Structural, Pro-Inflammatory and Calcium Handling Remodeling Underlies Spontaneous Onset of Paroxysmal Atrial Fibrillation in JDP2-Overexpressing Mice

Abstract

Background: Cardiac-specific JDP2 overexpression provokes ventricular dysfunction and atrial dilatation in mice. We performed in vivo studies on JDP2-overexpressing mice to investigate the impact of JDP2 on the predisposition to spontaneous atrial fibrillation (AF). Methods: JDP2-overexpression was started by withdrawal of a doxycycline diet in 4-week-old mice. The spontaneous onset of AF was documented by ECG within 4 to 5 weeks of JDP2 overexpression. Gene expression was analyzed by real-time RT-PCR and Western blots. Results: In atrial tissue of JDP2 mice, besides the 3.6-fold increase of JDP2 mRNA, no changes could be detected within one week of JDP2 overexpression. Atrial dilatation and hypertrophy, combined with elongated cardiomyocytes and fibrosis, became evident after 5 weeks of JDP2 overexpression. Electrocardiogram (ECG) recordings revealed prolonged PQ-intervals and broadened P-waves and QRS-complexes, as well as AV-blocks and paroxysmal AF. Furthermore, reductions were found in the atrial mRNA and protein level of the calcium-handling proteins NCX, Cav1.2 and RyR2, as well as of connexin40 mRNA. mRNA of the hypertrophic marker gene ANP, pro-inflammatory MCP1, as well as markers of immune cell infiltration (CD68, CD20) were increased in JDP2 mice. Conclusion: JDP2 is an important regulator of atrial calcium and immune homeostasis and is involved in the development of atrial conduction defects and arrhythmogenic substrates preceding paroxysmal AF.

Integrative analysis and experiments to explore angiogenesis regulators correlated with poor prognosis, immune infiltration and cancer progression in lung adenocarcinoma

“…In a previous study, tumor angiogenesis was proven to have a positive correlation with many solid tumors, such as lung cancer, colorectal cancer, gastric cancer, and breast cancer [ 13 , 14 ]. Important predictive diagnostic and prognostic biomarkers of angiogenesis-related genes have been identified in some malignancies, including liver cancer, colorectal cancer, gastric cancer and urothelial cancer [ 15 – 17 ]. Thus, the correlation of the angiogenesis gene signature and clinical outcomes or clinical relevance needs to be elucidated in LUAD patients.…”

Transcriptome-wide high-throughput mapping of protein–RNA occupancy profiles using POP-seq

“…7 C). To further elaborate the sponge effect, we investigated a well-studied lncRNA MALAT1 which has been shown to interact with numerous RBPs 84 – 88 . As illustrated in Fig.…”

“…7 D, we observed that POP-seq captured peaks were sparsely distributed along the length of MALAT1 in contrast to the fairly uniform distribution of total RNA-seq reads showing higher expression of MALAT1 in K562 cells. We also included a track of ENCODE eCLIP peaks for RNA binding proteins HNRNPA1 and PTBP1 with known binding to MALAT1 84 shown in Fig. 7 D. The results suggest that HNRNPA1 and PTBP1 are most likely being sponged by highly expressed lncRNA MALAT1 in K562 cells.…”

Novel diagnostic criteria for atrial cardiomyopathy in patients with type 2 diabetes and atrial fibrillation

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