Calcified Atherosclerotic Plaque Research Articles

Carotid Artery Calcification Detected on Panoramic Radiography Is Significantly Related to Cerebrovascular Accident, Coronary Artery Disease, and Poor Oral Health: A Retrospective Cross-Sectional Study.

Panoramic radiography imaging modality is widely used by dentists for diagnosing dental and jaw conditions. It can also detect carotid artery calcification (CAC), indicative of calcified atherosclerotic plaques in the carotid arteries. This cross-sectional retrospective study at the University of Tennessee Health Science Center investigated the link between CAC identified on panoramic radiograph (PR) and cerebrovascular accident (CVA), coronary artery disease (CAD), and poor oral health. Data from 314 CAC patients collected from 2014 to 2023 included age at diagnosis, gender, and clinical histories of hypertension, hyperlipidemia, diabetes mellitus, CVA, CAD, and the decay, missing, and filled permanent teeth (DMFT) index. These patients were age- and gender-matched with non-CAC patients for analysis. The findings revealed high prevalences of hypertension (86.2%), hyperlipidemia (57.6%), diabetes mellitus (30.7%), CVA (15.5%), and CAD (28.7%) amongst CAC patients and the average DMFT index was 26.6. A comparative analysis of 276 matched controls demonstrated significant differences in hypertension (85.9% vs. 57.6%), hyperlipidemia (58.3% vs. 33.7%), diabetes (32.6% vs. 22.1%), CVA history (14.9% vs. 5.1%), CAD (26.1% vs. 9.8%), and DMFT scores (26.3 vs. 23.7), all indicating strong associations between CAC and these health conditions. The adjusted analysis showed that hypertension (aOR: 3.20 [95% CI: 2.06-5.07]), hyperlipidemia (aOR: 1.70 [95% CI: 1.14-2.50]), CVA (aOR: 2.20 [95% CI: 1.13-4.30]), and CAD (aOR: 2.10 [95% CI: 1.28-3.60]) were significantly associated with CAC. Notably, only 41.7% of the patients received a medical consultation after CAC detection on PR. It is crucial for dentists to refer patients for further evaluation.

Characterization of Atherosclerotic Mice Reveals a Sex-Dependent Susceptibility to Plaque Calcification but No Major Changes in the Lymphatics in the Arterial Wall.

Lymphatics participate in reverse cholesterol transport, and their presence in the arterial wall of the great vessels and prior experimental results suggest their possible role in the development of atherosclerosis. The aim of this study was to characterize the lymphatic vasculature of the arterial wall in atherosclerosis. Tissue sections and tissue-cleared aortas of wild-type mice unveiled significant differences in the density of the arterial lymphatic network throughout the arterial tree. Male and female Ldlr-/- and ApoE-/- mice on a Western diet showed sex-dependent differences in plaque formation and calcification. Female mice on a Western diet developed more calcification of atherosclerotic plaques than males. The lymphatic vessels within the aortic wall of these mice showed no major changes regarding the number of lymphatic junctions and end points or the lymphatic area. However, female mice on a Western diet showed moderate dilation of lymphatic vessels in the abdominal aorta and exhibited indications of increased peripheral lymphatic function, findings that require further studies to understand the role of lymphatics in the arterial wall during the development of atherosclerosis.

Circulating miR-6821-5p levels and coronary calcification in asymptomatic familial hypercholesterolemia patients

