Presence Of Macrophage Infiltration Research Articles

Association of polarimetric signatures with coronary plaque composition in patients with acute and chronic coronary syndrome: an intravascular polarization-sensitive optical coherence tomography study

Abstract Background Intravascular polarimetry with polarization-sensitive (PS-) optical coherence tomography (OCT) measures polarization properties, birefringence and depolarization, in parallel with structural features available with conventional OCT (Figure 1). Birefringence is elevated in collagen and collagen-synthesizing smooth muscle cells, which imparts mechanical integrity to fibrous caps. Depolarization is elevated in the presence of macrophages and lipid/necrotic core. Purpose This study aimed to investigate polarimetric signatures of coronary lesions in patients with acute coronary syndrome (ACS) and chronic coronary syndrome (CCS). Furthermore, we aimed to investigate diagnostic value for birefringence and depolarization of ACS culprit lesions discriminating from CCS target lesions. Methods This was the first-in-human study of intracoronary PS-OCT in Japan, consisting of 17 patients with ACS (n = 5) or CCS (n = 12) who underwent intravascular PS-OCT. ACS culprit lesions (ACS-lesions) and CCS target lesions (CCS-lesions) were included in the analysis, resulting in a total of 862 cross-sections. In the cross-sectional images, lumen segmentation and guidewire artifact were automatically segmented. The median value of birefringence and depolarization were automatically analyzed using depolarization cut-off value (cross-sectional level). Birefringence and depolarization of ACS- and CCS-lesions were compared by using a generalized estimating equation model. Receiver operating characteristic (ROC) analysis was used to investigate diagnostic performance of polarimetric signatures for the identification of ACS-lesions. Results Compared to CCS-lesions, ACS-lesions featured higher lipid-burden index and maximum lipid arc (both p < 0.05). Compared to the CCS-lesions, ACS-lesions exhibited significantly lower birefringence (p < 0.05) and higher depolarization (p < 0.05) (Figure 2). In the ROC analysis for differentiating ACS-lesions from CCS-lesions, area under the curves (AUC) for birefringence and depolarization were 0.712 and 0.672, respectively. In the multivariable ROC analysis in diagnosing ACS lesions, combination of birefringence with depolarization improved the AUC to 0.755 (p ＝ 0.025). Conclusions Intravascular PS-OCT provides quantitative compositional assessment of coronary lesions. Decreased birefringence and pronounced depolarization within the ACS-lesions indicate increased collagenolytic activity and the presence of macrophage infiltration, respectively. These results suggest that polarization properties may serve as quantitative imaging markers for assessing natural history of coronary atherosclerosis.

Analysis of risk factors in high-risk plaque in acute coronary syndrome based on LASSO regression

Abstract Background The CLIMA Study (Relationship between OCT Coronary Plaque Morphology and Clinical Outcome) put forward the concept of High-risk plaque (HRP) and demonstrated that HRP were correlated with the high risk of major coronary events[1, 2]. HRP were defined as the presence of four simultaneous characteristics: minimum lumen area (MLA) <3.5mm2, fibrous cap thickness (FCT) <75 μm, lipid arc circumferential extension >180°, and the presence of macrophage infiltration. Early prediction of HRP formation are of great significance for the prevention and treatment of Acute Coronary Syndrome (ACS), but there are no relevant studies. Purpose To identify the risk factors related to OCT HRP in ACS and establish risk prediction model for HRPs in ACS. Methods A prospective observational cohort study was carried out on the patients with ACS from September 2019 to August 2022. A total of 169 patients were divided into OCT HRP (n=55) and OCT non-HRP (n=114) groups. Clinical information, laboratory examination and the OCT characteristics of the patients were collected. LASSO regression was used to screen variables, and multivariate logistic regression was used to establish risk prediction model. A nomogram was formulated, use the ROC curve to evaluate the discrimination of the model and the Bootstrap method to internally validate the model. Results The most frequently observed HRP characteristic was Lipid plague>180°(147 patients），followed by MLA<3.5mm2(141 patients), macrophages(127 patients), FCT<75μm(64 patients). The LASSO regression model was used to screen variables and construct an HRP risk factor model. This final model included age, BMI≥25, TC, LDL-C and Log NT-proBNP. The model is well differentiated (AUC 0.780, 95%CI 0.705-0.855) and calibrated. Decision Curve Analysis shows that the model has good net benefits. Conclusion This prediction model can accurately predict the risk of OCT HRP in patients with ACS, and is expected to assist clinicians in diagnosis and prevention of plaque stability.

