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Background: Pulmonary hypertension (PH) results in right ventricular (RV) dysfunction, subsequently leading to left ventricular (LV) impairment. The mechanism underlying ventricular interdependence is largely uninvestigated. Purpose: To explore the biventricular dysfunction and the ventricular interdependence in PH patients. Study Type: Retrospective. Population: One hundred and seven PH patients (mean pulmonary artery pressure >20 mmHg) and 72 age‐ and sex‐matched controls with cardiac magnetic resonance imaging (MRI) studies. Field Strength/Sequence: 3.0 T/balanced steady‐state free precession sequence. Assessment: LV and RV ejection fractions (EF) and RV and LV radial, circumferential, and longitudinal strains were assessed using commercial software. Strains were compared between controls, PH patients with preserved RVEF (RVEF ≥40%, N = 48), and PH patients with reduced RVEF (RVEF <40%, N = 59). Statistical Tests: Chi‐squared tests or Fisher's exact test, t tests or Mann–Whitney U test, one‐way ANOVA with Bonferroni's post hoc correction or Kruskal–Wallis test, Pearson or Spearman correlation, and multivariable linear regression analysis. A two‐tailed P < 0.05 was deemed statistically significant. Results: RV strain decreased sequentially from controls, through PH with preserved RVEF, to PH with reduced RVEF. PH patients with reduced RVEF had significantly lower LV strain, especially septal strain, and LV peak diastolic strain rate compared with both controls and PH patients with preserved RVEF. Multivariable analyses showed that RVEF was independently correlated with LV strain; furthermore, independent of RVEF, RV strain was significantly correlated with LV strain (LVGRS: β = 0.416; LVGCS: β = −0.371; LVGLS: β = 0.283). Data Conclusion: Subclinical impairment of RV function was found in PH with preserved RVEF. LV strain was impaired when RV was dysfunctional, which was associated with worsening RV strain. Therefore, while focusing on improving RV function, LV dysfunction in PH patients should also be monitored and treated early in order to slow the progression of the disease. Level of Evidence: 3 Technical Efficacy: Stage 3 [ABSTRACT FROM AUTHOR]

Background: Metabolic dysfunction‐associated fatty liver disease (MAFLD) was recently recognized as an important risk factor for cardiovascular diseases. Purpose: To examine the effect of MAFLD on cardiac function in metabolic syndrome by MRI. Study Type: Retrospective. Population: One hundred seventy‐nine patients with metabolic syndrome (MetS), 101 with MAFLD (MAFLD [+]) and 78 without (MAFLD [−]). Eighty‐one adults without any of the components of MetS or cardiac abnormalities were included as control group. Field Strength/Sequence: 3.0 T; balanced steady‐state free precession sequence. Assessment: Left atrial (LA) strain was assessed during three phases: reservoir strain (LA‐RS), conduit strain (LA‐CS), and booster strain (LA‐BS). Left ventricular (LV) global longitudinal (LV‐GLS) strain was also derived. The left atrioventricular coupling index (LACI) was calculated as the ratio of LA end‐diastolic volume (LA‐EDV) and LV‐EDV. Statistical Tests: Student's t test or Mann–Whitney U test; One‐way analysis of variance. A P value <0.05 was considered statistically significant. Results: Among MetS patients, individuals with MAFLD had significantly lower magnitude LV‐GLS (−11.6% ± 3.3% vs. −13.8% ± 2.7%) than those without MAFLD. For LA strains, LA‐RS (36.9% ± 13.7% vs. 42.9% ± 13.5%) and LA‐CS (20.0% ± 10.6% vs. 24.1% ± 9.2%) were also significantly reduced in MAFLD (+) compared to MAFLD (−). The LACIs (17.2% [12.9–21.2] % vs. 15.8% [12.2–19.7] %) were significantly higher in patients with MAFLD compared to those without MAFLD. After adjustment for other clinical factors, MAFLD was found to be independently correlated with LV‐GLS (β = −0.270) and LACI (β = 0.260). Data Conclusion: MAFLD had an unfavorable effect on LV myocardial strain in MetS. Moreover, LA strain and atrioventricular coupling were further impaired in patients with concomitant MAFLD compared to those without MAFLD. Last, MAFLD was independently associated with subclinical LV dysfunction and atrioventricular coupling after adjustment for other clinical factors. Evidence Level: 3 Technical Efficacy: 3 [ABSTRACT FROM AUTHOR]