Background and aimsPremature atherosclerotic cardiovascular disease (CVD) is a clinic characteristic of familial hypercholesterolemia (FH). Coronary calcium score (CCS) is a highly used imaging modality to evidence atherosclerotic plaque burden. microRNAs (miRNAs) are non-coding RNAs that epigenetically regulate gene expression. Here, we investigated whether CCS associates with a specific miRNA-signature in FH-patients. MethodsPatients with genetic diagnosis of FH (N = 86) from the nationwide SAFEHEART-cohort were investigated by computed tomography angiography imaging and classified depending on the presence of coronary calcification in FH-CCS (+) and FH-CCS (−) groups by the Agatston score. Differential miRNA profiling was performed in two stages: first by Affymetrix microarray technology (high-throughput differential profiling-studies) and second by RT-PCR using TaqMan-technology (analytical RT-qPCR study) in plasma of the two patient groups. ResultsmiR-193a-5p, miR-30e-5p and miR-6821-5p levels were significantly higher in FH-CCS (+) compared to FH-CCS (−). miR-6821-5p was the best miRNA to discriminate FH-patients CCS(+), according to receiver operating characteristic (ROC) analysis (AUC: 0.70 ± 0.06, p = 0.006). High miR-6821-5p levels were associated with older age (p = 0.03) and high LDL-burden (p = 0.014) using a ROC-derived cut-off value. However, miR-6821-5p did not correlate with age in either the CCS- or CCS + group. Genes involved in calcification processes were identified by in silico analysis. The relation of cell-calcification and expression levels of miR-6821-5p, BMP2 and SPP1 was validated experimentally in human vascular smooth muscle cell cultures. ConclusionsUp-regulated levels of miR-6821-5p are found in the plasma of asymptomatic FH-patients with coronary calcified atherosclerotic plaques, as well as in isolated human vascular smooth muscle cells expressing the pro-calcification genes BMP2 and SPP1. These findings highlight the impact of epigenetic regulation on the development of subclinical atherosclerosis.

Predictors of coronary artery calcium burden in asymptomatic patients with newly diagnosed type 2 diabetes mellitus.

Long-standing diabetes mellitus is often associated with cardiovascular complications. We aimed to evaluate the presence, extent and composition of subclinical atherosclerotic plaques in coronary arteries by Computed Tomography in patients with newly diagnosed type 2 diabetes mellitus (NDT2DM), and to identify the predictors. In this study 101 consecutive patients with NDT2DM were included. Patients were categorized into five groups based on their Coronary Artery Calcium Score (CACS) ranging from 0, 0-10, 11-100, 101-400 to >400. All parameters were compared across these groups. The average patient age was 54.4 ± 11.6years and 48 (47.5%) were females. Eight (7.9%) patients had CACS 0, 6.9% CACS 1-10, 42.6% CACS 11-100, 22.8% CACS 101-400 and 19.8% had CACS >400. Multiple regression analysis for the general data identified weight (p = .04) and systolic blood pressure (p = .033) as independent predictors for CACS. Asymptomatic patients with NDT2DM in more than 90% of cases may present with calcified atherosclerotic plaques and this may be predicted by: patient weight and the level of systolic arterial pressure. Our study emphasizes the need for comprehensive care and early prevention of cardiovascular complications in individuals with NDT2DM.

Hyperparathyroidism and Peripheral Arterial Disease.

Primary hyperparathyroidism (PHPT) is presented in various forms, including classic PHPT, characterised by increased parathyroid hormone (PTH) secretion, normohormonal PHPT, and normocalcaemic PHPT. Secondary hyperparathyroidism is characterised by increased PTH secretion triggered by factors such as vitamin D deficiency and kidney failure. This review aims to discuss the involvement of hyperparathyroidism (HPT) in atherosclerosis, including peripheral arterial disease (PAD). The increased level of PTH is involved in developing subclinical and overt vascular diseases, encompassing endothelial dysfunction, vascular stiffness, hypertension, and coronary and peripheral arterial diseases. It has been consistently associated with an augmented risk of cardiovascular morbidity and mortality, independent of classical risk factors for atherosclerosis. Chronic hypercalcemia associated with increased levels of PTH contributes to the development of calcification of vessel walls and atherosclerotic plaques. Vascular calcification can occur in the intima or media of the arterial wall and is associated with stiffness of peripheral arteries, which the formation of atherosclerotic plaques and narrowing of the vessel lumen can follow. For treating hyperparathyroidism, particularly SHPT, calcimimetics, novel phosphorus binders and novel vitamin D receptor activators are used. However, they are ineffective in severe PHPT. Therefore, parathyroidectomy remains the primary therapeutic option of PHPT.

The Significance of Coronary Artery Calcification for Percutaneous Coronary Interventions.