246 Air pollution and coronary plaque vulnerability and instability: an optical coherence tomography study

Abstract Aims Air pollution is an emerging key player in determining the residual risk of coronary events. However, pathophysiological mechanisms linking air pollution and coronary events have been not adequately investigated. We aimed at assessing the relationship between exposure to air pollutants and mechanisms of coronary instability evaluated by optical coherence tomography (OCT) in patients with acute coronary syndrome (ACS). Methods and results ACS patients undergoing OCT imaging were retrospectively selected. Mechanism of culprit lesion instability was classified as plaque rupture (PR) or intact fibrous cap (IFC) by OCT, and the presence of macrophage infiltrates (MØI) and thin-cap fibroatheroma (TCFA) at the culprit site was also assessed. Based on each case’s home address, exposure to several pollutants was evaluated, including particulate matter 2.5 (PM2.5), particulate matter 10 (PM10), and carbon monoxide (CO). Only patients with >2 years of available data on air pollution exposure prior to ACS were enrolled. We included 126 patients [median age 67.0 years (55.5–76.0), 97 (77.0%) male]. Sixty-six patients (52.4%) had PR as mechanism of plaque instability. Patients with PR were exposed to significantly higher PM2.5 levels compared to IFC, and PM2.5 was independently associated with PR [odds ratio per unit = 1.194, 95% CI: (1.036–1.377), P = 0.015]. Moreover, exposure to higher levels of PM2.5 was independently associated with the presence of TCFA and of MØI at the culprit site. Interestingly, PM2.5, PM10, and CO levels were positively and significantly correlated with serum levels of C-reactive protein. ROC curves were constructed to assess the ability of PM2.5 to predict the presence of plaque rupture, TCFA or MØI. The AUC for PM2.5 to predict plaque rupture was 0.62 (95% CI: 0.52–0.71, P = 0.018), for TCFA was 0.71 (95% CI: 0.61–0.80, P <0.001) and for MØI was 0.80 (95% CI: 0.71–0.88, P <0.001). Using a PM2.5 cut-off value of 13.40 μg/m3, the sensitivity and specificity for MØI were 81% and 66%, respectively. Conclusions We provide novel insights into the missing link between air pollution and increased risk of coronary events. In particular, exposure to higher concentrations of air pollutants is a risk factor for vulnerable plaque features and for plaque rupture as mechanism of coronary instability mediated by systemic and local plaque inflammation. Of importance, the thresholds of air pollutants that predicted the presence of vulnerable plaque features are far lower than commonly accepted safety thresholds used to start preventive measures for public health, suggesting that further efforts are needed in order to reduce the adverse effects on the cardiovascular system.

Air Pollution and Coronary Plaque Vulnerability and Instability: An Optical Coherence Tomography Study

