BACKGROUND: Pathological cardiac remodeling after myocardial infarction (MI) is a leading cause of heart failure and sudden death. The detailed mechanisms underlying the transition to heart failure after MI are not fully understood. Disruptions in the endoplasmic reticulum (ER)–mitochondria connectivity, along with mitochondrial dysfunction, are substantial contributors to this remodeling process. In this study, we aimed to explore the impact of mitochondrial tumor suppressor 1A (Mtus1A) on cardiac remodeling subsequent to MI and elucidate its regulatory role in ER-mitochondria interactions. METHODS: Single-nucleus RNA sequencing analysis was performed to delineate the expression patterns of mitochondrial tumor suppressor 1 (Mtus1) in human cardiomyocytes under ischemic stress. MI models were induced in mice by left coronary artery ligation and replicated in vitro using primary neonatal rat ventricular myocytes exposed to oxygen glucose deprivation. Cardiac-specific deletion of Mtus1 was achieved by crossing floxed Mtus1 mice with the Myh6-MerCreMer mice. The impact of Mtus1A, a mitochondrial isoform of Mtus1, on cardiac function and the molecular mechanisms were investigated in both in vivo and in vitro settings. Mitochondria-associated ER membranes (MAMs) coupling levels were evaluated by transmission electron microscopy and live-cell imaging. Protein interactions involving Mtus1A were explored through immunoprecipitation–mass spectrometry, coimmunoprecipitation, and proximity ligation assay. The roles of Mtus1A and Fbxo7 (F-box protein 7) were validated in a murine MI model using adeno-associated virus serotype 9 (AAV9). RESULTS: Bioinformatics analysis revealed a significant downregulation of Mtus1 expression in human cardiomyocytes under ischemic conditions, indicating its potential role in stress response. The predominant isoform in murine cardiomyocytes, Mtus1A, showed reduced expression in the left ventricle of mice after MI, which is consistent with the decreased levels of its orthologs in heart tissues from patients with MI. Cardiac-specific Mtus1-knockout mice exhibited worsened cardiac dysfunction after MI. Further studies demonstrated that Mtus1A partially localizes to MAMs, where it modulates MAMs coupling and preserves mitochondrial function. Mechanistically, Mtus1A functions as a scaffold protein that maintains the formation of inositol 1,4,5-trisphosphate receptor 1 (IP ₃ R1)–glucose-regulated protein 75 (Grp75)–voltage-dependent anion channel 1 (VDAC1) complex through its amino acid sequence 189-219. In addition, Mtus1A protein is stabilized by K6-linked ubiquitination through the E3 ubiquitin ligase Fbxo7. Mtus1A overexpression in mice mitigated MI-induced cardiac dysfunction and remodeling by maintaining MAMs integrity. CONCLUSIONS: Our study demonstrates that Mtus1A is crucial for modulating MI-induced cardiac remodeling by preserving ER-mitochondria communication and ameliorating mitochondrial function in cardiomyocytes. Mtus1A may serve as a potential therapeutic target for treating heart failure after MI.

Thrombus and restenosis after stent implantation are the major complications because traditional drugs such as rapamycin delay the process of endothelialization. Nitric oxide (NO) is mainly produced by endothelial nitric oxide synthase (eNOS) on the membrane of endothelial cells (ECs) in the cardiovascular system and plays an important role in vasomotor function. It strongly inhibits the proliferation of smooth muscle cells (SMCs) and ameliorates endothelial function when ECs get hurt. Inspired by this, introducing NO to traditional stent coating may alleviate endothelial insufficiency caused by rapamycin. Here, we introduced SNAP as the NO donor, mimicking how NO affects in vivo, into rapamycin coating to alleviate endothelial damage while inhibiting SMC proliferation. Through wicking effects, SNAP was absorbed into a hierarchical coating that had an upper porous layer and a dense polymer layer with rapamycin at the bottom. Cells were cultured on the coatings, and it was observed that the injured ECs were restored while the growth of SMCs further diminished. Genome analysis was conducted to further clarify possible signaling pathways: the effect of cell growth attenuated by NO may cause by affecting cell cycle and enhancing inflammation. These findings supported the idea that introducing NO to traditional drug-eluting stents alleviates incomplete endothelialization and further inhibits the stenosis caused by the proliferation of SMCs.

Predictive value of red blood cell distribution width in critically ill patients with atrial fibrillation: a retrospective cohort study Hongfen Zeng, Tingting Tao, Zetao Ma, Min Wang, Xue Lu, Yanbo Zhao, Zhida Shen

Knowledge of the antibody response to the third dose of inactivated SARS-CoV-2 vaccines is crucial because it is the subject of one of the largest global vaccination programs. This study integrated microsampling with optical biosensors to profile neutralizing antibodies (NAbs) in fifteen vaccinated healthy donors, followed by the application of machine learning to predict antibody response at given timepoints. Over a nine-month duration, microsampling and venipuncture were conducted at seven individual timepoints. A refined iteration of a fiber optic biolayer interferometry (FO-BLI) biosensor was designed, enabling rapid multiplexed biosensing of the NAbs of both wild-type and Omicron SARS-CoV-2 variants in minutes. Findings revealed a strong correlation (Pearson r of 0.919, specificity of 100%) between wild-type variant NAb levels in microsamples and sera. Following the third dose, sera NAb levels of the wild-type variant increased 2.9-fold after seven days and 3.3-fold within a month, subsequently waning and becoming undetectable after three months. Considerable but incomplete evasion of the latest Omicron subvariants from booster vaccine-elicited NAbs was confirmed, although a higher number of binding antibodies (BAbs) was identified by another rapid FO-BLI biosensor in minutes. Significantly, FO-BLI highly correlated with a pseudovirus neutralization assay in identifying neutralizing capacities (Pearson r of 0.983). Additionally, machine learning demonstrated exceptional accuracy in predicting antibody levels, with an error level of <5% for both NAbs and BAbs across multiple timepoints. Microsample-driven biosensing enables individuals to access their results within hours of self-collection, while precise models could guide personalized vaccination strategies. The technology’s innate adaptability means it has the potential for effective translation in disease prevention and vaccine development.

Background: Frailty is common among patients with coronary heart disease (CHD). This study aimed to examine both baseline frailty and its longitudinal changes in relation to the risk of major adverse cardiovascular events (MACEs) in patients with CHD. Methods: Data were sourced from the ARIC (Atherosclerosis Risk in Communities) study. Frailty status was assessed using a modified Fried frailty phenotype at 2 consecutive surveys. The outcome was MACEs, defined as a composite of recurrent CHD, incident heart failure, stroke, or cardiovascular death. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs. Results: In baseline frailty analyses, 1793 patients with CHD were included. Compared with robust patients, prefrail and frail patients had a higher risk of MACEs (HR, 1.24 [95% CI, 1.08–1.42] for prefrail; and HR, 1.75 [95% CI, 1.43–2.15] for frail). In frailty transition analyses, 862 patients with CHD were included. Patients who progressed from robust to prefrail/frail status had a higher MACE risk (HR, 1.43 [95% CI, 1.07–1.91]) compared with those who remained robust. Similarly, progression from prefrail to frail status was associated with an increased risk of MACEs (HR, 2.30 [95% CI, 1.62–3.27]) compared with stable prefrailty. Conversely, recovery from prefrail to robust status was related to a decreased MACE risk (HR, 0.62 [95% CI, 0.40–0.96]). Conclusions: Both baseline frailty and its temporal changes were associated with the risk of MACEs among patients with CHD, highlighting the clinical value of monitoring and intervening for frailty in CHD management.