Tissue characteristics of residual lesion in patients with acute coronary syndrome caused by plaque rupture versus plaque erosion: a single-center, retrospective, observational study.

Patients with acute coronary syndrome (ACS), frequently caused by plaque rupture (PR), often have vulnerable plaques in residual lesions as well as in culprit lesions. However, whether this occurs in patients with plaque erosion (PE) as well is unknown. We retrospectively analyzed the data of 88 patients with ACS who underwent both optimal coherence tomography (OCT) and intravascular ultrasound (IVUS). Based on plaque morphology of the culprit lesions identified using OCT, patients were classified into PE (n=23) and PR (n=35) groups. The tissue characteristics of residual lesions evaluated using integrated backscatter IVUS were compared between both groups after percutaneous coronary intervention. The PE group had a significantly lower percent lipid volume and a higher percent fibrous volume than the PR group (35.0±17.8% vs 49.2±13.4%, p<0.001; 63.2±17.1% vs 50.3±13.1%, p=0.002, respectively). Receiver operating characteristic curve analysis revealed that percent lipid volume in the residual lesions was a significant discriminant factor in estimating the plaque morphology of the culprit lesion (optimal cut-off value, <43.5%; sensitivity and specificity values were 73.9% and 68.6%, respectively). In conclusion, patients with PE had a significantly lower percent lipid volume and a significantly higher percent fibrous volume in the residual lesions than those with PR, suggesting that the nature of coronary plaques in patients with PE is different from that of those with PR.

Excessive accumulation of epicardial adipose tissue promotes microvascular obstruction formation after myocardial ischemia/reperfusion through modulating macrophages polarization.

BACKGROUND: Owing to its unique location and multifaceted metabolic functions, epicardial adipose tissue (EAT) is gradually emerging as a new metabolic target for coronary artery disease risk stratification. Microvascular obstruction (MVO) has been recognized as an independent risk factor for unfavorable prognosis in acute myocardial infarction patients. However, the concrete role of EAT in the pathogenesis of MVO formation in individuals with ST-segment elevation myocardial infarction (STEMI) remains unclear. The objective of the study is to evaluate the correlation between EAT accumulation and MVO formation measured by cardiac magnetic resonance (CMR) in STEMI patients and clarify the underlying mechanisms involved in this relationship. METHODS: Firstly, we utilized CMR technique to explore the association of EAT distribution and quantity with MVO formation in patients with STEMI. Then we utilized a mouse model with EAT depletion to explore how EAT affected MVO formation under the circumstances of myocardial ischemia/reperfusion (I/R) injury. We further investigated the immunomodulatory effect of EAT on macrophages through co-culture experiments. Finally, we searched for new therapeutic strategies targeting EAT to prevent MVO formation. RESULTS: The increase of left atrioventricular EAT mass index was independently associated with MVO formation. We also found that increased circulating levels of DPP4 and high DPP4 activity seemed to be associated with EAT increase. EAT accumulation acted as a pro-inflammatory mediator boosting the transition of macrophages towards inflammatory phenotype in myocardial I/R injury through secreting inflammatory EVs. Furthermore, our study declared the potential therapeutic effects of GLP-1 receptor agonist and GLP-1/GLP-2 receptor dual agonist for MVO prevention were at least partially ascribed to its impact on EAT modulation. CONCLUSIONS: Our work for the first time demonstrated that excessive accumulation of EAT promoted MVO formation by promoting the polarization state of cardiac macrophages towards an inflammatory phenotype. Furthermore, this study identified a very promising therapeutic strategy, GLP-1/GLP-2 receptor dual agonist, targeting EAT for MVO prevention following myocardial I/R injury.

Quantification of cardiac capillarization in basement-membrane-immunostained myocardial slices using Segment Anything Model.

