Anomalous origin of the left coronary artery from the pulmonary artery as a rare cause of mitral valve prolapse: a case report.

BACKGROUND: Mitral valve prolapse (MVP) is an etiologically heterogeneous disorder. Early diagnosis and prompt treatment of the underlying disease are of great significance. Herein, we present a rare case of MVP caused by anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). CASE PRESENTATION: A 22-year-old female presented with a 16-year history of anterior mitral leaflet prolapse. However, she had never experienced any discomfort before. At a routine follow-up, a transthoracic echocardiogram showed anterior mitral leaflet prolapse (A2) with moderate mitral regurgitation, and a retrograde blood flow from an extremely dilated left coronary artery (LCA). Further coronary angiography and coronary computed tomography angiography confirmed the diagnosis of ALCAPA. She subsequently underwent successful LCA reimplantation and concomitant mitral valve replacement. Intraoperatively, her mitral annulus was mildly dilated, anterior mitral valve leaflet appeared markedly thickened with rolled edges, and a chordae tendineae connecting the anterior leaflet (A2) was ruptured and markedly shortened. CONCLUSIONS: ALCAPA is a rare and potentially life-threatening congenital coronary artery anomaly that may cause mitral valve prolapse. Echocardiogram is an important screening tool for this disorder.

Resveratrol protects H9c2 cells against hypoxia-induced apoptosis through miR-30d-5p/SIRT1/NF-κB axis.

Previous studies have demonstrated the cardioprotective role of resveratrol (Res). However, the underlying molecular mechanisms involved in the protective role of Res are still largely unknown. H9c2 cells were distributed into five groups: normal condition (Control), DMSO, 20 mMRes (dissolved with DMSO), hypoxia (Hyp), and Res+Hyp. Cell apoptosis was evaluated using flow cytometry and protein analysis of cleaved caspase 3 (cle-caspase 3). qRT-PCR assay was performed to measure the expression of microRNA-30d-5p (miR-30d-5p). MTT assay was performed to evaluate the cell proliferation. The relationship between miR-30d- 5p and silent information regulator 1 (SIRT1) was confirmed by luciferase reporter, RNA immunoprecipitation (RIP), and western blot assays. Western blot was performed to analyze NF-κB/p65 and I-κBα expressions. Our data showed that hypoxia enhanced apoptosis and NF-κB signaling pathway, which was alleviated by Res treatment. Hypoxia increased the expression of miR-30d-5p while decreased the SIRT1expression, which was also attenuated by Res treatment. Furthermore, miR-30d-5p depletion inhibited the proliferation, reduced apoptosis and decreased the expression of cle-caspase 3 in H9c2 cells with hypoxia treatment. Luciferase reporter, RIP, and western blot assays further confirmed that miR-30d-5p negatively regulated the expression of SIRT1. Interestingly, the rescue-of-function experiments further indicated that knockdown of SIRT1 attenuated the effect of miR-30d-5p depletion on proliferation, apoptosis NF-κB signaling pathway inH9c2 cells with hypoxia treatment. In addition, the suppression of NF-κB signaling pathway increased cell viability while decreased cell apoptosis in hypoxia-mediatedH9c2 cells. Our data suggested Res mayprotectH9c2 cells against hypoxia-induced apoptosis through miR-30d-5p/SIRT1/NF-κB axis.

Effect of chronic intermittent hypobaric hypoxia on heart rate variability in conscious rats.

To examine the effect of chronic intermittent hypobaric hypoxia (CIHH) on heart rate variability (HRV), male adult Sprague Dawley rats were exposed to hypoxia (oxygen 11.1%) in a hypobaric chamber for 42 days, 6 hours each day, simulating an altitude of 5000 m. The body weight and blood pressure of rats were recorded once a week, electrocardiograms were analyzed continuously using biotelemetry, before, during and after CIHH treatment each day, and HRV was evaluated using spectrum analysis. No significant difference of body weight and blood pressure was found between CIHH and control rats. After 4 weeks of CIHH treatment, total power (TP) and very low-frequency component (VLF) were lower in CIHH rats than in control rats under hypobaric hypoxia condition. During CIHH treatment, low frequency (LF) was higher in 1 week and lower in 5-6 weeks in CIHH rats than control rats under hypobaric hypoxia, but not normoxic conditions. The high-frequency component (HF) was not changed during CIHH treatment, so LF/HF increased initially, and then recovered under the hypobaric hypoxia condition following 3 weeks of CIHH treatment. In addition, the HR was increased in CIHH rats after 4 weeks of CIHH treatment compared with control rats. Furthermore, HRV was altered significantly in control rats, but not in CIHH rats exposed to acute normobaric hypoxia. These data suggest that CIHH treatment modulates cardiac autonomic activity adaptively and inhibits the acute normobaric hypoxia-induced changes in HRV.

Hyperpolarization-Activated Cyclic Nucleotide-Gated Ion (HCN) Channels Regulate PC12 Cell Differentiation Toward Sympathetic Neuron.

Hyperpolarization-activated cyclic nucleotide-gated ion channels (HCN channels) are widely expressed in the central and peripheral nervous systems and organs, while their functions are not well elucidated especially in the sympathetic nerve. The present study aimed to investigate the roles of HCN channel isoforms in the differentiation of sympathetic neurons using PC12 cell as a model. PC12 cells derived from rat pheochromocytoma were cultured and induced by nerve growth factor (NGF) (25 ng/ml) to differentiate to sympathetic neuron-like cells. Sympathetic directional differentiation of PC12 cells were evaluated by expressions of growth-associated protein 43 (GAP-43) (a growth cone marker), tyrosine hydroxylase (TH) (a sympathetic neuron marker) and neurite outgrowth. Results show that the HCN channel isoforms (HCN1-4) were all expressed in PC12 cells; blocking HCN channels with ivabradine suppressed NGF-induced GAP-43 expression and neurite outgrowth; silencing the expression of HCN2 and HCN4 using silenced using small interfering RNAs (siRNA), rather than HCN1 and HCN3, restrained GAP-43 expression and neurite outgrowth, while overexpression of HCN2 and HCN4 channels with gene transfer promoted GAP-43 expression and neurite outgrowth. Patch clamp experiments show that PC12 cells exhibited resting potentials (RP) of about -65 to -70 mV, and also presented inward HCN channel currents and outward (K+) currents, but no inward voltage-gated Na+ current was induced; NGF did not significantly affect the RP but promoted the establishment of excitability as indicated by the increased ability to depolarize and repolarize in the evoked suspicious action potentials (AP). We conclude that HCN2 and HCN4 channel isoforms, but not HCN1 and HCN3, promote the differentiation of PC12 cells toward sympathetic neurons. NGF potentiates the establishment of excitability during PC12 cell differentiation.