Machine learning and experimental validation of novel biomarkers for hypertrophic cardiomyopathy and cancers.

Hypertrophic cardiomyopathy (HCM) is a hereditary cardiac disorder marked by anomalous thickening of the myocardium, representing a significant contributor to mortality. While the involvement of immune inflammation in the development of cardiac ailments is well-documented, its specific impact on HCM pathogenesis remains uncertain. Five distinct machine learning algorithms, namely LASSO, SVM, RF, Boruta and XGBoost, were utilized to discover new biomarkers associated with HCM. A unique nomogram was developed using two newly identified biomarkers and subsequently validated. Furthermore, samples of HCM and normal heart tissues were gathered from our institution to confirm the variance in expression levels and prognostic significance of GATM and MGST1. Five novel biomarkers (DARS2, GATM, MGST1, SDSL and ARG2) associated with HCM were identified. Subsequent validation revealed that GATM and MGST1 exhibited significant diagnostic utility for HCM in both the training and test cohorts, with all AUC values exceeding 0.8. Furthermore, a novel risk assessment model for HCM patients based on the expression levels of GATM and MGST1 demonstrated favourable performance in both the training (AUC = 0.88) and test cohorts (AUC = 0.9). Furthermore, our study revealed that GATM and MGST1 exhibited elevated expression levels in HCM tissues, demonstrating strong discriminatory ability between HCM and normal cardiac tissues (AUC of GATM = 0.79; MGST1 = 0.86). Our findings suggest that two specific cell types, monocytes and multipotent progenitors (MPP), may play crucial roles in the pathogenesis of HCM. Notably, GATM and MGST1 were found to be highly expressed in various tumours and showed significant prognostic implications. Functionally, GATM and MGST1 are likely involved in xenobiotic metabolism and epithelial mesenchymal transition in a wide range of cancer types. GATM and MGST1 have been identified as novel biomarkers implicated in the progression of both HCM and cancer. Additionally, monocytes and MPP may also play a role in facilitating the progression of HCM.

Comprehensive Analysis of Immune Cell Infiltration and M2-Like Macrophage Biomarker Expression Patterns in Atrial Fibrillation.

Background: Macrophages play a crucial role in the progression of AF, closely linked to atrial inflammation and myocardial fibrosis. However, the functions and molecular mechanisms of different phenotypic macrophages in AF are not well understood. This study aims to analyze the infiltration characteristics of atrial immune cells in AF patients and further explore the role and molecular expression patterns of M2 macrophage-related genes in AF. Methods: This study integrates single-cell and large-scale sequencing data to analyze immune cell infiltration and molecular characterization of the LAA in patients with AF, using SR as a control group. CIBERSORT assesses immune cell types in LAA tissues; WGCNA identifies signature genes; cell clustering analyzes cell types and subpopulations; cell communication explores macrophage interactions; hdWGCNA identifies M2 macrophage gene modules in AF. AF biomarkers are identified using LASSO and Random Forest, validated with ROC curves and RT-qPCR. Potential molecular mechanisms are inferred through TF-miRNA-mRNA networks and single-gene enrichment analyses. Results: Myeloid cell subsets varied considerably between the AF and SR groups, with a significant increase in M2 macrophages in the AF group. Signals of inflammation and matrix remodeling were observed in AF. M2 macrophage-related genes IGF1, PDK4, RAB13, and TMEM176B were identified as AF biomarkers, with RAB13 and TMEM176B being novel markers. A TF-miRNA-mRNA network was constructed using target genes, which are enriched in the PPAR signaling pathway and fatty acid metabolism. Conclusion: Over infiltration of M2 macrophages may be an important factor in the progression of AF. The M2 macrophage-related genes IGF1, RAB13, TMEM176B and PDK4 may regulate the progression of AF through the PPAR signaling pathway and fatty acid metabolism.

Icariin improves cardiac function and remodeling via the TGF-ß1/Smad signaling pathway in rats following myocardial infarction.