The prevalence of calcium deposits in coronary arteries grows with age. Risk factors include, e.g., diabetes and chronic kidney disease. There are several underlying pathophysiological mechanisms of calcium deposition. Severe calcification increases the complexity of percutaneous coronary interventions. Invasive techniques to modify the calcified atherosclerotic plaque before stenting have been developed over the last years. They include balloon- and non-balloon-based techniques. Rotational atherectomy has been the most common technique to treat calcified lesions but new techniques are emerging (orbital atherectomy, intravascular lithotripsy, laser atherectomy). The use of intravascular imaging (intravascular ultrasound and optical coherence tomography) is especially important during the procedures in order to choose the optimal strategy and to assess the final effect of the procedure. This review provides an overview of the role of coronary calcification for percutaneous coronary interventions.

Distal embolization of calcified atherosclerotic plaque fragment re-sulting in “balloon uncrossable lesion” during elective percutaneo-us coronary intervention

Distal embolization of calcified atherosclerotic plaque fragment re-sulting in “balloon uncrossable lesion” during elective percutaneo-us coronary intervention

Abstract TP143: Longitudinal Evaluation of Vessel Wall MRI Demonstrates Bilaterally Symmetric Evolution of Carotid Atherosclerosis

Introduction: Carotid atherosclerosis is a leading cause of stroke worldwide. Previous studies demonstrated bilateral symmetry in atherosclerotic plaque burden and calcification scores. By leveraging longitudinal 3D vessel wall MRI, this study aims to investigate if there is a symmetrical trend of bilateral plaque progression. Methods: Asymptomatic patients with confirmed carotid stenosis were prospectively recruited in the study. Subjects underwent baseline and follow-up 3D vessel wall imaging for a time span up to 8 years. A deep learning-based pipeline was used to bilaterally segment the carotid lumen and vessel wall on axial image slices. Within each artery, the range of slices with wall thickness > 2mm on any scan was included as potential atherosclerotic plaque. Plaque burden, positively associated with stroke risk, was defined as the percent wall volume (wall volume / total vessel volume х 100%). For each plaque, a linear model was fitted across all available time points to determine the growth rate of plaque burden. We used generalized estimating equation-based linear regression models to evaluate associations of the growth rate of each side with the contralateral side, adjusted for clinical risk factors and medications. Effect sizes were summarized using the partial correlation coefficient. Results: 20 subjects (mean age 73.5 years, 3 females, 14 on statins) who underwent at least three scans with bilateral carotid plaque were included in the analysis. Each subject underwent an average of 4.8 scans over 5.2 years. Overall, the plaque growth rate of one side was moderately correlated with the contralateral side (r=0.50, p=0.004), even after adjusting for age, sex and statins use. Then, for each subject, the larger of the two plaques at baseline (left or right side) was identified. The growth rate of the larger plaque was also predictive of the growth rate of the smaller plaque over the same time period (r=0.66, p=0.004). Conclusion: The systemic nature of atherosclerotic disease entails an association in symmetrical disease evolution for left and right carotid arteries. In bilaterally diseased patients, the longitudinal monitoring of the more advanced carotid lesion may provide prognostic information on the less advanced contralateral plaque.

Genetic Predisposition of Atherosclerotic Cardiovascular Disease in Ancient Human Remains.

Several computed tomographic studies have shown the presence of atherosclerosis in ancient human remains. However, while it is important to understand the development of atherosclerotic cardiovascular disease (ASCVD), genetic data concerning the prevalence of the disease-associated single nucleotide polymorphisms (SNPs) in our ancestors are scarce. For a better understanding of the role of genetics in the evolution of ASCVD, we applied an enrichment capture sequencing approach to mummified human remains from different geographic regions and time periods. Twenty-two mummified individuals were analyzed for their genetic predisposition of ASCVD. Next-generation sequencing methods were applied to ancient DNA (aDNA) samples, including a novel enrichment approach specifically designed to capture SNPs associated with ASCVD in genome-wide association studies of modern humans. Five out of 22 ancient individuals passed all filter steps for calculating a weighted polygenic risk score (PRS) based on 87 SNPs in 56 genes. PRSs were correlated to scores obtained from contemporary people from around the world and cover their complete range. The genetic results of the ancient individuals reflect their phenotypic results, given that the only two mummies showing calcified atherosclerotic arterial plaques on computed tomography scans are the ones exhibiting the highest calculated PRSs. These data show that alleles associated with ASCVD have been widespread for at least 5,000 years. Despite some limitations due to the nature of aDNA, our approach has the potential to lead to a better understanding of the interaction between environmental and genetic influences on the development of ASCVD.