Decreased myocardial capillary density has been reported as an important histopathological feature associated with various heart disorders. Quantitative assessment of cardiac capillarization typically involves double immunostaining of cardiomyocytes (CMs) and capillaries in myocardial slices. In contrast, single immunostaining of basement membrane protein is a straightforward approach to simultaneously label CMs and capillaries, presenting fewer challenges in background staining. However, subsequent image analysis always requires expertise and laborious manual work to identify and segment CMs/capillaries. Here, we developed an image analysis tool, AutoQC, for automatic identification and segmentation of CMs and capillaries in immunofluorescence images of basement membrane. Commonly used capillarization-related measurements can be derived from segmentation results. By leveraging the power of a pre-trained segmentation model (Segment Anything Model, SAM) via prompt engineering, the training of AutoQC required only a small dataset with bounding box annotations instead of pixel-wise annotations. AutoQC outperformed SAM (without prompt engineering) and YOLOv8-Seg, a state-of-the-art instance segmentation model, in both instance segmentation and capillarization assessment. Thus, AutoQC, featuring a weakly supervised algorithm, enables automatic segmentation and high-throughput, high-accuracy capillarization assessment in basement-membrane-immunostained myocardial slices. This approach reduces the training workload and eliminates the need for manual image analysis once AutoQC is trained.

Differential responses to thrombospondin-1 and PDGF-BB in smooth muscle cells from atherosclerotic coronary arteries and internal thoracic arteries.

Atherosclerosis is rare in internal thoracic arteries (ITA) even in patients with severe atherosclerotic coronary artery (ACA) disease. To explore cellular differences, ITA SMC from 3 distinct donors and ACA SMC from 3 distinct donors were grown to sub-confluence and growth arrested for 48 h. Proliferation and thrombospondin-1 (TSP1) production were determined using standard techniques. ITA SMC were larger, grew more slowly and survived more passages than ACA SMC. ACA SMC had a more pronounced proliferative response to 10% serum than ITA SMC. Both ACA SMC and ITA SMC proliferated in response to exogenous TSP1 (12.5 µg/ml and 25 µg/ml) and platelet derived growth factor-BB (PDGF-BB; 20 ng/ml) but TSP1- and PDGF-BB-induced proliferation were partially inhibited by anti-TSP1 antibody A4.1, microRNA-21(miR-21)-3p inhibitors and miR-21-5p inhibitors in each of the 3 ACA SMC lines, but not in any of the ITA SMC lines. PDGF-BB stimulated TSP1 production in ACA SMC but not in ITA SMC but there was no increase in TSP1 levels in conditioned media in either SMC type. In summary, there are significant differences in morphology, proliferative capacity and in responses to TSP1 and PDGF-BB in SMC derived from ITA compared to SMC derived from ACA.

Low HDL-C/ApoA-I index is associated with cardiometabolic risk factors and coronary artery calcium: a sub-analysis of the genetics of atherosclerotic disease (GEA) study.

BACKGROUND: The high-density lipoprotein cholesterol to apolipoprotein A-I index (HDL-C/ApoA-I) may be practical and useful in clinical practice as a marker of atherosclerosis. This study aimed to investigate the association between the HDL-C/ApoA-I index with cardiometabolic risk factors and subclinical atherosclerosis. METHODS: In this cross-sectional sub-analysis of the GEA study, 1,363 individuals, women (51.3%) and men (48.7%) between 20 and 75 years old, without coronary heart disease or diabetes mellitus were included. We defined an adverse cardiometabolic profile as excess adipose tissue metrics, non-alcoholic liver fat measured by non-contrasted tomography, metabolic syndrome, dyslipidemias, and insulin resistance. The population was stratified by quartiles of the HDL-C/Apo-AI index, and its dose-relationship associations were analysed using Tobit regression, binomial, and multinomial logistic regression analysis. RESULTS: Body mass index, visceral and pericardial fat, metabolic syndrome, fatty liver, high blood pressure, and CAC were inversely associated with the HDL-C/ApoA-I index. The CAC > 0 prevalence was higher in quartile 1 (29.2%) than in the last quartile (22%) of HDL-C/ApoA-I index (p = 0.035). The probability of having CAC > 0 was higher when the HDL-C/ApoA-I index was less than 0.28 (p < 0.001). This association was independent of classical coronary risk factors, visceral and pericardial fat measurements. CONCLUSION: The HDL-C/ApoA-I index is inversely associated with an adverse cardiometabolic profile and CAC score, making it a potentially useful and practical biomarker of coronary atherosclerosis. Overall, these findings suggest that the HDL-C/ApoA-I index could be useful for evaluating the probability of having higher cardiometabolic risk factors and subclinical atherosclerosis in adults without CAD.

[Correlation between coronary artery tortuosity and poor prognosis in patients with septal hypertrophic cardiomyopathy].