BACKGROUND: Postinfarction cardiac remodeling presents a compensatory mechanism aimed at mitigating congestive heart failure. It is distinguished by progressive dilatation and hypertrophy of the ventricular chambers, fibrotic alterations, and prolonged apoptosis of cardiomyocytes. The primary objective of this study was to assess the effects of icariin on myocardial fibrosis and ventricular remodeling in rats subjected to myocardial infarction (MI). METHODS: Male Sprague‒Dawley (SD) rats were subjected to randomization and subsequently divided into distinct groups: the control group, the sham group (undergoing sham operation), the MI group (experiencing ligation of the left anterior descending artery), and the icariin group. Within the icariin group, rats were further categorized into three different dose groups based on the administered icariin dosage: the MI30 group (30 mg/kg/day), the MI60 group (60 mg/kg/day), and the MI120 group (120 mg/kg/day). Cardiac function evaluation was carried out using echocardiography. Histological examinations, including hematoxylin and eosin (HE) staining, Masson staining, and immunohistochemistry studies, were conducted 90 days after the occurrence of MI. Additionally, Western blotting was employed to assess TGF-ß1, p-Smad2, and p-Smad3 levels. RESULTS: The administration of icariin revealed a noteworthy enhancement in cardiac function among rats afflicted with left anterior descending coronary artery (LAD) ligation. In comparison to the icariin groups, the MI group exhibited reduced EF and FS, along with elevated LVEDD and LVESD. Furthermore, the cardiac fibrosis levels in the MI group rats exhibited a considerable increase compared to those in the icariin group. Notably, the levels of Collagen I, Collagen III, MMP2, and MMP9 were significantly higher in the MI group than in the icariin group, with evident distinctions. Moreover, the expression levels of TGF-ß, IL-13, p-Smad2, and p-Smad3 were notably upregulated in the MI group compared to the icariin group. CONCLUSIONS: In an experimental rat model of MI, the administration of icariin resulted in the amelioration of both cardiac function and remodeling processes, operating through the intricate TGF-ß1/Smad signaling pathway.

Uterine intravascular leiomyomatosis involves the heart: a case report and literature review.

Background: Intravascular leiomyomatosis (IVL) of the uterus is extremely rare in clinical practice, often involving the pelvic and abdominal veins. Involvement of the heart and pulmonary arteries is rarer but can lead to severe clinical outcomes. It is difficult to diagnose the disease before operation, and most of them are found accidentally during the operation or postoperative pathology of uterine fibroids. This article will report a special case of IVL involving the heart, and comprehensively analyze and discuss the relevant domestic and foreign literature. Through real clinical cases, we hope to understand the core characteristics of this disease to guide clinical diagnosis and treatment. Case Description: Here, we present the case of a 47-year-old woman with intrauterine venous leiomyomatosis whose tumor had spread to the right atrium. The patient lacked any distinct clinical symptoms. During uterine fibroid surgery, the tumor bolt was unintentionally discovered. The combined utility of multiple disciplines resulted in total removal of the tumor thrombus in the patient's venous system and right atrium during the same procedure. Following surgery, the patient achieved a significant recovery. After a follow-up of 2 years, there was no sign of neoplasm recurrence. Conclusions: IVL mainly occurs in premenopausal women. The early clinical manifestations are non-specific, and preoperative diagnosis is difficult. In order to improve the preoperative diagnosis rate, preoperative examination should be strengthened for patients with large uterine fibroids, long duration, chest tightness, shortness of breath, syncope and other medical history. During the operation, the pelvic and abdominal vessels should be comprehensively explored, and all intravascular lesions should be removed at one time, especially for those involving the heart, which often requires multidisciplinary collaboration. Complete resection of the lesion is the key factor affecting the recurrence. Endocrine therapy is an option for postoperative treatment, and it is used selectively according to the specific condition of the patient to reduce the risk of recurrence.

Astragalus (Astragalus mongholicus) Improves Ventricular Remodeling via ESR1 Downregulation RhoA/ROCK Pathway.