The Identification Potential of Atherosclerotic Calcifications in the Context of Forensic Anthropology.

Atherosclerosis is an inflammatory disease that, in its more developed stages, can lead to the calcification of fatty plaques on the walls of arteries, resulting in the appearance of new bone elements. It is a condition that has been studied and documented little in the context of paleopathology, especially in the framework of forensic anthropology. This article analyzed the skeletal remains of 71 individuals (35 females and 36 males) from the Luís Lopes Identified Collection of the National Museum of Natural History and Science in Lisbon, 31 of whom had an autopsy report. An attempt was made to ascertain whether these bone elements resulting from atherosclerotic calcification would resist cadaveric decomposition and whether they would be recoverable several years after burial, and a survey was carried out of their distribution according to sex and age, as well as their association with other pathologies, such as osteoporosis and cardiac and renal pathologies. An imaging analysis of an atherosclerotic plaque was also carried out to complement the macroscopic analysis and present other methods of identifying plaques. It was concluded that each atherosclerotic calcification has a unique profile, which can be useful for identification, especially in cases where the individual shows a severe condition. In terms of identification potential, the analysis of calcified atherosclerotic plaques can be useful, as they can corroborate or reject an identification. However, it always requires the existence of ante-mortem imaging exams and must always be used in addition to other identification methods. Regardless of the identification, these plaques are bone elements resulting from a pathology and should, therefore, be known and recognized by the scientific community.

Investigation of Calcified Atherosclerotic Plaques on Panoramic Radiographs

Aim: This study aims to determine the prevalence of calcified atherosclerotic plaques (CAPs) incidentally encountered in the carotid artery within panoramic radiography (PR) images. Materials and Methods: A total of 1200 patients (646 females, 554 males) referred to our clinic in January 2022 and January 2023 were included. CAPs within PRs were assessed, with data stratified by gender, age, and systemic conditions. Statistical analysis employed descriptive statistics and chi-square tests (p<0.05). Results: Among the 1200 patients, 251 CAPs (20.92%) were detected, with 128 (50.1%) occurring in females and 123 (49.9%) in males. The gender-based analysis demonstrated no statistically significant disparity in CAPs occurrence. Conversely, a notable correlation was established between the incidence of CAPs and age groups as well as systemic conditions (p<0.05). Conclusion: Panoramic radiography, routinely used in dental practice, offers a cost-effective, low-radiation means for preliminary CAPs assessment. Dental practitioners should consider referring patients with identified CAPs in PRs to cardiology departments, potentially reducing stroke risks.

The Role of Osteopontin in Atherosclerosis and Its Clinical Manifestations (Atherosclerotic Cardiovascular Diseases)-A Narrative Review.

Atherosclerotic cardiovascular diseases (ASCVDs) are the most common and severe public health problem nowadays. Osteopontin (OPN) is a multifunctional glycoprotein highly expressed at atherosclerotic plaque, which has emerged as a potential biomarker of ASCVDs. OPN may act as an inflammatory mediator and/or a vascular calcification (VC) mediator, contributing to atherosclerosis progression and eventual plaque destabilization. In this article, we discuss the complex role of OPN in ASCVD pathophysiology, since many in vitro and in vivo experimental data indicate that OPN contributes to macrophage activation and differentiation, monocyte infiltration, vascular smooth muscle cell (VSMC) migration and proliferation and lipid core formation within atherosclerotic plaques. Most but not all studies reported that OPN may inhibit atherosclerotic plaque calcification, making it "vulnerable". Regarding clinical evidence, serum OPN levels may become a biomarker of coronary artery disease (CAD) presence and severity. Significantly higher OPN levels have been found in patients with acute coronary syndromes than those with stable CAD. In limited studies of patients with peripheral artery disease, circulating OPN concentrations may be predictive of future major adverse cardiovascular events. Overall, the current literature search suggests the contribution of OPN to atherosclerosis development and progression, but more robust evidence is required.