Objective: To investigate the incidence of coronary artery tortuosity and its correlation with poor prognosis in patients with septal hypertrophic cardiomyopathy (HCM). Methods: This was a retrospective cohort study. Patients with septal HCM who were hospitalized in Fuwai Central China Cardiovascular Hospital and Zhengzhou University People's Hospital between December 1, 2017 and June 10, 2021 were selected. Non-HCM patients were matched by gender, age, and hypertension as control group. Septal HCM was divided into two groups based on the presence or absence of coronary artery tortuosity. Clinical baseline data and coronary angiography findings were compared using a multifactorial logistic analysis of the risk factors for coronary artery tortuosity. Patients were followed up until July 1, 2022, with the primary outcome being the composite endpoint of malignant arrhythmia, ischemic stroke and all-cause death. Incidence densities were compared between the coronary artery tortuosity and non-coronary artery tortuosity groups of septal HCM patients. The Cox risk-ratio model was used to analyze risk factors for primary outcomes in septal HCM patients. Results: There were 156 patients in the septal HCM group and 156 patients in the control group, both aged (57.0±11.4) years, and 75 (48.1%) were female. The incidence of coronary artery tortuosity was significantly higher in the septal HCM group than in the control group (63.5% vs. 36.5%, P<0.01), and the coronary artery tortuosity score was also higher in the septal HCM group than in the control group (P<0.01). Multiple logistic regression analysis showed that septal HCM was a risk factor for coronary artery tortuosity (OR=3.27, 95%CI: 2.02-5.29, P<0.01). In the septal HCM patients, after (2.5±1.2) years of follow-up, the incidence density of primary outcome was significantly higher in the coronary artery tortuosity group than in the non-coronary artery tortuosity group (P=0.02), while each on-point in coronary artery tortuosity score increased the risk of primary outcome by 53% for septal HCM patients (HR=1.53, 95%CI: 1.26-1.86, P<0.01). Conclusions: Patients with septal HCM are more prone to suffer coronary artery tortuosity and suffer from it to a greater extent. Coronary artery tortuosity is an important risk factor for adverse events in patients with septal HCM.

Evaluating the Association between Anomalous Aortic Origin of the Right Coronary Artery from the Left Sinus with Interarterial Course at Coronary CT Angiography and Sudden Cardiac Death.

Purpose To investigate the association between the anomalous aortic origin of the right coronary artery (R-AAOCA) from the left coronary sinus with interarterial course (IAC) found at coronary CT angiography and sudden cardiac death using a large data set from five university hospitals. Materials and Methods From a total of 89 314 CCTA scans (January 2009 to December 2016) that were retrospectively collected, 316 patients with R-AAOCA from the left sinus with IAC were retrospectively collected. After excluding patients with less than 2 years of follow-up, patients who had already undergone cardiovascular surgery or intervention, and patients with arrhythmia or heart failure before undergoing coronary CT angiography, 224 patients were analyzed. Follow-up was terminated upon the occurrence of major adverse cardiovascular events (MACE). Logistic regression was used to identify clinical and radiologic information as independent predictors of MACE. Results The period prevalence of R-AAOCA from the left sinus with IAC was 0.354%. The mean age was 62.03 years, with a male-to-female ratio of 182:134. During follow-up, 19 of 224 patients (8.5%) experienced MACE, but none had sudden cardiac death. Of these cases, only seven (3.13%) were suspected of being due to R-AAOCA from the left sinus with IAC and all of them had unstable angina. Coronary artery disease was significantly associated with MACE (P < .001), while no significant correlation was observed with radiologic features. Conclusion Sudden cardiac death was not associated with R-AAOCA from the left sinus with IAC found at coronary CT angiography. The occurrence of MACE was low, with coronary artery disease being the sole significant predictor of a patient's prognosis. Keywords: Anomalous Aortic Origin of the Right Coronary Artery, Left Coronary Sinus with Interarterial Course, Coronary CT Angiography, Sudden Cardiac Death Supplemental material is available for this article. © RSNA, 2024.

Improved Detection of Small and Low-Density Plaques in Virtual Noncontrast Imaging-based Calcium Scoring at Photon-Counting Detector CT.

