample size 2.7 times the largest previously(More)
Increased cardiac angiotensin converting enzyme-1 (ACE1) is found in individuals who carry a deletion in intron 16 of ACE1 gene or in individuals who suffer from cardiac disorders, such as hypertrophy. However, whether a single increase in ACE1 expression leads to spontaneous cardiac defects remains unknown. To determine if the increased cardiac ACE1(More)
Numerous studies have revealed that Rap1 (Ras-proximate-1 or Ras-related protein 1), a small GTPase protein, plays a crucial role in mediating cAMP signaling in isolated cardiac tissues and cell lines. However, the involvement of Rap1 in the cardiac development in vivo is largely unknown. By injecting anti-sense morpholino oligonucleotides to knock down(More)
Excessive activation of the transforming growth factor beta signaling pathway and disorganized cellular skeleton caused by genetic mutations are known to be responsible for the inherited thoracic aortic aneurysms and dissections (TAAD), a life-threatening vascular disease. To investigate the genotype–phenotype correlation, we screened genetic mutations of(More)
Entry of calcium into cardiomyocyte via L-type calcium channel (LTCC) is fundamental to cardiac contraction. CACNA1C, a type of LTCC and a hallmark of a matured ventricular myocyte, is developmentally regulated. Here, we identified 138 potential transcription factors by a comparative genomic study on 5-kb promoter regions of CACNA1C gene across eight(More)
Coronary artery disease (CAD) is the leading cause of death and disability in the world. Genome-wide association studies have implicated the importance of the genetic contribution of vascular smooth muscle cells (VSMCs) function in CAD susceptibility. The aberrant phenotypic modulation of VSMC is responsible for the pathological vascular intima hyperplasia(More)