In vivo evaluation of intravascular lithotripsy in a healthy porcine coronary model

Abstract Objectives In this study, we aimed to investigate the vascular response to an intravascular lithotripsy (IVL) shockwave balloon in a healthy porcine coronary artery model. Background IVL is a novel clinical technique for modifying heavily calcified atherosclerotic plaques. Methods A total of 24 porcine coronary arteries were treated with IVL or plain old balloon angioplasty (POBA). Histology, histomorphometry, quantitative coronary angiography analysis (QCA), and optical coherence tomography (OCT) were performed post-procedure and at 1-month follow-up (1M-FU). Results There was no significant difference in the late lumen loss and diameter stenosis (determined by QCA) and the minimal lumen area (evaluated by OCT) of the IVL and POBA groups at 1M-FU. Pathological analysis revealed that the lumen and neointima areas were similar between the two groups. However, the medial and adventitial layers were more prominent in the IVL than in the POBA group. The injury score and inflammation of the media and adventitia increased dramatically in the IVL group post-procedure and at 1M-FU. At 1M-FU, media fibrin deposition and adventitial fibrosis were also significantly increased in the IVL group. However, there was no significant difference in neointima fibrin deposition, endothelialization, and thrombosis between both groups. Layered separation of the media and adventitia was observed in the IVL group. Conclusion The findings indicate that the IVL balloon did not cause serious intimal hyperplasia and endothelial damage compared with the effects of POBA in the healthy coronary artery. However, shock waves may cause unique damage to the vascular media and adventitia in the coronary artery, which was not observed in the peripheral artery.Device introductionPathological image at 1M FU

Experimental Investigation of the Calcified Plaque Material Removal Rate in Coronary Rotational Atherectomy

Abstract Rotational atherectomy (RA) is a minimally invasive procedure to remove the calcified atherosclerotic plaque from arteries to restore blood flow. It uses a high-speed, metal-bonded diamond abrasive grinding wheel to pulverize the calcified plaque into absorbable debris via a catheter through the artery. Although RA has been clinically used for over two decades, procedural complications persist and there remains a lack of consensus on the optimal device parameters. This study aims to investigate the material removal rate (MRR) in coronary RA with respect to grinding wheel sizes and rotational speeds based on a tissue-mimicking phantom. Three grinding wheel sizes, 1.25, 1.5, and 1.75 mm in diameter, and three rotational speeds, 1,20,000, 1,50,000, and 1,80,000 rpm, were investigated. The RA MRR was presented as the luminal area gain and measured by microscopy and image processing. The results show the increase in the grinding wheel size or rotational speed leads to a higher MRR and luminal gain in RA. With a 1.75 mm diameter grinding wheel rotating at 1,80,000 rpm in a 2 mm initial diameter lumen, the max MRR and the luminal gain are 2.49 mm2/three passes and 5.09 mm2, respectively. The MRR decreases as the number of grinding passes increases during RA with the same grinding wheel rotating at a constant speed. This study provides a thorough understanding of the wheel size and speed effects on coronary RA MRR for potential improvements in RA devices and clinical operational guidelines.

Wnt signaling pathway and sclerostin in the development of atherosclerosis and vascular calcification.