Purpose To investigate the impact of plaque size and density on virtual noncontrast (VNC)-based coronary artery calcium scoring (CACS) using photon-counting detector CT and to provide safety net reconstructions for improved detection of subtle plaques in patients whose VNC-based CACS would otherwise be erroneously zero when compared with true noncontrast (TNC)-based CACS. Materials and Methods In this prospective study, CACS was evaluated in a phantom containing calcifications with different diameters (5, 3, and 1 mm) and densities (800, 400, and 200 mg/cm3) and in participants who underwent TNC and contrast-enhanced cardiac photon-counting detector CT (July 2021-March 2022). VNC images were reconstructed at different virtual monoenergetic imaging (55-80 keV) and quantum iterative reconstruction (QIR) levels (QIR,1-4). TNC scans at 70 keV with QIR off served as the reference standard. In vitro CACS was analyzed using standard settings (3.0-mm sections, kernel Qr36, 130-HU threshold). Calcification detectability and CACS of small and low-density plaques were also evaluated using 1.0-mm sections, kernel Qr44, and 120- or 110-HU thresholds. Safety net reconstructions were defined based on background Agatston scores and evaluated in vivo in TNC plaques initially nondetectable using standard VNC reconstructions. Results The in vivo cohort included 63 participants (57.8 years ± 15.5 [SD]; 37 [59%] male, 26 [41%] female). Correlation and agreement between standard CACSVNC and CACSTNC were higher in large- and medium-sized and high- and medium-density than in low-density plaques (in vitro: intraclass correlation coefficient [ICC] ≥ 0.90; r > 0.9 vs ICC = 0.20-0.48; r = 0.5-0.6). Small plaques were not detectable using standard VNC reconstructions. Calcification detectability was highest using 1.0-mm sections, kernel Qr44, 120- and 110-HU thresholds, and QIR level of 2 or less VNC reconstructions. Compared with standard VNC, using safety net reconstructions (55 keV, QIR 2, 110-HU threshold) for in vivo subtle plaque detection led to higher detection (increased by 89% [50 of 56]) and improved correlation and agreement of CACSVNC with CACSTNC (in vivo: ICC = 0.51-0.61; r = 0.6). Conclusion Compared with TNC-based calcium scoring, VNC-based calcium scoring was limited for small and low-density plaques but improved using safety net reconstructions, which may be particularly useful in patients with low calcium scores who would otherwise be treated based on potentially false-negative results. Keywords: Coronary Artery Calcium CT, Photon-Counting Detector CT, Virtual Noncontrast, Plaque Size, Plaque Density Supplemental material is available for this article. © RSNA, 2024.

[The association of cholesterol crystals and non-culprit plaque characteristics in AMI patients: an OCT study].

Objective: To analyze plaque characteristics of non-culprit coronary lesions with cholesterol crystals in patients with acute myocardial infarction(AMI) by using optical coherence tomography(OCT). We also investigated the potential association between cholesterol crystals with plaque rupture and healed plaque at non-culprit segment. Methods: This study was a retrospective cohort study. Between January 2017 and December 2017, patients with AMI who underwent 3-vessel OCT imaging were included in this study. Patients were divided into two groups according to the presence or absence of cholesterol crystals at the non-culprit lesions. All patients underwent coronary angiography and OCT examination, and non-culprit plaque characteristics were compared between the two groups. The generalized estimating equation log-binomial multirariate regression model was used to assess the relationship between non-culprit lesions with cholesterol crystals and plaque rupture and plaque healing. The follow-up data collection ended in October 2023. Kaplan-Meier survival curves were plotted, and log-rank tests were used to compare the cumulative incidence of major adverse cardiovascular events between the two groups. Results: A total of 173 AMI patients were included (aged (56.8±11.6) years; 124 men (71.7%)). Among 710 non-culprit lesions identified by OCT, there were 102 (14.4%) in cholesterol crystals group and 608 (85.6%) in non-cholesterol crystals group. Compared with non-culprit lesions without cholesterol crystals, those with cholesterol crystals had smaller minimum lumen diameter, severer diameter stenosis, and longer lesion length (all P<0.01). The prevalence of plaque rupture (17.6% (18/102) vs. 4.9% (30/608), P=0.001) and thin-cap fibroatheroma (31.4% (32/102) vs. 11.5% (70/608), P<0.01) was higher in the cholesterol crystals groups than in the non-cholesterol crystals group. In addition, vulnerable plaque characteristics such as (44.1% (45/102) vs. 25.8% (157/608), P<0.01), macrophages were more frequently observed in non-culprit lesions with cholesterol crystals. The generalized estimating equation log-binomial multivariate regression analyses showed that non-culprit cholesterol crystals were positively correlated with healed plaque (OR=1.583, 95%CI: 1.004-2.495, P=0.048). Conversely, cholesterol crystals were not associated with plaque rupture (OR=1.632, 95%CI: 0.745-3.576, P=0.221). The follow-up time was 2 142 (1 880, 2 198) days. Non-culprit cholesterol crystals were not related to the major adverse cardiovascular events in patients with AMI (log-rank P=0.558). Conclusions: Among AMI patients, non-culprit lesions with cholesterol crystals presented with severer luminal stenosis and increased plaque vulnerability. The presence of non-culprit cholesterol crystals was associated with rather than plaque rupture.