ObjectivesWe assessed the relationship between exposure to air pollutants and mechanisms of coronary instability evaluated by optical coherence tomography (OCT) in patients with acute coronary syndrome (ACS). BackgroundAir pollution is an emerging key player in determining the residual risk of coronary events. However, pathophysiological mechanisms linking air pollution and coronary events have been not adequately investigated. MethodsPatients with ACS undergoing OCT imaging were retrospectively selected. Mechanism of culprit lesion instability was classified as plaque rupture (PR) or intact fibrous cap (IFC) by OCT, and the presence of macrophage infiltrates (MØI) and thin-cap fibroatheroma (TCFA) at the culprit site was also assessed. Based on each case’s home address, exposure to several pollutants was evaluated, including particulate matter 2.5 (PM2.5), PM10, and carbon monoxide (CO). Only patients with >2 years of available data on air pollution exposure prior to ACS were enrolled. ResultsWe included 126 patients (median age: 67.0 years of age; IQR: 55.5-76.0; 97 male patients [77.0%]). Sixty-six patients (52.4%) had PR as the mechanism of plaque instability. Patients with PR were exposed to significantly higher PM2.5 levels than to IFC, and PM2.5 was independently associated with PR (odds ratio: 1.194; 95% CI: 1.036 to 1.377; P = 0.015). Moreover, exposure to higher levels of PM2.5 was independently associated with the presence of TCFA and of MØI at the culprit site. Interestingly, PM2.5, PM10, and Co levels were positively and significantly correlated with serum levels of C-reactive protein. ConclusionsWe provide novel insights into the missing link between air pollution and increased risk of coronary events. In particular, exposure to higher concentrations of air pollutants is associated with the presence of vulnerable plaque features and with plaque rupture as a mechanism of coronary instability. An enhanced systemic and plaque inflammatory activation may explain these findings.

Long-term exposure to ambient air pollution portends a higher risk of coronary plaque vulnerability and instability in patients with acute coronary syndrome: an optical coherence tomography study

Abstract Background Air pollution is an emerging key player in determining the residual risk of coronary events. However, pathophysiological mechanisms linking air pollution and coronary events have been not adequately investigated. Purpose We assessed the relationship between exposure to air pollutants and mechanisms of coronary instability evaluated by optical coherence tomography (OCT) in patients with acute coronary syndrome (ACS). Methods ACS patients undergoing OCT imaging were retrospectively selected. Mechanism of culprit lesion instability was classified as plaque rupture (PR) or intact fibrous cap (IFC) by OCT, and the presence of macrophage infiltrates (MØI) and thin-cap fibroatheroma (TCFA) at the culprit site was also assessed. Based on each case's home address, exposure to several pollutants was evaluated, including particulate matter 2.5 (PM2.5), particulate matter 10 (PM10), and carbon monoxide (CO). Only patients with >2 years of available data on air pollution exposure prior to ACS were enrolled. Results We included 136 patients [median age 67.0 years (56.2–76.0), 104 (76.5%) male]. Sixty-six patients (48.5%) had PR as mechanism of plaque instability. Patients with PR were exposed to significantly higher PM2.5 levels compared to IFC, and PM2.5 was an independent predictor for PR (OR=1.133, 95% CI [1.020–1.258], p=0.019). Moreover, exposure to higher levels of PM2.5, PM10 and CO was an independent predictor for the presence of TCFA, while PM2.5 and CO levels predicted the presence of MØI. Interestingly, PM2.5, PM10 and CO levels were positively and significantly correlated with serum levels of C-reactive protein. ROC curves were constructed to assess the ability of PM2.5 to predict the presence of plaque rupture, TCFA or MØI. The AUC for PM2.5 to predict plaque rupture was 0.62 (95% CI: 0.52–0.71, p=0.018), for TCFA was 0.71 (95% CI: 0.61–0.80, p<0.001) and for MØI was 0.80 (95% CI: 0.71–0.88, p<0.001). Using a PM2.5 cut-off value of 13.40 μg/m3, the sensitivity and specificity for MØI were 81% and 66%, respectively. Conclusions We provide novel insights into the missing link between air pollution and increased risk of coronary events. In particular, exposure to higher concentrations of air pollutants is a risk factor for vulnerable plaque features and for plaque rupture as mechanism of coronary instability mediated by systemic and local plaque inflammation. Of importance, the thresholds of air pollutants that predicted the presence of vulnerable plaque features are far lower than commonly accepted safety thresholds used to start preventive measures for public health, suggesting that further efforts are needed in order to reduce the adverse effects on the cardiovascular system. Funding Acknowledgement Type of funding sources: None. Air pollutants exposure and OCT featuresROC curve analysis

The Usefulness of CD34, PCNA Immunoreactivity, and Histopathological Findings for Prediction of Pain Persistence After the Removal of Endometrioma.