Atherosclerosis is a complex process involving endothelial dysfunction, vascular inflammation, vascular smooth muscle cell (VSMC) proliferation, angiogenesis, and calcification. One of the pathomechanisms of atherosclerosis is the upregulation of Wnt signaling. This study aimed to summarize the current knowledge regarding the role of Wnt signaling and sclerostin in atherosclerosis, vascular calcification, aneurysms, and mortality based on the PubMed database. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendation and identified 160 papers that were included in this systematic review. The published data highlight that the upregulation of Wnt components facilitates the initiation and progression of atherosclerosis, arterial remodeling, VSMCs proliferation and phenotypic transition to the osteoblastic lineage in the arterial wall. This results in protein secretion, cell migration, calcification, fibrosis and aneurysm formation. The transformation of VSMCs into osteoblast-like cells that is observed in atherosclerosis results in sclerostin expression inhibiting the Wnt pathway. Furthermore, it was shown that sclerostin, expressed in atherosclerotic plaques, inhibits aneurysm formation in a mouse model. However, in humans, while the antisclerostin antibody romosozumab inhibits bone resorption, biochemical parameters of endothelial activation and inflammation are not affected, and the incidence of aneurysms is not increased. It was suggested that detecting sclerostin in the calcified aortic atherosclerotic plaques reflects a defense mechanism against Wnt activation and inhibition of atherosclerosis, although this has only been shown in animal models. Moreover, an increased number of vascular cells converted to osteogenic phenotypes results in increased plasma sclerostin concentrations. Therefore, plasma sclerostin derived from bone limits its importance as a global marker of vascular calcification.

Dişsiz Hastaların Panoramik Radyograflarında Yumuşak Doku Kalsifikasyonlarının Değerlendirilmesi

Aim: It is aimed to evaluate the prevalence, and types of soft tissue calcifications (STCs) on panoramic radiographs of edentulous patients.
 
 Material and Methods: 1308 images were randomly selected from patients who applied to Necmettin Erbakan University for various dental problems in 2020 and 2021. In these radiographs, tonsillolith, sialolith, calcified atherosclerotic plaque (CAP), and stylohyoid ligament calcification (SLC), calcified lymph node, phleboliths, antroliths, rhinoliths, and triticeous and thyroid cartilage calcifications were evaluated. Data were categorized according to gender, systemic disease and calcification type. Descriptive statistics were determined for all parameters. The status of the data according to gender, age group and systemic disease were analyzed by chi-square test (p

Association of potato consumption with calcified atherosclerotic plaques in the coronary arteries: The NHLBI Family Heart Study

Background and aimsWhile the association of potato consumption with risk factors for coronary artery disease has been inconsistent, no data are available in the literature on the influence of potato consumption on subclinical disease. Thus, we sought to examine whether baked/mashed potato consumption is associated with calcified atherosclerotic plaques in the coronary arteries. Methods and ResultsIn a cross-sectional design, we studied 2208 participants of the NHLBI Family Heart Study. These subjects were selected based on their elevated cardiovascular disease risk compared to the general population. Potato consumption was assessed by a semi-quantitative food frequency questionnaire. We defined prevalent CAC using an Agatston score of at least 100 and fitted generalized estimating equations to calculate prevalence odds ratios of CAC. Mean age at initial clinic visit was 58.2 years and 55% were female. Median consumption of potatoes was 2–4/week. There was no statistically significant association between frequency of potato consumption and prevalent CAC: odds ratios (95% CI) for CAC were 1.0 (reference), 0.85 (0.56–1.30), 0.85 (0.58–1.26), and 0.95 (0.60–1.53) among subjects reporting potato consumption of <1/week, 1/week, 2–4/week, and 5+/week, respectively (p for linear trend 0.83), adjusting for age, sex, BMI, smoking, exercise, diabetes, hypertension, total calories, prevalent coronary heart disease, income, education, and daily red meat intake. ConclusionsWe found no significant association between baked/mashed potato consumption and CAC in older adults. Study registration numberNCT00005136. Study registration date: 5/25/2000.

Early Development of Atherosclerotic Plaques in the Coronary Arteries after Radiotherapy for Breast Cancer (BACCARAT Study).