[Association between body composition and coronary artery calcification in patients with chronic kidney disease].

Objective: To investigate the association between body composition and coronary artery calcification in patients with chronic kidney disease (CKD). Methods: This cross-sectional study enrolled patients with CKD hospitalized from May 2019 to April 2022 at Sun Yat-sen Memorial Hospital, Guangzhou, China. Skeletal muscle mass index and visceral fat area were measured by bioelectrical impedance analysis. Coronary artery calcification was assessed by computed tomography. Patients were divided into coronary artery calcification group and non-coronary artery calcification group according to the incidence of coronary artery calcification. Patients were categorized into tertile groups according to their skeletal muscle mass index and visceral fat area levels ranging from the lowest to the highest levels (T1 to T3). We defined skeletal muscle mass index≤30.4% as low muscle mass and visceral fat area≥80.6 cm2 as high visceral fat based on the results of the restricted cubic spline graph. All individuals were divided into 4 phenotypes: normal body composition, low muscle mass, high visceral fat, and low muscle mass with high visceral fat. Spearman correlation analysis and logistic regression analysis were used to assess the association between skeletal muscle mass index, visceral fat area and coronary artery calcification. Results: A total of 107 patients with CKD were enrolled, with an age of (60.0±14.1) years, including 41 female patients (38.3%). Patients of coronary artery calcification group had lower skeletal muscle mass index ((32.0±4.8) vs. (34.3±4.8), P=0.016) and higher visceral fat area ((70.8±32.6) cm2 vs. (47.9±23.8) cm2, P<0.001) than those of non-coronary artery calcification group. Patients in the T3 group of skeletal muscle mass index had a lower prevalence of coronary artery calcification (17 (48.6%) vs. 28 (77.8%)) and a lower coronary artery calcification score (0.5 (0, 124.0) vs. 12.0 (0.3, 131.0)) than those in the T1 group (P<0.05). Similarly, patients in the T1 group of visceral fat area had a lower prevalence of coronary artery calcification (14 (40.0%) vs. 29 (80.6%)) and a lower coronary artery calcification score (0 (0, 3.0) vs. 37.0 (2.0, 131.0)) than those in the T3 group (P<0.05). Likewise, patients with both low muscle mass and low muscle mass with high visceral fat had a higher prevalence of coronary artery calcification (11(78.6%) vs. 33 (47.8%); 15 (83.3%) vs. 33 (47.8%)) and a higher coronary artery calcification score (31.1 (0.8, 175.8) vs. 0 (0, 16.4); 27.6 (6.4, 211.4) vs. 0 (0, 16.4)) than those with normal body composition (P<0.05). Spearman correlation analysis showed that skeletal muscle mass index was inversely correlated with coronary artery calcification score (r=-0.212, P=0.028), and visceral fat area was positively correlated with coronary artery calcification score (r=0.408, P<0.001). Multivariate logistic regression analysis showed that increased skeletal muscle mass index was inversely associated with coronary artery calcification prevalence (T2: OR=0.208, 95%CI: 0.056-0.770, P=0.019; T3: OR=0.195, 95%CI: 0.043-0.887, P=0.034), and reduced visceral fat area was inversely associated with coronary artery calcification prevalence (T1: OR=0.256, 95%CI: 0.071-0.923, P=0.037; T2: OR=0.263, 95%CI: 0.078-0.888, P=0.031). Consistently, both low muscle mass and low muscle mass with high visceral fat were associated with coronary artery calcification prevalence (OR=6.616, 95%CI: 1.383-31.656, P=0.018; OR=5.548, 95%CI: 1.062-28.973, P=0.042). Conclusion: Reduced skeletal muscle mass index and increased visceral fat area are significantly associated with both the prevalence and severity of coronary artery calcification in patients with CKD.

