The aim of the present study was to investigate the protective effect of Kruppel‑like factor 15 (KLF15) overexpression on heart failure (HF) induced by left ventricular (LV) pressure overload in mice. Wild‑type (WT) mice and cardiac‑specific KLF15‑overexpressed transgenic (TG) mice were selected as research subjects, and an LV pressure overload model was constructed by ascending aortic constriction surgery. Changes in cardiac morphology and function, and ultrastructure and molecular expression were observed via M‑mode echocardiography, histological and immunohistochemical staining, ELISA and western blotting at 2 and 6 weeks of LV overload. WT and TG mice subjected to 2 weeks of overload displayed adaptive LV hypertrophy characterized by ventricular thickness, cardiomyocyte size, ejection fraction and fractional shortening of heart‑lung weight ratio and KLF15, and increases in vascular endothelial growth factor (VEGF) expression without other pathological changes. WT mice subjected to 6 weeks of overload displayed enlargement of the LV chamber, severe interstitial remodeling, and HW/LW, cardiac capillary and heart function decline, accompanied by downregulated expression of KLF15 and VEGF, and upregulated expression of connective tissue growth factor, phosphorylated p38 (p‑p38) and phosphorylated Smad3 (p‑Smad3). In contrast, TG mice exhibited improved resistance to 6 weeks of overload and a slighter molecular expression response compared with WT mice. KLF15 was revealed to be a critical factor regulating the expression of CTGF, VEGF, p‑p38 and p‑Smad3, and could alleviate the progression from adaptive LV hypertrophy to decompensatory cardiac insufficiency.
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http://dx.doi.org/10.3892/mmr.2020.10913 | DOI Listing |
Biochim Biophys Acta Mol Basis Dis
January 2025
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China; Hubei Key Laboratory of Cardiology, Wuhan 430060, China. Electronic address:
Background: Cardiac hypertrophy is characterized by the upregulation of fetal genes, increased protein synthesis, and enlargement of cardiac myocytes. The mechanistic target of rapamycin complex 1 (mTORC1), which responds to fluctuations in cellular nutrient and energy levels, plays a pivotal role in regulating protein synthesis and cellular growth. While attempts to inhibit mTORC1 activity, such as through the application of rapamycin and its analogs, have demonstrated limited efficacy, further investigation is warranted.
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January 2025
Shandong Yankuang Intelligent Manufacturing Co., Jining, 272000, China.
The hydraulic column is a core component in the coal mine support system, however, the real-time monitoring of the hydraulic column during the service process of the hydraulic support faces challenges. To address these issues, a high-precision stress mapping method of hydraulic column is proposed. The hydraulic column loss function was constructed to guide the data-driven model training, and the cylinder stress mechanism model was established by using the elastic-plastic theory of thick-walled cylinder.
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January 2025
Cardiovascular Institute, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Heart failure with preserved ejection fraction (HFpEF) is increasingly common but its pathogenesis is poorly understood. The ability to assess genetic and pharmacologic interventions is hampered by the lack of robust preclinical mouse models of HFpEF. We developed a novel "two-hit" model, which combines obesity and insulin resistance with chronic pressure overload to recapitulate clinical features of HFpEF.
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January 2025
Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
Mitochondrial dysfunction is a key factor in exacerbating pressure overload-induced cardiac hypertrophy and is linked to increased morbidity and mortality. ECSIT, a crucial adaptor for inflammation and mitochondrial function, has been reported to express multiple transcripts in various species and tissues, leading to distinct protein isoforms with diverse subcellular localizations and functions. However, whether an unknown ECSIT isoform exists in cardiac cells and its potential role in regulating mitochondrial function and pathological cardiac hypertrophy has remained unclear.
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December 2024
School of Mechanical Engineering, Key Laboratory of Special Engine Technology, Ministry of Education, Nanjing University of Science and Technology, Nanjing, 210094, People's Republic of China.
In the field of gun launched missile extended range rocket, the propellant grain in the rocket needs to withstand significant launch loads during their firing phase, and also bear the high pressure caused by ignition, and the impact of launch overloads and ignition shocks on the structural integrity of propellants becomes very important. So this work investigated the dynamic initiation fracture toughness of the composite modified double-base (CMDB) propellant by both experiments and numerical simulations. The dynamic mechanical properties test of the cracked straight through flattened Brazilian disc (CSTFBD) specimens were conducted using a modified Split Hopkinson pressure bar (SHPB).
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