scholarly journals Cardiovascular Histopathology of a 11-Year Old with Mucopolysaccharidosis VII Demonstrates Fibrosis, Macrophage Infiltration, and Arterial Luminal Stenosis

2017 ◽  
pp. 31-37 ◽  
Author(s):  
Valerie Lew ◽  
Louis Pena ◽  
Robert Edwards ◽  
Raymond Y. Wang
Keyword(s):  
Macrophage Infiltration ◽  
Luminal Stenosis

PHENOTYPIC HETEROGENEITY OF CARDIAC MACROPHAGES DURING WOUND HEALING FOLLOWING MYOCARDIAL INFARCTION: PERSPECTIVES IN CLINICAL RESEARCH

2018 ◽  
Vol 33 (2) ◽  
pp. 70-76 ◽  
Author(s):  
A. E. Gombozhapova ◽  
Yu. V. Rogovskaya ◽  
M. S. Rebenkova ◽  
J. G. Kzhyshkowska ◽  
V. V. Ryabov
Keyword(s):  
Myocardial Infarction ◽  
Wound Healing ◽  
Cardiac Remodeling ◽  
Phenotypic Heterogeneity ◽  
Macrophage Infiltration ◽  
Myocardial Regeneration ◽  
Control Group ◽  
M2 Macrophage ◽  
Inflammatory Phase ◽  
Regenerative Phase

Purpose. Myocardial regeneration is one of the most ambitious goals in prevention of adverse cardiac remodeling. Macrophages play a key role in transition from inflammatory to regenerative phase during wound healing following myocardial infarction (MI). We have accumulated data on macrophage properties ex vivo and in cell culture. However, there is no clear information about phenotypic heterogeneity of cardiac macrophages in patients with MI. The purpose of the project was to assess cardiac macrophage infiltration during wound healing following myocardial infarction in clinical settings taking into consideration experimental knowledge.Material and Methods. The study included 41 patients with fatal MI type 1. In addition to routine analysis, macrophages infiltration was assessed by immunohistochemistry. We used CD68 as a marker for the cells of the macrophage lineage, while CD163, CD206, and stabilin-1 were considered as M2 macrophage biomarkers. Nine patients who died from noncardiovascular causes comprised the control group.Results. The intensity of cardiac macrophage infiltration was higher during the regenerative phase than during the inflammatory phase. Results of immunohistochemical analysis demonstrated the presence of phenotypic heterogeneity of cardiac macrophages in patients with MI. We noticed that numbers of CD68+, CD163+, CD206+, and stabilin-1+ macrophages depended on MI phase.Conclusion. Our study supports prospects for implementation of macrophage phenotyping in clinic practice. Improved understanding of phenotypic heterogeneity might become the basis of a method to predict adverse cardiac remodeling and the first step in developing myocardial regeneration target therapy.

Study on Vitamin D deficiency in patients of diabetes mellitus presenting with Acute Coronary syndrome in a tertiary care hospital in South India

2020 ◽  
Vol 11 (5) ◽  
pp. 49-53
Author(s):  
Archana Bhat ◽  
Arunachalam Ramachandran ◽  
Pradeep Periera ◽  
Akshatha Rao Aroor
Keyword(s):  
Diabetes Mellitus ◽  
Coronary Artery Disease ◽  
Vitamin D ◽  
Acute Coronary Syndrome ◽  
Coronary Artery ◽  
Vitamin D Deficiency ◽  
Coronary Syndrome ◽  
Vitamin D Levels ◽  
Luminal Stenosis ◽  
Artery Disease

Background: Vitamin D, a fat-soluble vitamin has its receptor present in myriad of tissues and it modulates multiple cellular processes. Vitamin D deficiency is reported to be associated with coronary artery disease. Cardiovascular disease is the leading cause of mortality worldwide. Aims and Objective: The primary outcome was to investigate if there is a correlation of 25-OH levels with the percentage of luminal stenosis, as measured with coronary angiogram. The secondary outcome was to determine the differences in angiographically proven luminal stenosis across categories of 25-OH vitamin D levels. Materials and Methods: Thirty patients with acute coronary syndrome with diabetes mellitus were included in this cross-sectional descriptive study. All patients were tested for fasting vitamin D levels, fasting blood sugar, HbA1C and serum creatinine. Detailed history of the patients was recorded. Data was analyzed by the statistical software SPSS version 19 and p value <0.05 was considered significant. Statistical tests like Chi- square, independent t test and log regression was used. Results: In this study 30 patients undergoing coronary angiography for acute coronary syndrome, Vitamin D levels showed severe deficiency in 6.7% (2) cases while mild deficiency was seen in 50% of the cases. Patients with single vessel disease on the coronary angiogram had lower mean HbA1C (9.18) levels in our study. Patients with triple vessel disease had poorly controlled mean HbA1C levels (10.42). Conclusion: In this study we did not find any significant difference between the serum Vitamin D deficiency levels with patients with angiographic severity of the coronary artery disease. Patients with poorly controlled diabetes mellitus had more severe angiographic proven coronary artery disease.