Endometriosis is an estrogen-dependent inflammatory disease that causes infertility and chronic pelvic pain. Ovarian endometrioma is the most common form of endometriosis, and conservative surgery is the main preferred therapeutic approach for endometrioma-associated symptoms. The aim of this study was to investigate the persistence of cyclic and noncyclic pelvic pain (NCPP) after endometrioma excision and their relationship to clinical and histopathological findings. In this prospective observational study, 41 symptomatic patients were evaluated for the presence of pain symptoms 3 to 6 months after endometrioma excision. Tissue specimens of endometrioma were collected during the operation and embedded in paraffin. The persistence of pain was 41.4%. Surgical excision of endometrioma significantly decreased NCPP and dysmenorrhea, but not dyspareunia ( P < .0001, P = .0001, and P = .25, respectively). Histopathological changes, including depth of endometriosis penetration into the cyst wall, the presence of macrophage infiltration, and vascularity of endometrioma cyst walls were significantly higher in patients with pain persistence than in patients without pain persistence ( P = .0034, P = .0042, and P = .0007, respectively). Moreover, proliferating cell nuclear antigen (PCNA) and CD34 immunoreactivity in both glandular and stromal cells and vascular endothelium were significantly higher in patients with pain persistence ( P = .0079 and P = .0025, respectively). Additionally, these histopathological changes and PCNA and CD34 immunoreactivity were significantly correlated with the persistence of NCPP and dysmenorrhea. The discovered differences in patients with endometrioma with or without pain persistence may indicate a possible relationship between endometrioma-associated pain and histopathological variability of endometrioma.

POLYCYSTIC OVARY SYNDROME IN NILE TILAPIA, Oreochromis niloticus

This study presented a case report of a female of Oreochromis niloticus in the reproductive age. In the clinical analysis, the animal showed intense abdominal distension, severe cachexia, retraction of the eyeball and lethargic behavior. At the necropsy, it was observed the presence of neoplastic mass in the peritoneal cavity which presented smooth surface, circular appearance, soft consistency and reddish-blackened focal regions. There was the formation of multiple cysts, which presented a yellowish-green liquid content in the cut. In the histopathological examination, multiple dilatations were observed, filled with amorphous eosinophilic material with a delicate fibrocolagenous wall, as well as detachment of the granulosa and theca cells. The presence of macrophage infiltrates with hemosiderin pigments was also observed. The macroscopic and microscopic findings confirm the diagnosis of polycystic ovarian syndrome; however the causes of this cystic disease were not understood.

A Novel Modality for Functional Imaging in Acute Intervertebral Disk Herniation via Tracking Leukocyte Infiltration.