Risk factors and major adverse cardiovascular events of isolated coronary artery ectasia: An observational study.

To evaluate the cardiac index and major adverse cardiovascular events (MACE) events between isolated coronary artery ectasia (CAE) and control groups over 1 year period from diagnosis. A total of 18 patients who were diagnosed with isolated CAE in the Second Hospital of Hebei Medical University from December 2020 to December 2021 were included in CAE group. About 36 patients with non-obstructive coronary artery lesions were included in the control group. All patients in 2 groups completed dobutamine stress echocardiography (DSE) during hospitalization. The chamber size, wall thickness, left ventricular ejection fraction, and left ventricular diastolic function indicators (including E/A ratio, e', and E/e' ratio) were measured. MACE and all-cause death were measured during follow-up after discharge. Interventricular septum thickness (IVSd), left ventricular posterior wall (LVPW) thickness in diastole and E/e' in CAE group were significantly higher than control group (P < .05). No significant differences were found in prognosis including angina, myocardial ischemia (MI), patient readmission and cardiovascular death (P > .05). In CAE group, coronary angiography showed dilation of left anterior descending (LAD) in 1 case, left circumflex (LCX) in 3 cases and right coronary artery (RCA) in 14 cases. Multivariate logistic regression analysis showed that BMI and IVSd were independent risk factors for CAE. IVSd, LVPW thickness in diastole and E/e' in CAE group were significantly higher than control group. BMI and IVSd were independent risk factors for isolated CAE, and had a good predictive value for isolated CAE.

Congenital Coronary Blood Vessel Anomalies: Animal Models and the Integration of Developmental Mechanisms.

Coronary blood vessels are in charge of sustaining cardiac homeostasis. It is thus logical that coronary congenital anomalies (CCA) directly or indirectly associate with multiple cardiac conditions, including sudden death. The coronary vascular system is a sophisticated, highly patterned anatomical entity, and therefore a wide range of congenital malformations of the coronary vasculature have been described. Despite the clinical interest of CCA, very few attempts have been made to relate specific embryonic developmental mechanisms to the congenital anomalies of these blood vessels. This is so because developmental data on the morphogenesis of the coronary vascular system derive from complex studies carried out in animals (mostly transgenic mice), and are not often accessible to the clinician, who, in turn, possesses essential information on the significance of CCA. During the last decade, advances in our understanding of normal embryonic development of coronary blood vessels have provided insight into the cellular and molecular mechanisms underlying coronary arteries anomalies. These findings are the base for our attempt to offer plausible embryological explanations to a variety of CCA as based on the analysis of multiple animal models for the study of cardiac embryogenesis, and present them in an organized manner, offering to the reader developmental mechanistic explanations for the pathogenesis of these anomalies.

CD163+ Macrophages Induce Endothelial-to-Mesenchymal Transition in Atheroma.

BACKGROUND: Cell phenotype switching is increasingly being recognized in atherosclerosis. However, our understanding of the exact stimuli for such cellular transformations and their significance for human atherosclerosis is still evolving. Intraplaque hemorrhage is thought to be a major contributor to plaque progression in part by stimulating the influx of CD163+ macrophages. Here, we explored the hypothesis that CD163+ macrophages cause plaque progression through the induction of proapoptotic endothelial-to-mesenchymal transition (EndMT) within the fibrous cap. METHODS: Human coronary artery sections from CVPath's autopsy registry were selected for pathological analysis. Athero-prone ApoE-/- and ApoE-/-/CD163-/- mice were used for in vivo studies. Human peripheral blood mononuclear cell-induced macrophages and human aortic endothelial cells were used for in vitro experiments. RESULTS: In 107 lesions with acute coronary plaque rupture, 55% had pathological evidence of intraplaque hemorrhage in nonculprit vessels/lesions. Thinner fibrous cap, greater CD163+ macrophage accumulation, and a larger number of CD31/FSP-1 (fibroblast specific protein-1) double-positive cells and TUNEL (terminal deoxynucleotidyl transferase-dUTP nick end labeling) positive cells in the fibrous cap were observed in nonculprit intraplaque hemorrhage lesions, as well as in culprit rupture sections versus nonculprit fibroatheroma sections. Human aortic endothelial cells cultured with supernatants from hemoglobin/haptoglobin-exposed macrophages showed that increased mesenchymal marker proteins (transgelin and FSP-1) while endothelial markers (VE-cadherin and CD31) were reduced, suggesting EndMT induction. Activation of NF-κB (nuclear factor kappa ß) signaling by proinflammatory cytokines released from CD163+ macrophages directly regulated the expression of Snail, a critical transcription factor during EndMT induction. Western blot analysis for cleaved caspase-3 and microarray analysis of human aortic endothelial cells indicated that apoptosis was stimulated during CD163+ macrophage-induced EndMT. Additionally, CD163 deletion in athero-prone mice suggested that CD163 is required for EndMT and plaque progression. Using single-cell RNA sequencing from human carotid endarterectomy lesions, a population of EndMT was detected, which demonstrated significant upregulation of apoptosis-related genes. CONCLUSIONS: CD163+ macrophages provoke EndMT, which may promote plaque progression through fibrous cap thinning.

