Angiotensin II type-2 receptor signaling facilitates liver injury repair and regeneration via inactivation of Hippo pathway.

The angiotensin II type 2 receptor (AT2R) is a well-established component of the renin-angiotensin system and is known to counteract classical activation of this system and protect against organ damage. Pharmacological activation of the AT2R has significant therapeutic benefits, including vasodilation, natriuresis, anti-inflammatory activity, and improved insulin sensitivity. However, the precise biological functions of the AT2R in maintaining homeostasis in liver tissue remain largely unexplored. In this study, we found that the AT2R facilitates liver repair and regeneration following acute injury by deactivating Hippo signaling and that interleukin-6 transcriptionally upregulates expression of the AT2R in hepatocytes through STAT3 acting as a transcription activator binding to promoter regions of the AT2R. Subsequently, elevated AT2R levels activate downstream signaling via heterotrimeric G protein Gα12/13-coupled signals to induce Yap activity, thereby contributing to repair and regeneration processes in the liver. Conversely, a deficiency in the AT2R attenuates regeneration of the liver while increasing susceptibility to acetaminophen-induced liver injury. Administration of an AT2R agonist significantly enhances the repair and regeneration capacity of injured liver tissue. Our findings suggest that the AT2R acts as an upstream regulator in the Hippo pathway and is a potential target in the treatment of liver damage.

Native T1 mapping for characterization of acute and chronic myocardial infarction in swine: Comparison with contrast-enhanced MRI.

BACKGROUND: Both acute and chronic myocardial infarction (AMI and CMI, respectively) exhibit delayed enhancement; however, clinical decision-making processes frequently require the differentiation of these two types of myocardial injury. PURPOSE: To investigate the reliability of AMI and CMI characterization using native T1 mapping and its feasibility for discriminating AMI from CMI. STUDY TYPE: Case-control. ANIMAL MODEL: The study cohort comprised 12 AMI (mean post-MI, 3.75 ± 1.29 days) and 15 CMI (mean post-MI, 39.53 ± 6.10 days) Bama mini-pigs. FIELD STRENGTH/SEQUENCE: Balanced steady-state free precession (bSSFP), segmented-turbo-FLASH-PSIR, and modified Look-Locker inversion recovery (MOLLI) sequences at 3.0T. ASSESSMENT: The infarct sizes were compared on matching short-axis slices of late-gadolinium-enhanced (LGE) images and T1 maps by two experienced radiologists. STATISTICAL TESTS: The infarct sizes were compared on matching short-axis slices of LGE images and T1 maps, and agreement was determined using linear regression and Bland-Altman analyses. The native T1 values were compared between AMI and CMI models (independent sample t-test). The intraclass correlation coefficient was used to assess inter- and intraobserver variability. RESULTS: Measured infarct sizes did not differ between native T1 mapping and LGE images (AMI: P = 0.913; CMI: P = 0.233), and good agreement was observed between the two techniques (AMI: bias, -3.38 ± 19.38%; R2 = 0.96; CMI: bias, -10.55 ± 10.90%; R2 = 0.90). However, the native infarction myocardium T1 values and the T1 signal intensity ratio of infarct and remote myocardium (T1 SI ratio) did not differ significantly between AMI and CMI (P = 0.173). DATA CONCLUSION: Noncontrast native T1 mapping can accurately determine acute and chronic infarct areas as well as conventional LGE imaging; however, it cannot distinguish acute from chronic MI. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1406-1414.