Background: Regulatory T cells (Tregs), traditionally recognized as potent suppressors of immune response, are increasingly attracting attention because of a second major function: residing in parenchymal tissues and maintaining local homeostasis. However, the existence, unique phenotype, and function of so-called tissue Tregs in the heart remain unclear. Methods: In mouse models of myocardial infarction (MI), myocardial ischemia/reperfusion injury, or cardiac cryoinjury, the dynamic accumulation of Tregs in the injured myocardium was monitored. The bulk RNA sequencing was performed to analyze the transcriptomic characteristics of Tregs from the injured myocardium after MI or ischemia/reperfusion injury. Photoconversion, parabiosis, single-cell T-cell receptor sequencing, and adoptive transfer were applied to determine the source of heart Tregs. The involvement of the interleukin-33/suppression of tumorigenicity 2 axis and Sparc (secreted acidic cysteine-rich glycoprotein), a molecule upregulated in heart Tregs, was further evaluated in functional assays. Results: We showed that Tregs were highly enriched in the myocardium of MI, ischemia/reperfusion injury, and cryoinjury mice. Transcriptomic data revealed that Tregs isolated from the injured hearts had plenty of differentially expressed transcripts in comparison with their lymphoid counterparts, including heart-draining lymphoid nodes, with a phenotype of promoting infarct repair, indicating a unique characteristic. The heart Tregs were accumulated mainly because of recruitment from the circulating Treg pool, whereas local proliferation also contributed to their expansion. Moreover, a remarkable case of repeatedly detected T-cell receptor of heart Tregs, more than that of spleen Tregs, suggests a model of clonal expansion. Besides, Helios ^high Nrp-1 ^high phenotype proved the mainly thymic origin of heart Tregs, with a small contribution of phenotypic conversion of conventional CD4 ⁺ T cells, proved by the analysis of T-cell receptor repertoires and conventional CD4 ⁺ T cells adoptive transfer experiments. The interleukin-33/suppression of tumorigenicity 2 axis was essential for sustaining heart Treg populations. Last, we demonstrated that Sparc, which was highly expressed by heart Tregs, acted as a critical factor to protect the heart against MI by increasing collagen content and boosting maturation in the infarct zone. Conclusions: We identified and characterized a phenotypically and functionally unique population of heart Tregs that may lay the foundation to harness Tregs for cardioprotection in MI and other cardiac diseases.

Aims: Facial features were associated with increased risk of coronary artery disease (CAD). We developed and validated a deep learning algorithm for detecting CAD based on facial photos. Methods and results: We conducted a multicentre cross-sectional study of patients undergoing coronary angiography or computed tomography angiography at nine Chinese sites to train and validate a deep convolutional neural network for the detection of CAD (at least one ≥50% stenosis) from patient facial photos. Between July 2017 and March 2019, 5796 patients from eight sites were consecutively enrolled and randomly divided into training (90%, n = 5216) and validation (10%, n = 580) groups for algorithm development. Between April 2019 and July 2019, 1013 patients from nine sites were enrolled in test group for algorithm test. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated using radiologist diagnosis as the reference standard. Using an operating cut point with high sensitivity, the CAD detection algorithm had sensitivity of 0.80 and specificity of 0.54 in the test group; the AUC was 0.730 (95% confidence interval, 0.699–0.761). The AUC for the algorithm was higher than that for the Diamond–Forrester model (0.730 vs. 0.623, P < 0.001) and the CAD consortium clinical score (0.730 vs. 0.652, P < 0.001). Conclusion: Our results suggested that a deep learning algorithm based on facial photos can assist in CAD detection in this Chinese cohort. This technique may hold promise for pre-test CAD probability assessment in outpatient clinics or CAD screening in community. Further studies to develop a clinical available tool are warranted.

BACKGROUND: Colchicine has been approved to reduce cardiovascular risk in patients with coronary heart disease on the basis of its potential benefits demonstrated in the COLCOT (Colchicine Cardiovascular Outcomes Trial) and LoDoCo2 (Low-Dose Colchicine 2) studies. Nevertheless, there are limited data available about the specific impact of colchicine on coronary plaques. METHODS: This was a prospective, single-center, randomized, double-blind clinical trial. From May 3, 2021, until August 31, 2022, a total of 128 patients with acute coronary syndrome aged 18 to 80 years with lipid-rich plaque (lipid pool arc >90°) detected by optical coherence tomography were included. The subjects were randomly assigned in a 1:1 ratio to receive either colchicine (0.5 mg once daily) or placebo for 12 months. The primary end point was the change in the minimal fibrous cap thickness from baseline to the 12-month follow-up. RESULTS: Among 128 patients, 52 in the colchicine group and 52 in the placebo group completed the study. The mean age of the 128 patients was 58.0±9.8 years, and 25.0% were female. Compared with placebo, colchicine therapy significantly increased the minimal fibrous cap thickness (51.9 [95% CI, 32.8 to 71.0] μm versus 87.2 [95% CI, 69.9 to 104.5] μm; difference, 34.2 [95% CI, 9.7 to 58.6] μm; P =0.006), and reduced average lipid arc (–25.2° [95% CI, –30.6° to –19.9°] versus –35.7° [95% CI, –40.5° to –30.8°]; difference, –10.5° [95% CI, –17.7° to –3.4°]; P =0.004), mean angular extension of macrophages (–8.9° [95% CI, –13.3° to –4.6°] versus –14.0° [95% CI, –18.0° to –10.0°]; difference, –6.0° [95% CI, –11.8° to –0.2°]; P =0.044), high-sensitivity C-reactive protein level (geometric mean ratio, 0.6 [95% CI, 0.4 to 1.0] versus 0.3 [95% CI, 0.2 to 0.5]; difference, 0.5 [95% CI, 0.3 to 1.0]; P =0.046), interleukin-6 level (geometric mean ratio, 0.8 [95% CI, 0.6 to 1.1] versus 0.5 [95% CI, 0.4 to 0.7]; difference, 0.6 [95% CI, 0.4 to 0.9]; P =0.025), and myeloperoxidase level (geometric mean ratio, 1.0 [95% CI, 0.8 to 1.2] versus 0.8 [95% CI, 0.7 to 0.9]; difference, 0.8 [95% CI, 0.6 to 1.0]; P =0.047). CONCLUSIONS: Our findings suggested that colchicine resulted in favorable effects on coronary plaque stabilization at optical coherence tomography in patients with acute coronary syndrome. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04848857.