Myocardial Bridge and Atherosclerosis, an Intimal Relationship.

PURPOSE OF REVIEW: This review investigates the relationship between myocardial bridges (MBs), intimal thickening in coronary arteries, and Atherosclerotic cardiovascular disease. It focuses on the role of mechanical forces, such as circumferential strain, in arterial wall remodeling and aims to clarify how MBs affect coronary artery pathology. REVIEW FINDINGS: MBs have been identified as influential in modulating coronary artery intimal thickness, demonstrating a protective effect against thickening within the MB segment and an increase in thickness proximal to the MB. This is attributed to changes in mechanical stress and hemodynamics. Research involving arterial hypertension models and vein graft disease has underscored the importance of circumferential strain in vascular remodeling and intimal hyperplasia. Understanding the complex dynamics between MBs, mechanical strain, and vascular remodeling is crucial for advancing our knowledge of coronary artery disease mechanisms. This could lead to improved management strategies for cardiovascular diseases, highlighting the need for further research into MB-related vascular changes.

Level of Perivascular Inflammation Is Significantly Lower Around the Left Internal Mammary Artery Than Around Native Coronary Arteries.

BACKGROUND: The left internal mammary artery (LIMA) is protected from developing atherosclerosis. Perivascular inflammation, which is closely associated with atherosclerosis, can be measured by perivascular adipose tissue attenuation on computed tomography angiography. Whether the absence of atherosclerosis in LIMA is related to the lower level of perivascular inflammation is unknown. This study was performed to compare the level of perivascular inflammation between LIMA in situ and native coronary arteries in patients with coronary artery disease. METHODS AND RESULTS: A total of 573 patients who underwent both computed tomography angiography and optical coherence tomography imaging were included. The level of perivascular adipose tissue attenuation between LIMA in situ and coronary arteries was compared. Perivascular adipose tissue attenuation around LIMA in situ was significantly lower around the 3 coronary arteries (-82.9 [-87.3 to -78.0] versus -70.8 [-75.9 to -65.9]; P<0.001), irrespective of the level of pericoronary inflammation or the number of vulnerable features on optical coherence tomography. When patients were divided into high and low pericoronary inflammation groups, those in the high inflammation group had more target vessel failure (hazard ratio, 2.97 [95% CI, 1.16-7.59]; P=0.017). CONCLUSIONS: The current study demonstrated that perivascular adipose tissue attenuation was significantly lower around LIMA in situ than around native coronary arteries. The lower level of perivascular inflammation may be related to the low prevalence of atherosclerosis in LIMA. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04523194.

Atherosclerotic Coronary Plaque Features in Patients With Chronic Obstructive Pulmonary Disease and Acute Coronary Syndrome.