Astragalus (Astragalus mongholicus) alleviates myocardial remodeling caused by hypertension. However, the detailed molecular mechanism is unclear. This study aims to investigate the effect of Astragalus on ventricular remodeling in ovariectomized spontaneous hypertensive rats (OVX-SHR).Female SHR/NCrl rats were subjected to bilateral ovariectomy to establish the OVX-SHR model and treated with Astragalus extract by gavage. The hemodynamics and cardiac function parameters were measured. HE and Masson staining were used to detect the pathological structure of myocardial remodeling and observe the hyperplasia of myocardial collagen fibers. The immunohistochemistry tested the level of α-SMA. The expression levels of inflammatory cytokines, IκB, p65, Cleaved-Caspase3, RhoA, and ROCK1/2 were detected using Western blot. The method of qRT-PCR measured the expression of matrix metalloproteinase (MMP-2 and MMP-9).Hemodynamic and cardiac function parameters were significantly improved after a high dose of Astragalus extract and Valsartan treatment. The myocardial integrity of the model group was significantly reduced, arranged loosely, and disordered, while the expression of α-SMA was increased. However, Astragalus extract and Valsartan treatments significantly reduced the pathological damage and α-SMA. The levels of TNF-α, IL-1ß, IL-6, TGF-ß, MMP-2, and MMP-9 in the model group were increased but decreased after Astragalus extract treatment. Adding an ESR1 inhibitor attenuated the improvement effect of Astragalus extract on myocardial remodeling and restored the expression of RhoA and ROCK1/2.Astragalus extract attenuates the cardiac damage in OVX-SHR by downregulating the RhoA/ROCK pathway through ESR1.

Bone Marrow Mesenchymal Stem Cell-Derived Exosomal microRNA-29b-3p Promotes Angiogenesis and Ventricular Remodeling in Rats with Myocardial Infarction by Targeting ADAMTS16.

An increasing amount of evidence has suggested that microRNA (miR) plays a role in myocardial infarction (MI). Our study aimed to discuss the impact of exosomal miR-29b-3p in MI by regulating A Disintegrin and Metalloproteinase with Thrombospondin Motifs 16 (ADAMTS16). Exosomes were extracted from bone marrow mesenchymal stem cells (BMSCs). In a rat model of MI, myocardial angiogenesis and ventricular remodeling-related factors, as well as myocardial fibrosis, collagen volume fraction (CVF), capillary density, level of vascular endothelial growth factor (VEGF), and apoptosis of cardiomyocytes, were tested. ADAMTS16 and miR-29b-3p levels in the myocardial tissue of MI rats were tested. miR-29b-3p expression was decreased and ADAMTS16 expression was increased in the myocardial tissue of MI rats. ADAMTS16 was a target gene of miR-29b-3p. Upregulated miR-29b-3p delivered by BMSC-derived exosomes improved myocardial angiogenesis and ventricular remodeling, reduced myocardial fibrosis and CVF, increased capillary density and VEGF expression, and suppressed apoptosis of cardiomyocytes in MI rats. ADAMTS16 overexpression accelerated MI in rats, and ADAMTS16 upregulation reversed the protective effects of miR-29b-3p upregulation on MI rats. Our study provides evidence that upregulated miR-29b-3p delivered by BMSC-secreted exosomes can improve myocardial angiogenesis and ventricular remodeling in rats with MI by targeting ADAMTS16.

Effects of Baicalin on Blood Pressure and Left Ventricular Remodeling in Rats with Renovascular Hypertension.

BACKGROUND This study aimed to explore the effect of baicalin, which is a kind of bioactive flavonoid, on blood pressure and left ventricular remodeling in rats with renovascular hypertension. MATERIAL AND METHODS A total of 40 male Wistar rats were randomly assigned into sham-operation (n=10) and renal hypertension model groups (2-kidney-1 clip; 2K-1C, n=30). The rats in the renal hypertension model group were randomly subdivided into 2K-1C (n=13) and 2K-1C/Baicalin groups (n=14). The cardiac function indexes were determined after 4 weeks. The morphological changes in the myocardial tissue were observed using hematoxylin and eosin and Masson staining. The myocardial apoptosis was detected using the terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling method, and the expression of C/EBP homologous protein and caspase-3 was monitored by Western blot. The expression of GRP78 and GRP94 in myocardial cells of rats was detected by qPCR and Western blot technology. RESULTS No significant change in blood pressure was observed in the 2K-1C/Baicalin group compared with the 2K-1C group, but the indexes of left ventricular remodeling significantly improved. Pathological myocardial fibrosis and expression of fibrosis-related factors significantly decreased in the 2K-1C/Baicalin group compared with the 2K-1C group. The expression of glucose-regulated protein (GRP)78, GRP94, CHOP, and caspase-3, and apoptosis of cardiomyocytes also decreased in the 2K-1C/Baicalin group. CONCLUSIONS Baicalin has no significant antihypertensive effect, but reduced pathological changes in the myocardium, alleviated endoplasmic reticulum stress, and reduced myocardial apoptosis, reverting left ventricular remodeling in rats with renovascular hypertension.