Junfeng Yan

Generation and Characterization of Vascular Smooth Muscle Cell Lines Derived from a Patient with a Bicuspid Aortic Valve

Thoracic aortic dilation is the most common malformation of the proximal aorta and is responsible for 1%–2% of all deaths in industrialized countries. In approximately 50% of patients with a bicuspid aortic valve (BAV), dilation of any or all segments of the aorta occurs. BAV patients with aortic dilation show an increased incidence of cultured vascular smooth muscle cell (VSMC) loss. In this study, VSMC, isolated from the ascending aorta of BAV, was treated with Simian virus 40 to generate a BAV-originated VSMC cell line. To exclude any genomic DNA or cross-contamination, highly polymorphic short tandem repeats of the cells were profiled. The cells were then characterized using flow cytometry and karyotyping. The WG-59 cell line created is the first reported VSMC cell line isolated from a BAV patient. Using an RT2 Profiler PCR Array, genes within the TGFβ/BMP family that are dependent on losartan treatment were identified. Endoglin was found to be among the regulated genes and was downregulated in WG-59 cells following treatment with different losartan concentrations, when compared to untreated WG-59 cells.

Imaging Mass Spectrometry for Characterization of Atrial Fibrillation Subtypes

Atrial fibrillation (AF) is a cardiac arrhythmia characterized by a rapid and irregular heart rhythm. AF types, paroxysmal (PX), persistent (PE), and long‐lasting persistent (LSP), require differences in clinical management. Unfortunately, a significant proportion of AF patients are clinically misclassified. Therefore, the aim of this study is to prove that MALDI‐Imaging (IMS) is valuable as a diagnostic aid in AF subtypes’ assessment.

Collagen analysis of the ascending aortic dilatation associated with bicuspid aortic valve disease compared with tricuspid aortic valve

Abstract Dilatation of the ascending aorta is a common occurrence in patients with bicuspid aortic valve (BAV). The aim of the current study was to characterize collagen content in advanced glycation end products (AGEs) of dilated aortic tissue from two distinct areas, concave and convex aortic sites in patients with BAV and TAV. Collagen contents extracted from 100 mg tissue was isolated by enzymatic digestion using pepsin and the nondigested material was further digested using cyanogen bromide, insoluble collagen fraction (ICF) was extracted by hydrochloric acid hydrolysis. BAV tissue showed diminished fluorescence of the pepsin extracted fraction (PEF) compared with TAV tissue (12.4 ± 1.0% vs 32.9 ± 7.6%, p = 0.05). Patients with BAV had PEF of collagens significantly diminished in the dilated ascending aorta, especially in its convex portion, in course of aging and increment of dilated diameters. It is suggestible that BAV patients present more highly AGE-modified collagens in their ascending aorta.

MicroRNA 208 in Atrial Fibrillation

MicroRNAs (miRNAs) are critical regulators of most major cellular processes and seem to play a vital role in the pathogenesis of numerous diseases including atrial fibrillation, the most commonly encountered cardiac rhythm disorder. Among the several miRNAs that appear to be involved in pathogenesis of atrial fibrillation, miRNA 208a is linked to fibrosis and proper cardiac conduction. We quantified the expression levels of miRNA 208a in left atrial appendage tissue of patients with paroxysmal (n=2), persistent (n=10), and long-standing persistent (n=7) arrhythmia using quantitative PCR. In paroxysmal atrial fibrillation, miRNA 208a was expressed moderately, whereas the expression was enhanced in persistent atrial fibrillation and significantly reduced in long-standing persistent atrial fibrillation. The difference between persistent and long-standing persistent atrial fibrillation was significant at p=0.02. The findings from our study suggest a decline in miRNA 208a expression with ongoing arrhythmia, possibly preceded by a rise in expression from paroxysmal to persistent atrial fibrillation or even long-standing persistent. The significant changes in miRNA 208a expression over the course of the disease may be used as an additional diagnostic tool to monitor the progression of atrial fibrillation.

Detection and Determination of Protein Network Associated with Atrial Fibrillation Phenotypes

Atrial fibrillation (AF) is associated with increased risks of stroke, cardiac failure, and mortality. Since the discrimination of AF phenotype is inadequate, accurate diagnosis remains elusive. Left atrial appendage tissue resected routinely during the maze procedure was collected from patients with paroxysmal, persistent, and longstanding persistent arrhythmia. In situ comprehensive proteomic approaches of matrix-assisted laser desorption/ ionization imaging mass spectrometry was used to differentiate and classify the spatial molecular processes in the pathology of AF phenotypes. Using unsupervised computational evaluation strategy, probabilistic latent semantic clustering, and receiver operating characteristic analysis (SCiLS Lab), the acquired peptide signatures and characteristic m/z species could be used to assign the AF phenotype. Intensity distribution of the given m/z values, which are discriminative for the considered cluster, was determined to distinguish between paroxysmal and persistent AF (mean, 4.08 ± 1.21 vs 1.59 ± 0.12, p=0.09) and persistent and long-standing persistent AF (1.59 ± 0.12 vs 6.85 ± 3.02, p=0.02). Tissue-based proteomic approach provides clinically relevant information, which may be beneficial in improving risk stratification in AF patients.