scholarly journals FOXE1-Dependent Regulation of Macrophage Chemotaxis by Thyroid Cells In Vitro and In Vivo

2021 ◽  
Vol 22 (14) ◽  
pp. 7666
Author(s):  
Sara C. Credendino ◽  
Marta De Menna ◽  
Irene Cantone ◽  
Carmen Moccia ◽  
Matteo Esposito ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Immune Cells ◽  
Cancer Susceptibility ◽  
Macrophage Infiltration ◽  
M2 Macrophage ◽  
Thyroid Cells ◽  
Transcriptional Alterations ◽  
Cancer Phenotypes

Forkhead box E1 (FOXE1) is a lineage-restricted transcription factor involved in thyroid cancer susceptibility. Cancer-associated polymorphisms map in regulatory regions, thus affecting the extent of gene expression. We have recently shown that genetic reduction of FOXE1 dosage modifies multiple thyroid cancer phenotypes. To identify relevant effectors playing roles in thyroid cancer development, here we analyse FOXE1-induced transcriptional alterations in thyroid cells that do not express endogenous FOXE1. Expression of FOXE1 elicits cell migration, while transcriptome analysis reveals that several immune cells-related categories are highly enriched in differentially expressed genes, including several upregulated chemokines involved in macrophage recruitment. Accordingly, FOXE1-expressing cells induce chemotaxis of co-cultured monocytes. We then asked if FOXE1 was able to regulate macrophage infiltration in thyroid cancers in vivo by using a mouse model of cancer, either wild type or with only one functional FOXE1 allele. Expression of the same set of chemokines directly correlates with FOXE1 dosage, and pro-tumourigenic M2 macrophage infiltration is decreased in tumours with reduced FOXE1. These data establish a novel link between FOXE1 and macrophages recruitment in the thyroid cancer microenvironment, highlighting an unsuspected function of this gene in the crosstalk between neoplastic and immune cells that shape tumour development and progression.

Nucleolin Improves Heart Function During Recovery From Myocardial Infarction by Modulating Macrophage Polarization

2021 ◽  
pp. 107424842198957
Author(s):  
Yuting Tang ◽  
Xiaofang Lin ◽  
Cheng Chen ◽  
Zhongyi Tong ◽  
Hui Sun ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Early Phase ◽  
Heart Function ◽  
Macrophage Polarization ◽  
Late Phase ◽  
Macrophage Infiltration ◽  
Enzyme Linked Immunosorbent Assay ◽  
M2 Macrophage ◽  
M2 Macrophage Polarization ◽  
Nucleolin Expression

Background: Nucleolin has multiple functions within cell survival and proliferation pathways. Our previous studies have revealed that nucleolin can significantly reduce myocardial ischemia-reperfusion injury by promoting myocardial angiogenesis and reducing myocardial apoptosis. In this study, we attempted to determine the role of nucleolin in myocardial infarction (MI) injury recovery and the underlying mechanism. Methods: Male BALB/c mice aged 6–8 weeks were used to set up MI models by ligating the left anterior descending coronary artery. Nucleolin expression in the heart was downregulated by intramyocardial injection of a lentiviral vector expressing nucleolin-specific small interfering RNA. Macrophage infiltration and polarization were measured by real-time polymerase chain reaction, flow cytometry, and immunofluorescence. Cytokines were detected by enzyme-linked immunosorbent assay. Results: Nucleolin expression in myocardium after MI induction decreased a lot at early phase and elevated at late phase. Nucleolin knockdown impaired heart systolic and diastolic functions and decreased the survival rate after MI. Macrophage infiltration increased in the myocardium after MI. Most macrophages belonged to the M1 phenotype at early phase (2 days) and the M2 phenotype increased greatly at late phase after MI. Nucleolin knockdown in the myocardium led to a decrease in M2 macrophage polarization with no effect on macrophage infiltration after MI. Furthermore, Notch3 and STAT6, key regulators of M2 macrophage polarization, were upregulated by nucleolin in RAW 264.7 macrophages. Conclusions: Lack of nucleolin impaired heart function during recovery after MI by reducing M2 macrophage polarization. This finding probably points to a new therapeutic option for ischemic heart disease.

