WWP1 Deficiency Alleviates Cardiac Remodeling Induced by Simulated Microgravity.

Cardiac muscle is extremely sensitive to changes in loading conditions; the microgravity during space flight can cause cardiac remodeling and function decline. At present, the mechanism of microgravity-induced cardiac remodeling remains to be revealed. WW domain-containing E3 ubiquitin protein ligase 1 (WWP1) is an important activator of pressure overload-induced cardiac remodeling by stabilizing disheveled segment polarity proteins 2 (DVL2) and activating the calcium-calmodulin-dependent protein kinase II (CaMKII)/histone deacetylase 4 (HDAC4)/myocyte-specific enhancer factor 2C (MEF2C) axis. However, the role of WWP1 in cardiac remodeling induced by microgravity is unknown. The purpose of this study was to determine whether WWP1 was also involved in the regulation of cardiac remodeling caused by microgravity. Firstly, we detected the expression of WWP1 and DVL2 in the heart from mice and monkeys after simulated microgravity using western blotting and immunohistochemistry. Secondly, WWP1 knockout (KO) and wild-type (WT) mice were subjected to tail suspension (TS) to simulate microgravity effect. We assessed the cardiac remodeling in morphology and function through a histological analysis and echocardiography. Finally, we detected the phosphorylation levels of CaMKII and HDAC4 in the hearts from WT and WWP1 KO mice after TS. The results revealed the increased expression of WWP1 and DVL2 in the hearts both from mice and monkeys after simulated microgravity. WWP1 deficiency alleviated simulated microgravity-induced cardiac atrophy and function decline. The histological analysis demonstrated WWP1 KO inhibited the decreases in the size of individual cardiomyocytes of mice after tail suspension. WWP1 KO can inhibit the activation of the DVL2/CaMKII/HDAC4 pathway in the hearts of mice induced by simulated microgravity. These results demonstrated WWP1 as a potential therapeutic target for cardiac remodeling and function decline induced by simulated microgravity.

Ckip-1 3'-UTR Attenuates Simulated Microgravity-Induced Cardiac Atrophy.

Microgravity prominently affected cardiovascular health, which was the gravity-dependent physical factor. Deep space exploration had been increasing in frequency, but heart function was susceptible to conspicuous damage and cardiac mass declined in weightlessness. Understanding of the etiology of cardiac atrophy exposed to microgravity currently remains limited. The 3'-untranslated region (UTR) of casein kinase-2 interacting protein-1 (Ckip-1) was a pivotal mediator in pressure overload-induced cardiac remodeling. However, the role of Ckip-1 3'-UTR in the heart during microgravity was unknown. We analyzed Ckip-1 mRNA 3'-UTR and coding sequence (CDS) expression levels in ground-based analogs such as mice hindlimb unloading (HU) and rhesus monkey head-down bed rest model. Ckip-1 3'-UTR had transcribed levels in the opposite change trend with cognate CDS expression in the hearts. We then subjected wild-type (WT) mice and cardiac-specific Ckip-1 3'-UTR-overexpressing mice to hindlimb unloading for 28 days. Our results uncovered that Ckip-1 3'-UTR remarkably attenuated cardiac dysfunction and mass loss in simulated microgravity environments. Mechanistically, Ckip-1 3'-UTR inhibited lipid accumulation and elevated fatty acid oxidation-related gene expression in the hearts through targeting calcium/calmodulin-dependent kinase 2 (CaMKK2) and activation of the AMPK-PPARα-CPT1b signaling pathway. These findings demonstrated Ckip-1 3'-UTR was an important regulator in atrophic heart growth after simulated microgravity.

Dataset for microstructure and mechanical properties of (CrCoNi)97Al1.5Ti1.5 medium entropy alloy twisted by free-end-torsion at room and cryogenic temperatures.

This data article presents the torsion parameters and the microstructural data of the (CrCoNi)97Al1.5Ti1.5 medium-entropy alloy (MEA). The data presented in this article are related to the research article entitled "Microstructure and mechanical properties of (CrCoNi)97Al1.5Ti1.5 medium entropy alloy twisted by free-end-torsion at room and cryogenic temperatures", see Ref. [1]. This article can be used for data analysis and interpretation and their comparison with other data sets in the research articles. The microstructure and the element distributions of the as-swaged rods were obtained using a scanning electron microscope (SEM) equipped with electron channelling contrast imaging (ECCI), electron diffraction spectroscopy (EDS) and electron backscattered diffraction (EBSD) detectors. The phases of the MEA before and after torsion are determined by the X-ray diffractometer (XRD) techniques. Optical micrograph, inverse pole figure (IPF) map, grain boundary map and misorientation angle distribution and pole figure of the as-swaged sample were presented. I In order to provide data reference for future torsion experiments, this article draws schematic diagrams of the hot-swaged rod, dimensions of the torsion/tensile specimens, liquid nitrogen (@LN) environment torsion device and schematic representation for characterization locations of microstructure. Lastly, Kernel Average Misorientation (KAM) maps and misorientation angle distribution of various samples or different strained layers were used for comparative analysis.