Inflammation plays a key role in the progression of intervertebral disk (IVD) herniation and associated low back pain. However, real-time spatial diagnosis of inflammation associated with acute disk herniation has not been investigated. We sought to detect local neutrophil and macrophage infiltration near disk herniation via the formyl peptide receptor 1 (FPR1)-mediated molecular imaging in a disk puncture mouse model to elucidate pathophysiological process of disk herniation. Disk herniation was induced in mouse with an established needle puncture procedure. Degenerative change of disk and infiltration of neutrophils and macrophages were detected with Safranin-O, hematoxylin and eosin (H&E), and immunohistochemical staining after injury. FPR1-specific imaging probes cFLFLF-PEG-Cy7 and [99mTc]HYNIC-PEG-cFLFLF were administered systemically to sham and disk injury mice. Leukocyte infiltration was tracked by in vivo near-infrared fluorescence (NIRF) and single-photon emission tomography (SPECT) imaging. The peptide-receptor binding specificity was further investigated with FPR1-/- mice via ex vivo NIRF scan and in vitro binding assays. Safranin-O staining exhibited disorganized disk structure and loss of proteoglycan after puncture. Massive inflammatory cells were observed in the anterior region of punctured annulus in the injury group. The majority of neutrophils were detected at 1 through 3days, while infiltration of macrophages appeared the most at 7days after injury. NIRF and SPECT images revealed preferential accumulation of cFLFLF probes in herniation site in wild-type mice but not in FPR1-/- mice. Binding of the cFLFLF peptide to FPR1 was also observed in RAW 267.4 cells and macrophages isolated from wild-type mice, whereas much less signal was observed in macrophages from FPR1-/- mice. The presence of macrophage infiltration was also detected in human-herniated disk samples by immunohistochemistry. For the first time, leukocyte infiltration around acute disk herniation site was detected directly and non-invasively in a timely fashion using FPR1-targeted molecular imaging modalities. Such functional imaging of disk herniation via infiltrated leukocytes would advance the understanding of etiology and facilitate drug delivery and treatment monitoring of disk herniation.

Psoriatic Arthritis Complicating Systemic Sclerosis: Possible Involvement of M2 Macrophages.

Dear Editor: Psoriatic arthritis (PsA) is a seronegative inflammatory arthritis that occurs in the presence of psoriasis. The synovial macrophages are a major source of proinflammatory cytokines1. The subset of macrophages that expresses alternatively activated macrophages (M2 macrophages) is usually greater in number in PsA synovitis than in rheumatoid arthritis synovitis2. Systemic sclerosis (SSc) is a rheumatological disorder characterized by excessive fibrosis and microvascular damage of the skin and various internal organs. The presence of macrophage infiltrates and increased numbers of M2 macrophages in fibrotic areas have been reported3. A 44-year-old Japanese man developed scaly erythema that had been present on the trunk and lower and upper extremities for 40 years. A primary care doctor had diagnosed his condition as psoriasis. His previous treatments included topical corticosteroid therapy, topical psoralen ultraviolet-A therapy, or oral cyclosporin. Sacroiliitis was also associated with the skin symptoms. For the previous 4 years, the scaly erythema had gradually improved but was then complicated by sclerodactylia. On examination, a high anti-nuclear antibody (ANA) titer with homogeneous, speckled, and nucleolar patterns (×640) was present. Detailed analysis of the ANA revealed that there was a significant increase in anti-topoisomerase I antibody (152 U/ml). Rheumatoid factor was negative. From these results, the presumptive diagnosis was SSc complicated by PsA, and the patient was admitted to our hospital. Psoriatic plaque was present on the elbows of the patient (Fig. 1A). The modified Rodnan total skin thickness score value of 22 was used to grade the degree of skin sclerosis (Fig. 1B). The levels of T helper 2 cytokines, such as interleukin (IL)-4 (17.0 pg/ml) and transforming growth factor (TGF)-β1 (15.1 ng/ml), were elevated. The serum Krebs von den Lungen-6 (1,182 U/ml) and surfactant protein D (226 ng/ml) levels were elevated, and high-resolution computed tomography revealed the presence of a bilateral consolidation of both lower lobes with peripheral ground glass opacity. Skin biopsies from the elbow and the forearm revealed the presence of markedly elongated rete ridges with parakeratosis (Fig. 1C), and sclerotic change that ascended from the lower dermis (Fig. 1D). We also performed immunostaining for CD68 (Fig. 1E, F) and CD163 (Fig. 1G, H) in lesional skin biopsy samples. Subequal infiltrated dermal cells expressed CD68, which suggested that macrophages infiltrated both types of samples of lesional skin. Furthermore, the numbers of CD163-positive cells were increased in lesional skin from SSc. This result suggests that M2 macrophages were increased in lesional skin from SSc compared with lesional skin from PsA (Fig. 1E~H). Fig. 1 Clinical and histopathological manifestations in the patient. (A) Psoriatic skin lesion affecting the elbow. (B) Widespread skin thickening, progressing from the fingers to the trunk. (C) The skin biopsy specimen from the elbow has characteristics consistent ... Polarized macrophages have been broadly classified into two groups: M1 and M2 macrophages. Tissue macrophages can exist in different activation states. They can be proinflammatory macrophages (M1; activated by interferon-γ or lipopolysaccharide) or anti-inflammatory macrophages (M2; activated by TGF-β or IL-4)4. They participate in tissue remodeling, immune modulation, parasite clearance, and tumor progression5. In this patient, M2 macrophages may be one of the key regulating cell types involved in the clinical manifestations. However, further investigations are needed for elucidating the involvement of M2 macrophages in skin disorders.