Intracoronary polarimetry for characterizing coronary plaque vulnerability in patients with coronary artery disease

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Otsuka ◽  
M Villiger ◽  
L.J.C Van Zandvoort ◽  
T Neleman ◽  
A Karanasos ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Roc Analysis ◽  
Macrophage Infiltration ◽  
Collagenolytic Activity ◽  
Funding Source ◽  
Plaque Vulnerability ◽  
Coronary Syndrome ◽  
Coronary Lesions ◽  
Artery Disease

Abstract Background Intracoronary polarimetry with polarization-sensitive (PS-) optical frequency domain imaging (OFDI) measures polarization properties, including birefringence and depolarization, in parallel with structural features of conventional OFDI (Figure 1A). Collagen, which imparts mechanical integrity to fibrous caps, and collagen-synthesizing smooth muscle cells exhibit elevated birefringence. Depolarization is increased by the presence of macrophages and lipid/necrotic cores. Purpose This study aimed to compare conventional OFDI and polarimetric signatures of coronary lesions between patients with acute coronary syndrome (ACS) and chronic coronary syndrome (CCS). Furthermore, we aimed to determine a birefringence cut-off value for identifying which fibrous caps belong to ACS culprit lesions. Methods This study consisted of 37 patients with ACS (n=23) or CCS (n=14). ACS culprit lesions (ACS-lesions) and CCS stenotic lesions (CCS-lesions) were included in the analysis (820 mm). Qualitative and quantitative conventional OFDI analysis included the presence of plaque rupture, macrophage infiltration, micro-vessels, thrombus, stenosis severity, fibrous cap thickness (FCT), lipid arc, lipid-burden and calcium-burden index. Birefringence and depolarization of the coronary lesions and fibrous caps were measured in the cross-sectional images showing the minimum FCT or minimum luminal area. Predictors of ACS-lesions were investigated by multivariate regression analysis. Receiver operating characteristic (ROC) analysis was used to determine the birefringence cut-off value identifying ACS fibrous caps (ACS-caps). Results There were no significant differences in clinical characteristics between the two groups, except for previous history of coronary artery disease. Compared to CCS-lesions, ACS-lesions featured higher lipid-burden index and maximum lipid arc (both p&lt;0.05). ACS-lesions featured lower birefringence and higher depolarization than CCS-lesions (p&lt;0.05). Multivariable regression demonstrated an independent association of birefringence with ACS-lesions (p&lt;0.05), even after adjusting for the conventional OFDI findings. Limiting the analysis to the fibrous caps, ACS-caps exhibited significantly lower birefringence (p&lt;0.05) and higher depolarization (p&lt;0.05) that CCS-caps. ROC analysis for differentiating ACS-caps from CCS-caps found that a birefringence value of 0.0004 results in a sensitivity and specificity of 88% and 82%, respectively (Figure 1B, AUC = 0.82). Conclusions Intracoronary polarimetry provides quantitative assessment of coronary lesions related to their composition. Birefringence was an independent robust predictor of ACS-lesions. Decreased birefringence and pronounced depolarization within the ACS-caps may indicate increased collagenolytic activity and macrophage infiltration, respectively. These results suggest that polarization properties may serve as quantitative imaging markers for assessing plaque vulnerability. Figure 1 Funding Acknowledgement Type of funding source: Other. Main funding source(s): This work was supported by the National Institutes of Health and by Terumo Corporation.

scholarly journals Optimization of Electrospun Poly(caprolactone) Fiber Diameter for Vascular Scaffolds to Maximize Smooth Muscle Cell Infiltration and Phenotype Modulation

Polymers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 643 ◽  
Author(s):  
Dae Geun Han ◽  
Chi Bum Ahn ◽  
Ji-Hyun Lee ◽  
Yongsung Hwang ◽  
Joo Hyun Kim ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Fiber Diameter ◽  
Electrospun Fiber ◽  
Electrospun Nanofibers ◽  
Macrophage Infiltration ◽  
Vsmc Proliferation ◽  
Vascular Scaffolds ◽  
Poly Caprolactone

Due to the morphological resemblance between the electrospun nanofibers and extracellular matrix (ECM), electrospun fibers have been widely used to fabricate scaffolds for tissue regeneration. Relationships between scaffold morphologies and cells are cell type dependent. In this study, we sought to determine an optimum electrospun fiber diameter for human vascular smooth muscle cell (VSMC) regeneration in vascular scaffolds. Scaffolds were produced using poly(caprolactone) (PCL) electrospun fiber diameters of 0.5, 0.7, 1, 2, 2.5, 5, 7 or 10 μm, and VSMC survivals, proliferations, infiltrations, and phenotypes were recorded after culturing cells on these scaffolds for one, four, seven, or 10 days. VSMC phenotypes and macrophage infiltrations into scaffolds were evaluated by implanting scaffolds subcutaneously in a mouse for seven, 14, or 28 days. We found that human VSMC survival was not dependent on the electrospun fiber diameter. In summary, increasing fiber diameter reduced VSMC proliferation, increased VSMC infiltration and increased macrophage infiltration and activation. Our results indicate that electrospun PCL fiber diameters of 7 or 10 µm are optimum in terms of VSMC infiltration and macrophage infiltration and activation, albeit at the expense of VSMC proliferation.

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