Cardiac Cell Therapy: Insights into the Mechanisms of Tissue Repair.

Stem cell-based cardiac therapies have been extensively studied in recent years. However, the efficacy of cell delivery, engraftment, and differentiation post-transplant remain continuous challenges and represent opportunities to further refine our current strategies. Despite limited long-term cardiac retention, stem cell treatment leads to sustained cardiac benefit following myocardial infarction (MI). This review summarizes the current knowledge on stem cell based cardiac immunomodulation by highlighting the cellular and molecular mechanisms of different immune responses to mesenchymal stem cells (MSCs) and their secretory factors. This review also addresses the clinical evidence in the field.

Plasma BNP Levels and Diuretics Use as Predictors of Cardiovascular Events in Patients with Myocardial Infarction and Impaired Glucose Tolerance.

PURPOSE: Although impaired glucose tolerance (IGT) promotes cardiovascular events, our Alpha-glucosidase-inhibitor Blocks Cardiac Events in Patients with Myocardial Infarction and Impaired Glucose Tolerance (ABC) study showed that alpha-glucosidase inhibitors do not prevent cardiovascular events in patients with myocardial infarction (MI) and IGT. The aim of the present study was to identify potential clinical factors for cardiovascular events in patients with MI and IGT. METHODS: Using the limitless-arity multiple testing procedure, an artificial intelligence (AI)-based data mining method, we analyzed 385,391 combinations of fewer than four clinical parameters. RESULTS: We identified 380 combinations predicting the occurrence of (1) all-cause hospitalization, (2) hospitalization due to worsening of heart failure (HF), (3) hospitalization due to non-fatal MI, and (4) hospitalization due to percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for stable angina among 385,391 combinations in 853 patients. Among these, either plasma BNP levels ≥ 200 pg/dl or diuretic use exclusively predicted (1) all-cause hospitalization, (2) hospitalization due to worsening of HF, and (3) hospitalization due to a non-fatal MI, with plasma BNP levels ≥ 200 pg/dl being the sole predictor of hospitalization due to PCI and CABG. Importantly, each finding was verified by independently drawn Kaplan-Meier curves, revealing the unexpected role of plasma BNP levels in the progression of coronary stenosis determined as the necessity of PCI and CABG for stable angina. CONCLUSIONS: In patients with MI and IGT, high plasma BNP levels predicted the occurrence of coronary stenosis, recurrent MI, and worsening of HF, whereas diuretic use did not predict the progression of coronary stenosis but non-fatal MI and worsening of HF.

Identification of the Mtus1 Splice Variant as a Novel Inhibitory Factor Against Cardiac Hypertrophy.

BACKGROUND: In cardiac hypertrophy and failure, there is a widespread alteration in mRNA splicing, but the role of splice variants in cardiac hypertrophy has not yet been fully elucidated. In this study, we used an exon array to identify novel splice variants associated with cardiac hypertrophy. METHODS AND RESULTS: We performed genome-wide exon array analysis and developed a splicing profile in murine hearts with hypertrophy induced by transverse aortic constriction for 8 weeks. Following global analysis of splice variants using the Mouse Exon 1.0 ST Array, we identified 46 spliced genes and narrowed our focus to 1 gene, mitochondrial tumor suppressor 1 (Mtus1), whose splice variants were registered in the NCBI RefSeq database. Notably, one of the splice variants Mtus1A was specifically upregulated, although the total expression of the Mtus1 gene remained unchanged. We showed that Mtus1A was localized in the mitochondria, and its expression level increased with the degree of cardiac hypertrophy. In cultured cardiomyocytes, Mtus1A overexpression reduced phenylephrine-induced reactive oxygen species production and consequent ERK phosphorylation, resulting in a decrease in both cell size and protein synthesis. In vivo, cardiac-specific Mtus1A transgenic mice showed left ventricle wall thinning and a reduced hypertrophic response to pressure overload and phenylephrine treatment. CONCLUSIONS: We found that Mtus1 is specifically spliced in hypertrophic hearts and that the Mtus1A variant has an inhibitory effect on cardiac hypertrophy. Mtus1A is, therefore, a possible diagnostic and therapeutic target for cardiac hypertrophy and failure.