Previous studies reported a robust relation between chronic obstructive pulmonary disease (COPD) and coronary artery disease (CAD). Systemic inflammation has been proposed as possible pathogenetic mechanism linking these 2 entities, although data on atherosclerotic coronary features in COPD patients are lacking. We studied atherosclerotic coronary plaque features in COPD patients presenting with acute coronary syndrome (ACS) using optical coherence tomography (OCT). ACS patients who underwent intracoronary OCT imaging of the culprit vessel were enrolled. Coronary plaque characteristics and OCT-defined macrophage infiltration (MØI) were assessed by OCT. ACS patients were divided into 2 groups according to the presence of an established diagnosis of COPD, and plaque features at the culprit site and along the culprit vessel were compared between the groups. Of 146 ACS patients (mean age:66.1 ± 12.7 years, 109 men), 47 (32.2%) had COPD. Patients with COPD had significantly higher prevalence of MØI (78.7% vs 54.5%, p = 0.005) and thin cap fibroatheroma (TCFA) (48.9% vs 22.2%, p = 0.001) at the culprit site. In the multivariate logistic regression, COPD was independently associated with MØI (odds ratio [OR] 21.209, 95% confidence interval [CI] 1.679 to 267.910, p = 0.018) and TCFA at the culprit site (OR 5.345, 95% CI 1.386 to 20.616, p = 0.015). Similarly, COPD was independently associated with both MØI (OR 3.570, 95% CI 1.472 to 8.658, p = 0.005) and TCFA (OR 4.088, 95% CI 1.584 to 10.554, p = 0.004) along the culprit vessel. In conclusion, in ACS patients who underwent OCT imaging of the culprit vessel, COPD was an independent predictor of plaque inflammation and vulnerability. These results may suggest that a higher inflammatory milieu in COPD patients might enhance local coronary inflammation, promoting CAD development and plaque vulnerability.

CircTOP1 targeted regulation of PTBP1 expression promotes the progression of coronary artery calcification.

Coronary artery calcification (CAC) is a hallmark event in the pathogenesis of cardiovascular disease, involving the phenotypic transformation of vascular smooth muscle cells (VSMC) towards an osteogenic state. Despite this understanding, the molecular mechanisms governing the VSMC osteogenic switch remain incompletely elucidated. Here, we sought to examine the potential role of circular RNA (circRNA) in the context of CAC. Through transcriptome analysis of circRNA-seq, we identified circTOP1 as a potential candidate circRNA in individuals with CAC. Furthermore, we observed that overexpression of circTOP1 exacerbated vascular calcification in a CAC model. Subsequent pull-down assays revealed an interaction between circTOP1 and PTBP1, a putative target gene of circTOP1 in the context of CAC. In both in vivo and in vitro experiments, we observed heightened expression of circTOP1 and PTBP1 in the CAC model, and noted that reducing circTOP1 expression effectively reduced calcium salt deposits and mineralized nodules in model mice. Additionally, in vitro experiments demonstrated that overexpression of PTBP1 reversed the weakening of signaling caused by silencing circTOP1, thereby exacerbating the osteogenic transition and calcification of VSMC. Collectively, our findings suggested that circTOP1 promotes CAC by modulating PTBP1 expression to mediate VSMC transdifferentiation.

Predictive nomogram model for severe coronary artery calcification in end-stage kidney disease patients.

INTRODUCTION: The Agatston coronary artery calcification score (CACS) is an assessment index for coronary artery calcification (CAC). This study aims to explore the characteristics of CAC in end-stage kidney disease (ESKD) patients and establish a predictive model to assess the risk of severe CAC in patients. METHODS: CACS of ESKD patients was assessed using an electrocardiogram-gated coronary computed tomography (CT) scan with the Agatston scoring method. A predictive nomogram model was established based on stepwise regression. An independent validation cohort comprised of patients with ESKD from multicentres. RESULTS: 369 ESKD patients were enrolled in the training set, and 127 patients were included in the validation set. In the training set, the patients were divided into three subgroups: no calcification (CACS = 0, n = 98), mild calcification (0 < CACS ≤ 400, n = 141) and severe calcification (CACS > 400, n = 130). Among the four coronary branches, the left anterior descending branch (LAD) accounted for the highest proportion of calcification. Stepwise regression analysis showed that age, dialysis vintage, ß-receptor blocker, calcium-phosphorus product (Ca × P), and alkaline phosphatase (ALP) level were independent risk factors for severe CAC. A nomogram that predicts the risk of severe CAC in ESKD patients has been internally and externally validated, demonstrating high sensitivity and specificity. CONCLUSION: CAC is both prevalent and severe in ESKD patients. In the four branches of the coronary arteries, LAD calcification is the most common. Our validated nomogram model, based on clinical risk factors, can help predict the risk of severe coronary calcification in ESKD patients who cannot undergo coronary CT analysis.