Background-Radiotherapy (RT) for breast cancer (BC) can lead to an increased risk of coronary artery disease several years after RT. The aim of this study was to evaluate the development of overall, non-calcified and calcified atherosclerotic plaques over 2 years after BC for RT and associations with cardiac exposure. Methods-The study included 101 left- or right-sided BC patients treated with RT without chemotherapy. A coronary CT angiography was performed before and 2 years after RT. Plaque development thorough the entire coronary network was defined as an increased number of plaques. Cardiac exposure was quantified with mean doses to the heart, left ventricle, and coronary arteries. Logistic regression models were used to assess association with doses. Results-At inclusion, 37% of patients had plaques, increasing to 42% two years after RT. Overall plaque development was observed in seven patients: five with calcified plaque development and four with non-calcified plaque development. The risk of overall plaque development was significantly associated with doses to the Left Main and Circumflex coronary arteries (OR at 1 Gy = 2.32, p = 0.03 and OR at 1 Gy = 2.27, p = 0.03, respectively). Specific analyses for calcified and non-calcified plaque development showed similar results. Conclusion-Our study suggests an association between coronary arteries exposure and the risk of developing both calcified and non-calcified atherosclerotic plaques over 2 years after BC RT. Trial registration number: NCT02605512.

Association between the prevalence of pulp stones and calcified atherosclerotic plaques: a systematic review and meta-analysis.

To evaluate the association between the prevalence of pulp stones (PS) in permanent teeth and calcified atherosclerotic plaques (CAP). An electronic search was performed in 10 databases to locate observational studies that investigated the association between PS in permanent teeth and CAP, published until March 2022. Two reviewers performed the search, selection and extraction of data from eligible studies. The individual risk of bias of eligible studies was assessed using the JBI Critical Appraisal Tools. The meta-analysis was conducted using fixed and random effects and odds ratio (OR) as an effect measure with a 95% confidence interval (CI). The heterogeneity between the studies was quantified using the I² test. The certainty of evidence was evaluated using the GRADE approach. The electronic search resulted in 2968 records, of which only 7 studies were considered eligible. The total sample consisted of 3770 participants from 5 countries. All studies showed biases of confounding factors and exposure assessment. Based on six studies and with very low certainty of evidence, the meta-analysis showed that patients with PS were more likely to also have CAP in carotid or coronary arteries (OR: 1.70; 95% CI: 1.21; 2.38, I² = 0%). Limited evidence suggests that there is a positive association between the prevalence of PS in permanent teeth detected using panoramic radiography and CAP in the coronary or carotid arteries.

Mast cells participate in smooth muscle cell reprogramming and atherosclerotic plaque calcification

BackgroundCalcification, a key feature of advanced human atherosclerosis, is positively associated with vascular disease burden and adverse events. We showed that macrocalcification can be a stabilizing factor for carotid plaque molecular biology, due to inverse association with immune processes. Mast cells (MCs) are important contributors to plaque instability, but their relationship with macrocalcification is unexplored. With a hypothesis that MC activation negatively associates with carotid plaque macrocalcification, we aimed to investigate the link between MCs and carotid plaque vulnerability, and study MC role in plaque calcification via smooth muscle cells (SMCs). MethodsPre-operative computed tomography angiographies of patients (n = 40) undergoing surgery for carotid stenosis were used to characterize plaque morphology. Plaque microarrays (n = 40 and n = 126) were used for bioinformatic deconvolution of immune cell populations. Tissue microarrays (n = 103) were used to histologically validate the contribution of activated and resting MCs in plaques. ResultsActivated MCs and their typical markers were negatively correlated with macrocalcification. The ratio of activated vs. resting MCs was increased in low-calcified plaques from symptomatic patients. There was no modulating effect of medication on MC ratios. In vitro experiments showed that SMC calcification attenuated MC activation, while both active and resting MCs stimulated SMC calcification and induced dedifferentiation towards a pro-inflammatory-, osteochondrocyte-like phenotype, without modulating their migro-proliferative function. ConclusionsIntegrative analyses from human plaques showed that MC activation is inversely associated with macrocalcification and positively with parameters of plaque vulnerability. Mechanistically, MCs induce SMC osteogenic reprograming, while matrix calcification in turn attenuates MC activation, offering new therapeutic avenues for exploration.