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Background: Adverse left ventricular remodeling and subsequent heart failure remain a major cause of patient morbidity and mortality worldwide. The KLF family of transcription factors plays crucial roles in heart injury. KLF12 (Krüppel-like factor 12) is a transcription factor that regulates multiple disease processes, although the specific role of KLF12 in cardiac remodeling remains unclear., Methods and Results: In our study, we observed a significant upregulation of KLF12 expression in remodeling hearts. The increased expression of KLF12 primarily originated from cardiac fibroblasts during the fibrotic response induced by angiotensin II. To investigate the effects of KLF12, we performed RNA-seq and found that KLF12 overexpression significantly upregulated the cardiac remodeling associated pathway. Hence, we generated adult mice with cardiac fibroblast-specific overexpression of KLF12 using lentivirus or miRNA (miR-1/133TS) technology. Compared with control mice, KLF12-miR1/133TS transfected mice exhibited exacerbated cardiac remodeling and function. Mechanistically, we discovered that KLF12 directly binds to the promoter of Smad7, leading to the activation of the TGF-β (transforming growth factor beta)-Smad3 pathway., Conclusions: In conclusion, KLF12 promoted the development of angiotensin II-induced cardiac remodeling in male mice. Targeting KLF12 may be a promising therapeutic approach to treat cardiac remodeling.

Fibronectin (FN) can bind to certain integrin receptors on the cell surface through short peptide sequences, thereby transmitting extracellular stimuli to intracellular effector molecules. FNDC4 plays a similar role due to the constitution of a type III FN domain, which is a binding site for DNA, heparin, or cell surface. It mainly functions as a signal transmitter after being cleaved and secreted as the extracellular N-terminal fibronectin type III domain (sFNDC4). Emerging studies have shown that FNDC4 plays crucial roles in numerous diseases and holds significant implications for guiding clinical treatment. This review aims to summarize the different roles and the latest advances of FNDC4 in the development of various diseases, in order to provide new ideas for clinical treatment.

Background: Distinguishing light-chain cardiac amyloidosis (AL CA) from left ventricular wall thickening (LVWT) resulted from other etiologies has proven to be challenging. This study aimed to determine the sensitivity and specificity of relative apical sparing in diagnosing AL CA and investigate the differences in clinical and echocardiographic characteristics between AL CA patients with apical sparing and those with non-apical sparing., Methods: A total of 63 consecutive patients with AL CA, 102 consecutive patients with LVWT (including 51 hypertrophic cardiomyopathy (HCM) and 51 hypertension) and 33 healthy individuals were recruited retrospectively at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. Conventional and speckle tracking echocardiography were performed on all subjects., Results: Although wall thickening was observed in all patients, almost all functional parameters were worse in AL CA, except for relative apical longitudinal strain (LS) (P=0.906). Of 63 patients with AL CA, only 17.5% (n=11) showed an apical sparing pattern. Patients with apical sparing had poorer cardiac performance than those with non-apical sparing. Relative apical sparing showed the lowest diagnostic accuracy with an area under the curve (AUC) of 0.58 [95% confidence interval (CI): 0.49-0.67, sensitivity: 17.5%, specificity: 98.0%, P=0.095] to detect AL CA, but right ventricular strain (RVS) (AUC: 0.86, P<0.001) showed the highest among all echocardiographic parameters. When diagnosing AL CA patients with non-apical sparing, RVS continued to maintain excellent diagnostic accuracy (AUC: 0.84, P<0.001), followed by left atrial reservoir strain (LASr) (AUC: 0.77, P<0.001)., Conclusions: The diagnostic value of relative apical sparing for AL CA was limited with low sensitivity. In clinical practice, the diagnosis of early AL CA patients should not solely rely on relative apical sparing., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-1292/coif). The authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Aging-related cardiac dysfunction poses a major risk factor of mortality for elderly populations, however, efficient treatment for aging-related cardiac dysfunction is far from being known. Isthmin-1 (ISM1) is a novel adipokine that promotes glucose uptake and acts indispensable roles in restraining inflammatory and fibrosis. The present study aims to investigate the potential role and molecular mechanism of ISM1 in aging-related cardiac dysfunction. Aged and matched young mice were overexpressed or silenced with ISM1 to investigate the role of ISM1 in aging-related cardiac dysfunction. Moreover, H9C2 cells were stimulated with D-galactose (D-gal) to examine the role of ISM1 in vitro. Herein, we found that cardiac-specific overexpression of ISM1 significantly mitigated insulin resistance by promoting glucose uptake in aging mice. ISM1 overexpression alleviated while ISM1 silencing deteriorated cellular senescence, cardiac inflammation, and dysfunction in natural and accelerated cardiac aging. Mechanistically, ISM1 promoted glycolysis and activated Sirtuin-1 (SIRT1) through increasing glucose uptake. ISM1 increased glucose uptake via translocating GLUT4 to the surface, thereby enhancing glycolytic flux and hexosamine biosynthetic pathway (HBP) flux, ultimately leading to increased SIRT1 activity through O-GlcNAc modification. ISM1 may serve as a novel potential therapeutic target for preventing aging-related cardiac disease in elderly populations. ISM1 prevents aging-related cardiac dysfunction by promoting glycolysis and enhancing SIRT1 deacetylase activity, making it a promising therapeutic target for aging-related cardiac disease.