Adipocyte Apoptosis, a Link between Obesity, Insulin Resistance, and Hepatic Steatosis

Adipocyte death has been reported in both obese humans and rodents. However, its role in metabolic disorders, including insulin resistance, hepatic steatosis, and inflammation associated with obesity has not been studied. We now show using real-time reverse transcription-PCR arrays that adipose tissue of obese mice display a pro-apoptotic phenotype. Moreover, caspase activation and adipocyte apoptosis were markedly increased in adipose tissue from both mice with diet-induced obesity and obese humans. These changes were associated with activation of both the extrinsic, death receptor-mediated, and intrinsic, mitochondrial-mediated pathways of apoptosis. Genetic inactivation of Bid, a key pro-apoptotic molecule that serves as a link between these two cell death pathways, significantly reduced caspase activation, adipocyte apoptosis, prevented adipose tissue macrophage infiltration, and protected against the development of systemic insulin resistance and hepatic steatosis independent of body weight. These data strongly suggest that adipocyte apoptosis is a key initial event that contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis associated with obesity in both mice and humans. Inhibition of adipocyte apoptosis may be a new therapeutic strategy for the treatment of obesity-associated metabolic complications.

Apoptosis and macrophage infiltration occur simultaneously and present a potential sign of muscle injury in skeletal muscle of nutritionally compromised, early post-hatch turkeys

Physical stress and malnutrition may cause elimination of myonuclei and produce inflammatory response in muscle. The objective of this study was to histochemically determine the association of apoptosis and/or macrophage infiltration with changes in muscle satellite cell mitotic activity in pectoralis thoracicus muscle of early post-hatch turkey toms. Feed-deprived birds and birds provided with three different levels of crude protein and amino acids (0.88 NRC, 1.00 NRC, and 1.12 NRC) were used in this model. The number of apoptotic nuclei was significantly elevated (P<0.05) and presence of macrophage infiltration was readily detectable in feed-deprived and 0.88 NRC treatment groups 72 h and 96 h post-hatch suggesting potential muscle injury and/or muscle remodeling. The number of apoptotic nuclei was the same (P>0.05), and there was no detectable macrophage infiltration present in birds placed on 1.00 NRC and 1.12 NRC diet 72 h, 96 h, and 120 h post-hatch. At 120 h post-hatch, feed-deprived and 0.88 NRC birds were characterized by no detectable levels of macrophage infiltration and a significant drop (P<0.05) in apoptotic nuclei. Understanding mechanisms that correlate early nutrition with skeletal muscle growth and development may present a useful tool in optimizing muscle health and improving meat quality and yield.

Decreased number of activated macrophages in gallbladder muscle layer of cholesterol gallstone patients following ursodeoxycholic acid

We recently reported that, in symptomatic cholesterol gallstone patients, ursodeoxycholic acid (UDCA) improves gallbladder (GB) muscle contractility and decreases the biochemical parameters of oxidative stress and inflammation.1 UDCA also antagonises...