Heart failure is a global problem with high hospitalization and mortality rates. Inflammation and immune dysfunction are involved in this disease. Owing to their unique function, regulatory T cells (Tregs) have reacquired attention recently. They participate in immunoregulation and tissue repair in the pathophysiology of heart failure. Tregs are beneficial in heart by suppressing excessive inflammatory responses and promoting stable scar formation in the early stage of heart injury. However, in chronic heart failure, the phenotypes and functions of Tregs changed. They transformed into an antiangiogenic and profibrotic cell type. In this review, we summarized the functions of Tregs in the development of chronic heart failure first. Then, we focused on the interactions between Tregs and their target cells. The target cells of Tregs include immune cells (such as monocytes/macrophages, dendritic cells, T cells, and B cells) and parenchymal cells (such as cardiomyocytes, fibroblasts, and endothelial cells). Next-generation sequencing and gene editing technology make immunotherapy of heart failure possible. So, prospective therapeutic approaches based on Tregs in chronic heart failure had also been evaluated.

Objective—: Inflammation occurs during the progression of abdominal aortic aneurysm (AAA). IL (interleukin)-33 is a pleiotropic cytokine with multiple immunomodulatory effects, yet its role in AAA remains unknown. Approach and Results—: Immunoblot, immunohistochemistry, and immunofluorescent staining revealed increased IL-33 expression in adventitia fibroblasts from mouse AAA lesions. Daily intraperitoneal administration of recombinant IL-33 or transgenic IL-33 expression ameliorated periaorta CaPO ₄ injury- and aortic elastase exposure–induced AAA in mice, as demonstrated by blunted aortic expansion, reduced aortic wall elastica fragmentation, enhanced AAA lesion collagen deposition, attenuated T-cell and macrophage infiltration, reduced inflammatory cytokine production, skewed M2 macrophage polarization, and reduced lesion MMP (matrix metalloproteinase) expression and cell apoptosis. Flow cytometry analysis, immunostaining, and immunoblot analysis showed that exogenous IL-33 increased CD4 ⁺ Foxp3 ⁺ regulatory T cells in spleens, blood, and aortas in periaorta CaPO ₄ -treated mice. Yet, ST2 deficiency muted these IL-33 activities. Regulatory T cells from IL-33–treated mice also showed significantly stronger activities in suppressing smooth muscle cell inflammatory cytokine and chemokine expression, macrophage MMP expression, and in increasing M2 macrophage polarization than those from vehicle-treated mice. In contrast, IL-33 failed to prevent AAA and lost its beneficial activities in CaPO ₄ -treated mice after selective depletion of regulatory T cells. Conclusions—: Together, this study established a role of IL-33 in protecting mice from AAA formation by enhancing ST2-dependent aortic and systemic regulatory T-cell expansion and their immunosuppressive activities.

Overactivated inflammatory responses contribute to adverse ventricular remodeling after myocardial infarction (MI). Regulatory B cells (Bregs) are a newly discovered subset of B cells with immunomodulatory roles in many immune and inflammation-related diseases. Our study aims to determine whether the expansion of Bregs exerts a beneficial effect on ventricular remodeling and explore the mechanisms involved. Here, we showed that adoptive transfer of Bregs ameliorated ventricular remodeling in a murine MI model, as demonstrated by improved cardiac function, decreased scar size and attenuated interstitial fibrosis without changing the survival rate. Reduced Ly6C^hi monocyte infiltration was found in the hearts of the Breg-transferred mice, while the infiltration of Ly6C^lo monocytes was not affected. In addition, the replenishment of Bregs had no effect on the myocardial accumulation of T cells or neutrophils. Mechanistically, Bregs reduced the expression of C–C motif chemokine receptor 2 (CCR2) in monocytes, which inhibited proinflammatory monocyte recruitment to the heart from the peripheral blood and mobilization from the bone marrow. Breg-mediated protection against MI was abrogated by treatment with an interleukin 10 (IL-10) antibody. Finally, IL-10 neutralization reversed the effect of Bregs on monocyte migration and CCR2 expression. The present study suggests a therapeutic value of Bregs in limiting ventricular remodeling after MI through decreasing CCR2-mediated monocyte recruitment and mobilization.