Background: Aberrant activation of Wnt/β-catenin signaling by dysregulated post-translational protein modifications, especially ubiquitination is causally linked to cancer development and progression. Although Lys48-linked ubiquitination is known to regulate Wnt/β-catenin signaling, it remains largely obscure how other types of ubiquitination, such as linear ubiquitination governs its signaling activity. Methods: The expression and regulatory mechanism of linear ubiquitin chain assembly complex (LUBAC) on Wnt/β-catenin signaling was examined by immunoprecipitation, western blot and immunohistochemical staining. The ubiquitination status of β-catenin was detected by ubiquitination assay. The impacts of SHARPIN, a core component of LUBAC on malignant behaviors of gastric cancer cells were determined by various functional assays in vitro and in vivo. Results: Unlike a canonical role in promoting linear ubiquitination, SHARPIN specifically interacts with β-catenin to maintain its protein stability. Mechanistically, SHARPIN competes with the E3 ubiquitin ligase β-Trcp1 for β-catenin binding, thereby decreasing β-catenin ubiquitination levels to abolish its proteasomal degradation. Importantly, SHARPIN is required for invasiveness and malignant growth of gastric cancer cells in vitro and in vivo, a function that is largely dependent on its binding partner β-catenin. In line with these findings, elevated expression of SHARPIN in gastric cancer tissues is associated with disease malignancy and correlates with β-catenin expression levels. Conclusions: Our findings reveal a novel molecular link connecting linear ubiquitination machinery and Wnt/β-catenin signaling via SHARPIN-mediated stabilization of β-catenin. Targeting the linear ubiquitination-independent function of SHARPIN could be exploited to inhibit the hyperactive β-catenin signaling in a subset of human gastric cancers. [ABSTRACT FROM AUTHOR]

Background: The alteration of left atrial (LA) phasic function in subacute and chronic pulmonary embolism (PE) patients is unclear., Purpose: To investigate LA phasic strain and LA-right ventricular (RV) interaction in subacute and chronic PE patients with different degrees of obstruction by MRI-feature tracking (MRI-FT)., Study Type: Retrospective., Population: One hundred three PE patients (54 subacute [2 weeks to 3 months after initial symptoms], 49 chronic [>3 months after initial symptoms]) and 80 controls., Field Strength/sequence: 3.0 T/balanced steady state free precession sequence., Assessment: Patients were divided into mild (pulmonary artery obstruction index [PAOI] < 30%, N = 57), moderate (30% ≤ PAOI < 50%, N = 27), and severe (50% ≥ PAOI, N = 19) PE subgroups. LA reservoir, conduit, and active pump longitudinal strains (εs, εe, and εa) and strain rates (SRs, SRe, and SRa) and biventricular global strains were measured. Determinants of LA strains were investigated., Statistical Tests: ANOVA, t-tests, Mann-Whitney U tests, linear regression. P < 0.05 was considered statistically significant., Results: For both subacute and chronic PE patients, LA reservoir, conduit, and active pump strains and strain rates were significantly lower than in controls. However, there were no significant differences in LA strains between patients with subacute and chronic PE (P = 0.933, 0.625, and 0.630 for εs, εe, and εa). The severe PE subgroup had significantly higher εa and SRa than the mild and moderate PE subgroups. LA strains were significantly correlated with RV diameter and biventricular strains, and RV diameter (β = -6.836, -4.084, and -1.899 for εs, εe, and εa) was independently associated with LA strains after adjustment for other factors (R 2  = 0.627, 0.536, and 0.437 for εs, εe, and εa)., Data Conclusion: LA phasic function evaluated by MRI-FT was significantly impaired in subacute and chronic PE patients, and LA active pump function in the severe PE subgroup was higher than that in the mild and moderate PE subgroups. The independent association between RV diameter and LA strains demonstrates that RV diameter may be an important indicator for monitoring LA dysfunction in PE patients., Evidence Level: 3 TECHNICAL EFFICACY: Stage 3., (© 2024 International Society for Magnetic Resonance in Medicine.)