Public awareness of palliative care for heart failure in Japan: A cross-sectional study.

BACKGROUND: Palliative care (PC) benefits cancer patients and those with heart failure (HF), improving quality of life and symptom burden. Despite guidelines recommending the integration of PC into HF care, its use remains inadequate, partly due to insufficient public awareness. This study aimed to assess the public awareness of PC for HF in Japan and identify factors associated with awareness. METHODS: A cross-sectional online survey was conducted from March 6-13, 2023, using a panel operated by Intage Inc. (Tokyo, Japan), which has a pool of 3.78 million potential Japanese respondents. The survey included 51,790 participants, matched for sex, age, and region of residence. Participants were asked about their awareness of PC eligibility for HF, along with demographic information, history of hospitalization for sudden illness, outpatient visits, and health status in the previous 2 years. The χ2 test and Cramer's V were used to analyze associations between awareness and variables, and multivariate logistic regression was used to estimate awareness predictors. RESULTS: In total, 91 % of participants were unaware of PC eligibility for HF. Age group, healthcare professional occupation, and history of hospitalization for acute myocardial infarction, acute HF, acute pulmonary embolism, and ruptured aortic aneurysm had weak to moderate associations with awareness. Multivariate analysis revealed that a history of hospitalization for sudden cardiovascular illness and being a healthcare professional were positively related to awareness, while age, female sex, and being married were associated with lower odds of awareness. CONCLUSION: The low public awareness of PC for HF in Japan underscores the importance of increasing awareness of the eligibility of PC for HF, as well as cancer, to integrate PC into HF practice as basic care.

NF-κB-dependent increase in tissue factor expression is responsible for hypoxic podocyte injury.

BACKGROUND: Fibrin deposition within glomeruli is commonly seen in kidney biopsy specimens, suggesting enhanced coagulant activity. Tissue factor (TF) is a coagulation factor which is also related to various biological effects, and TF is upregulated by hypoxia in cancer cells. Recently, hypoxic podocyte injury has been proposed, therefore, we investigated TF expression in hypoxia. METHODS: Conditionally immortalized human podocytes were differentiated and treated under hypoxic or normoxic conditions. mRNA expressions of TF and tissue factor pathway inhibitor (TFPI) were analyzed by quantitative RT-PCR. Protein levels of TF and TFPI were tested by enzyme-linked immunosorbent assay. We employed small interfering RNA (siRNA) to temporary knockdown early growth response protein 1 (Egr-1), hypoxia-inducible factor-1α (HIF-1α) and TF. The expression of CD2-associated protein (CD2AP) mRNA and phalloidin staining was examined to assess podocyte injury. RESULTS: Hypoxia increased mRNA expression of TF (6 h: 2.3 ± 0.05 fold, p < 0.001, 24 h: 5.6 ± 2.4 fold, p < 0.05) and suppressed TFPI (6 h: 0.54 ± 0.04 fold, p < 0.05, 24 h: 0.24 ± 0.06 fold, p < 0.001) compared with normoxia. Similarly, protein levels of TF were increased and TFPI were decreased. Egr-1 siRNA did not change TF mRNA expression. Pyrrolidine dithiocarbamate (PDTC), a nuclear factor kappa B (NF-κB) inhibitor, significantly reduced hypoxia induced TF expression, and HIF-1α knockdown further increased TF. Hypoxia resulted in decreased CD2AP and actin reorganization in podocytes, and these changes were attenuated by TF siRNA. CONCLUSION: Hypoxia increased the expression of TF in human podocytes NF-κB dependently. TF may have a critical role in the hypoxic podocyte injury.

Enhanced p122RhoGAP/DLC-1 Expression Can Be a Cause of Coronary Spasm.

BACKGROUND: We previously showed that phospholipase C (PLC)-δ1 activity was enhanced by 3-fold in patients with coronary spastic angina (CSA). We also reported that p122Rho GTPase-activating protein/deleted in liver cancer-1 (p122RhoGAP/DLC-1) protein, which was discovered as a PLC-δ1 stimulator, was upregulated in CSA patients. We tested the hypothesis that p122RhoGAP/DLC-1 overexpression causes coronary spasm. METHODS AND RESULTS: We generated transgenic (TG) mice with vascular smooth muscle (VSM)-specific overexpression of p122RhoGAP/DLC-1. The gene and protein expressions of p122RhoGAP/DLC-1 were markedly increased in the aorta of homozygous TG mice. Stronger staining with anti-p122RhoGAP/DLC-1 in the coronary artery was found in TG than in WT mice. PLC activities in the plasma membrane fraction and the whole cell were enhanced by 1.43 and 2.38 times, respectively, in cultured aortic vascular smooth muscle cells from homozygous TG compared with those from WT mice. Immediately after ergometrine injection, ST-segment elevation was observed in 1 of 7 WT (14%), 6 of 7 heterozygous TG (84%), and 7 of 7 homozygous TG mice (100%) (p<0.05, WT versus TGs). In the isolated Langendorff hearts, coronary perfusion pressure was increased after ergometrine in TG, but not in WT mice, despite of the similar response to prostaglandin F2α between TG and WT mice (n = 5). Focal narrowing of the coronary artery after ergometrine was documented only in TG mice. CONCLUSIONS: VSM-specific overexpression of p122RhoGAP/DLC-1 enhanced coronary vasomotility after ergometrine injection in mice, which is relevant to human CSA.