Accumulating evidence shows that tRNA-derived fragments are a novel class of functional small non-coding RNA; however, their roles in aortic dissection (AD) are still unknown. In this study, we found that 5 0 -tiRNA-Cys-GCA was significantly downregulated in human and mouse models of aortic dissection. The abnormal proliferation, migration, and phenotypic transition of vascular smooth muscle cells (VSMCs) played a crucial role in the initiation and progression of aortic dissection, with 5 0 -tiRNA-Cys-GCA as a potential phenotypic switching regulator, because its overexpression inhibited the proliferation and migration of VSMCs and increased the expression of contractile markers. In addition, we verified that signal transducer and activator of transcription 4 (STAT4) was a direct downstream target of 5 0 -tiRNA-Cys-GCA. We found that the STAT4 upregulation in oxidized low-density lipoprotein (ox-LDL)-treated VSMCs, which promoted cell proliferation, migration, and phenotypic transformation, was reversed by 5 0 -tiRNA-Cys-GCA. Furthermore, 5 0 -tiRNA-Cys-GCA treatment reduced the incidence and prevented the malignant process of angiotensin II-and b-aminopropionitrile-induced AD in mice. In conclusion, our findings reveal that 5 0 -tiRNA-Cys-GCA is a potential regulator of the AD pathological process via the STAT4 signaling pathway, providing a novel clinical target for the development of future treatment strategies for aortic dissection.
Background and ObjectivesThis study aimed to assess the changes of RA function in patients with obstructive sleep apnea syndrome (OSAS) using velocity vector imaging (VVI) and to evaluate the application of VVI technology.MethodsAccording to the apnea–hypopnea index (AHI), 71 patients with OSAS were divided into three groups: mild, moderate, and severe. A total of 30 cases of healthy subjects were enrolled as the control group. Digital images of apex four-chamber views were acquired to measure the right atrium (RA) linear dimensions and volume parameters including RA longitudinal diameter (RAL), transverse diameter (RAT), RA maximum volume (Vmax), RA minimum volume (Vmin), right atrial volume before contraction (Vpre). Right atrial volume parameters were corrected by body surface area (VImax, VImin, VIpre). The total right atrial emptying fraction (RATEF), right atrial passive emptying fraction (RAPEF), right atrial active contraction emptying fraction (RAAEF) were calculated. The VVI data measuring right atrial global strain (RA-GLS), right atrial strain rate in ventricular systolic phase (RA-SRs), right atrial strain rate in ventricular early diastolic phase (RA-SRe), right atrial strain rate in ventricular late diastolic phase (RA-SRa).Results RA linear dimensions and volume parameters in severe OSAS were higher than those of control group. RAPEF in severe group was lower than control group and mild OSAS group (t = 2.681, P = 0.021; t = 2.985, P = 0.011; respectively). RAAEF in OSAS moderate group was higher than that of control group (t = 3.006, P = 0.02), and without statistical difference (P > 0.05) in the severe OSAS group and the control group.RA-GLS in moderate OSAS group was significantly lower than that of control group (t = 2.333, P = 0.040) and reduced more obvious in the severe OSAS group (vs control, t = 3.25, P = 0.008, vs mild; t = 3.011, P = 0.012; respectively). RA-SRe in moderate and severe OSAS groups were lower than control group (t = 2.466, P = 0.031; t = 3.547, P = 0.005; respectively). RA-SRs of OSAS in severe group was lower than that of control and mild groups (t = 3.665, P = 0.004; t = 3.204, P = 0.008; respectively). RA-SRa in severe OSAS group was lower than that of control group (t = 2.425, P = 0.034).Multivariate regression analysis showed that RA-GLS and RA-SRe were independently correlated with AHI (t = − 2.738, P = 0.010; t = − 2.191, P = 0.036; respectively). ConclusionRA function was impaired in patients with OSAS. On hemodynamics, the change of RA function performed increased of reserve function, reduced pipeline function and increased of contraction function. However, the strain and strain rate reduced in different degree. RA-GLS and RA-SRe decreased the earliest, which suggested that strain and strain rate were the parameters which can reflect myocardial function damage earliest. VVI can more earlier and accurately detect myocardial dysfunction of right atrium in patients with OSAS, which is expected to be a worthy technique for early clinical therapy in patients with OSAS.
BackgroundPrevious studies have demonstrated that sustained hypoxia in people with obstructive sleep apnea (OSA) impairs upper airway muscle activity, but the underlying mechanism remains poorly understood. As autophagy acts as an important regulator under hypoxia stress, we performed an in vitro investigation of the effects of sustained hypoxia on autophagy of genioglossus muscle-derived stem cells (GG MDSC), an important component of the upper airway muscle.Material/MethodsGenioglossus MDSCs were obtained from Sprague-Dawley (SD) rats and identified by using immunofluorescence staining for CD34, Sca-1, and desmin. GG MDSCs were incubated under normoxic or sustained hypoxic conditions for different periods of time. Western blotting was used to detect LC3 and Beclin 1, which are 2 important proteins in autophagy flux, and autophagolysosomes accumulation was observed by transmission electron microscopy (TEM). The mRNA and protein levels of HIF-1α and BNIP3 were evaluated by RT-PCR and Western blot analysis, respectively.ResultsOur study shows that sustained hypoxia promotes the expression of LC3BII and Beclin 1 in GG MDSCs in a time-dependent manner. TEM showed an increased number of autophagolysosomes in GG MDSCs under sustained hypoxia for 12 and 24 h. In addition, hypoxia activated the HIF-1α/BNIP3 signal pathway both at protein levels (shown by Western blot) and at mRNA levels (shown by RT-PCR).ConclusionsOur study shows that sustained hypoxia promotes autophagy in GG MDSCs, and the HIF-1α/BNIP3 signal pathway was involved in this process.
BackgroundThe myocardial wall of the left ventricle is a complex, multilayered structure and is not homogenous. The aim of this study was to determine longitudinal strain (LS) in the three myocardial layers in normal pregnant women according to gestation proceedings.MethodsThe advanced two-dimensional speckle tracking echocardiography (2D STE) was performed on 62 women during each pregnancy trimester and 6 to 9 weeks after delivery, while 30 age-matched, healthy, nonpregnant women served as controls. LS on endocardial, mid-myocardial and epicardial layers at 18 cardiac segments were measured.ResultsAs gestation proceeded, all of layer-specific LS and global LS progressively decreased, which subsequently recovered postpartum (P < 0.05), and the LS gradient between inner and outer myocardium became greater, which reached its maximum in the late pregnancy. Peak systolic LS was the highest at endocardium and the lowest at epicardium, while the highest at the apical level and the lowest at the base (P < 0.05). In the early pregnancy and postpartum, LS at basal level was homogenous, meanwhile layer-specific LS showed significant differences at mid-ventricular and apical level throughout the progress of normal pregnancy (P < 0.05).ConclusionsUsing 2D STE, three-layer assessment of LS can be performed in pregnant women and shall give us new insights into the quantitative analysis of global and regional LV function during pregnancy. Future studies on the detection of pregnancy related heart disease would require these parameters as reference values for each time point of a normal pregnancy.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.