Blockade of the Notch Signaling Pathway Promotes M2 Macrophage Polarization to Suppress Cardiac Fibrosis Remodeling in Mice With Myocardial Infarction

Myocardial infarction (MI) is regarded as a serious ischemic heart disease on a global level. The current study set out to explore the mechanism of the Notch signaling pathway in the regulation of fibrosis remodeling after the occurrence of MI. First, experimental mice were infected with recombination signal binding protein J (RBP-J) shRNA and empty adenovirus vector, followed by the establishment of MI mouse models and detection of cardiac function. After 4 weeks of MI, mice in the sh-RBP-J group were found to exhibit significantly improved cardiac function relative to the sh-NC group. Moreover, knockdown of RBP-J brought about decreased infarct area, promoted cardiac macrophages M2 polarization, reduced cardiac fibrosis, and further decreased transcription and protein expressions of inflammatory factors and fibrosis-related factors. Furthermore, downregulation of cylindromatosis (CYLD) using si-CYLD reversed the results that knockdown of RBP-J inhibited fibrogenesis and the release of inflammatory factors. Altogether, our findings indicated that the blockade of Notch signaling promotes M2 polarization of cardiac macrophages and improves cardiac function by inhibiting the imbalance of fibrotic remodeling after MI.

Pathogenic characteristics of pulmonary infection in hospitalized patients with chronic heart failure and diagnostic value of sTREM-1, sCD163, and sTWEAK

Objective: To investigate the pathogenic characteristics of pulmonary infection in hospitalized patients with chronic heart failure as well as the diagnostic value of soluble myeloid cell expression triggering receptor-1 (sTREM-1), soluble CD163 (sCD163) and soluble tumor necrosis factor-like weak inducing factor (sTWEAK). Methods: A total of 72 patients with pulmonary infection who were hospitalized with chronic heart failure from December 2017 to December 2019 in the Department of Cardiology of Hebei Baoding Huaying Hospital of Traditional Chinese Medicine, China, were selected as the infection group, seventy-two patients without pulmonary infection who were hospitalized with chronic heart failure were selected as the non-infection group, and 50 healthy subjects who underwent physical examination in the hospital during the same period were selected as the control group. The distribution characteristics of pathogens in the infection group were statistically analyzed. The levels of sTREM-1, S CD163 and STweak in serum of patients with different infection severity and different cardiac function grades were compared among the three groups. Receiver operating characteristic curve (ROC) was utilized to evaluate the predictive value of the three indicators for the adverse prognosis of patients in hospital. Results: A total of 76 strains of pathogens were cultured from two hospitalized patients with pulmonary infection of chronic heart failure, among which 43 strains (56.58%) were gram-negative bacteria, 29 strains (38.15%) were gram-positive bacteria, and four strains (5.26%) were fungi. The levels of sTREM-1 and sCD163 in the control group, non-infection group and infection group were gradually increased (p<0.05), while there was no difference in sTWEAK between the infection group and the non-infection group (p>0.05). In the infection group, the expression levels of sTREM-1 and sCD163 increased with the severity of infection, with statistically significant differences (p<0.05), while there was no statistically significant difference in the expression level of sTWEAK among different infection severity (p>0.05). The higher the cardiac function grade of patients in the infection group, the higher the levels of sTREM-1 and sCD163, and the lower the level of sTWEAK, with a statistical significance (p<0.05). ROC analysis results showed that the serum sTREM-1, sCD163, and sTWEAK levels for the poor prognosis of patients with CHF combined with lung infection had areas under the curve of 0.864, 0.870, and 0.822, respectively, and the 95% CI values were 0.787-0.941, 0.795-0.945 and 0.733-0.910, respectively, all p<0.001. Conclusions: Pulmonary infection in hospitalized patients with chronic heart failure is mainly caused by gram-negative bacteria. Detection of sTREM-1, sCD163, and sTWEAK levels is of certain value in judging the condition and prognosis, which is worthy of clinical promotion. doi: https://doi.org/10.12669/pjms.38.3.4758 How to cite this:Zheng F. Pathogenic characteristics of pulmonary infection in hospitalized patients with chronic heart failure and diagnostic value of sTREM-1, sCD163, and sTWEAK. Pak J Med Sci. 2022;38(3):---------. doi: https://doi.org/10.12669/pjms.38.3.4758 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Effect of Combined Endurance Training and MitoQ on Cardiac Function and Serum Level of Antioxidants, NO, miR-126, and miR-27a in Hypertensive Individuals

Objectives. Hypertension (HTN) is one of the most important risk factors for cardiovascular diseases. Despite advances in treatment and control of HTN, the prevalence of HTN is still increasing. MitoQ is a supplement that acts on mitochondria and attenuates reactive oxygen species (ROS), which plays an important role in cardiovascular health. miRNAs play an important role in the pathophysiology of HTN. We evaluated the effects of MitoQ supplementation and endurance training (ET), alone and in combination, on functional indices of the heart and serum levels of miR-126, miR-27a, antioxidants, and NO, in patients with HTN. Methods. In a double-blind randomized clinical trial, 52 male participants (age 40-55 years) were randomly divided into four groups ( n = 13 ) of placebo, MitoQ (20 mg/day, oral), ET (cycle ergometer, moderate intensity, 40-60% VO2 peak, heart rate 120-140 b/min, 45 min a day, three days/week for six weeks), and MitoQ+ET. Cardiac function indices were assessed by echocardiography before and after interventions. Results. Systolic blood pressure (SBP) significantly decreased in all intervention groups ( P < 0.001 ) while DBP ( P < 0.01 ) and LV hypertrophy ( P < 0.05 ) were significantly decreased only in the MitoQ+ET group. Serum levels of SOD, GPx, and NO and the level of miR-126 significantly increased in all treatment groups, while miR-27a reduced in the ET ( P < 0.05 ) and MitoQ+ET ( P < 0.01 ) groups. Conclusions. Compared to MitoQ and ET alone, their combination has more prominent improving effects on cardiac health and amelioration of BP in the patients with HTN. These effects are through miR-126 and miR-27a modulation and ameliorating mitochondrial ROS production.

PET Tracers for Imaging Cardiac Function in Cardio-oncology

Purpose of Review Successful treatment of cancer can be hampered by the attendant risk of cardiotoxicity, manifesting as cardiomyopathy, left ventricle systolic dysfunction and, in some cases, heart failure. This risk can be mitigated if the injury to the heart is detected before the onset to irreversible cardiac impairment. The gold standard for cardiac imaging in cardio-oncology is echocardiography. Despite improvements in the application of this modality, it is not typically sensitive to sub-clinical or early-stage dysfunction. We identify in this review some emerging tracers for detecting incipient cardiotoxicity by positron emission tomography (PET). Recent Findings Vectors labeled with positron-emitting radionuclides (e.g., carbon-11, fluorine-18, gallium-68) are now available to study cardiac function, metabolism, and tissue repair in preclinical models. Many of these probes are highly sensitive to early damage, thereby potentially addressing the limitations of current imaging approaches, and show promise in preliminary clinical evaluations. Summary The overlapping pathophysiology between cardiotoxicity and heart failure significantly expands the number of imaging tools available to cardio-oncology. This is highlighted by the emergence of radiolabeled probes targeting fibroblast activation protein (FAP) for sensitive detection of dysregulated healing process that underpins adverse cardiac remodeling. The growth of PET scanner technology also creates an opportunity for a renaissance in metabolic imaging in cardio-oncology research.