Coronary Plaque Sampling Reveals Molecular Insights Into Coronary Artery Disease.
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ABSTRACT:
SUBMITTER: Widlansky ME
PROVIDER: S-EPMC10467803 | biostudies-literature | 2023 Sep
REPOSITORIES: biostudies-literature
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Coronary Plaque Sampling Reveals Molecular Insights Into Coronary Artery Disease.
Widlansky Michael E ME Liu Yong Y Tumusiime Shakirah S Hofeld Benjamin B Khan Nabeel N Aljadah Michael M Wang Jingli J Anger Amberly A Qiu Qiongzi Q Therani Bhavika B Liu Pengyuan P Liang Mingyu M
Circulation research 20230804 6
Similar Datasets
Project description:We developed a coronary plaque sampling approach that could be applied broadly in live patients with coronary artery disease (CAD) to obtain molecular and cellular insights into human coronary atherosclerosis. Our approach combined RNA retrieval directly from balloons used in percutaneous coronary interventions (PCI) and inexpensive, low-input RNA-Seq using SMART-seq. We generated SMART-Seq libraries from coronary samples from 27 patients. Of the 27 patients, 13 were confirmed to have stable CAD (sCAD) and 14 confirmed to have been performed on lesions causing acute coronary syndrome (ACS). We applied CIBERSORTx to analyze the SMART-seq data from each of the 27 samples. We found fibroblasts and fibromyoctes were enriched, while smooth muscle cells were reduced, in samples from ACS compared with sCAD patients. We identified 371 genes as significantly differential expressed (q<0.05) between sCAD and ACS patients.
2023-07-10 | GSE236610 | GEO
Project description:Coronary Plaque Sampling Reveals Molecular Insights into Coronary Artery Disease
| PRJNA991655 | ENA
Project description:BackgroundThe ability to characterize and to quantify the extent of coronary artery disease has the potential to improve the prognostic capability of coronary computed tomography angiography. Although reproducible techniques have been described in those with mild coronary disease, this has yet to be assessed in patients with advanced disease.MethodsTwenty patients with known multivessel disease underwent repeated computed tomography coronary angiography, 2 weeks apart. Coronary artery segments were analysed using semi-automated software by two trained observers to determine intraobserver, interobserver and interscan reproducibility.ResultsOverall, 149 coronary arterial segments were analysed. There was excellent intraobserver and interobserver agreement for all plaque volume measurements (Lin's coefficient 0.95 to 1.0). There were no substantial interscan differences (P > 0.05 for all) for total (2063 ± 1246 mm3, mean of differences -35.6 mm3), non-calcified (1795 ± 910 mm3, mean of differences -4.3 mm3), calcified (298 ± 425 mm3, mean of differences -31.3 mm3) and low-attenuation (13 ± 13 mm3, mean of differences -2.6 mm3) plaque volumes. Interscan agreement was highest for total and noncalcified plaque volumes. Calcified and low-attenuation plaque (-236.6 to 174 mm3 and -15.8 to 10.5 mm3 respectively) had relatively wider 95% limits of agreement reflecting the lower absolute plaque volumes.ConclusionIn the presence of advanced coronary disease, semi-automated plaque quantification provides excellent reproducibility, particularly for total and non-calcified plaque volumes. This approach has major potential to assess change in disease over time and optimize risk stratification in patients with established coronary artery disease.
| S-EPMC8236495 | biostudies-literature
Project description:Background and aimsHypertension is associated with increased clinical and subclinical coronary artery disease (CAD); however, the relationship between blood pressure and coronary plaque volume is unclear. We examined the effect of systolic blood pressure (SBP) and diastolic blood pressure (DBP) on coronary artery plaque volume.Methods285 subjects with stable CAD on statin therapy underwent coronary computed tomographic angiography to measure volume of fatty, fibrous, noncalcified, calcified and total coronary plaque.ResultsMean (SD) age was 63.1 (7.7); mean (SD) LDL-C, 78.7 mg/dL (28.5). Compared to the highest DBP tertile (>76 mmHg), those in the lowest DBP tertile (≤68 mmHg) had lower volumes of fatty: 10.0 vs. 7.7 mm3/mm, (p trend = 0.042), fibrous: 19.6 vs. 13.8 mm3/mm (p trend = 0.011), non-calcified: 29.7 vs. 22.5 mm3/mm (p trend = 0.017) and total plaque: 37.8 vs. 25.1 mm3/mm (p trend = 0.010) whereas there was no relationship with SBP tertiles. Similarly, when examined as a continuous variable, higher DBP was a significant independent predictor of higher plaque volume after multivariate adjustment: for every 1 mmHg increase in DBP, fibrous plaque increased 0.128 mm3/mm (p = 0.022), noncalcified plaque increased 0.176 mm3/mm (p = 0.045), calcified plaque increased 0.096 mm3/mm (p = 0.001) and total plaque increased 0.249 mm3/mm (p = 0.019) whereas SBP ranging from 95 to 154 mmHg did not predict plaque volume.ConclusionsLevel of DBP predicts coronary plaque with a DBP tertile ≤68 mmHg associated with the least amount of coronary plaque in subjects with LDL-C < 80 mg/dL.
| S-EPMC7963403 | biostudies-literature
Project description:ObjectivesPatients with familial hypercholesterolemia (FH) are at a very high risk of coronary artery diseases. The aim of the present study was to clarify the characteristics of coronary plaque in patients with FH.Designand Methods: A total of 569 patients who underwent optical coherence tomography (OCT) imaging of culprit plaque were included. The characteristics of culprit plaque were compared between patients with and without FH.ResultsA total of 38 patients (6.7%) were clinically diagnosed with FH. The location of the culprit plaque was significantly different (p < 0.001) with a trend toward higher frequency of left main lesion in the FH group than in the group with no FH (7.9 vs. 0%). Culprit plaque was significantly shorter in patients with FH than those without FH (28.1 vs. 33.2 mm, p = 0.016). A trend toward higher prevalence of plaque with macrophage accumulation in patients with FH than those without FH (50.0 vs. 34.7%, p = 0.056) was observed, although the prevalence of other vulnerable characteristics including thin-cap fibroatheroma (TCFA) was comparable between patients with and without FH. Among patients with FH, significant increases in the prevalence of lipid-rich plaque (p = 0.028) and TCFA (p = 0.003) were observed according to the increase in low-density lipoprotein cholesterol (LDL-C) levels.ConclusionsPatients with FH had shorter culprit plaque without significant difference in the prevalence of vulnerable plaque components compared with patients without FH. A higher LDL-C level was associated with higher prevalence of vulnerable plaque in patients with FH.
| S-EPMC7895842 | biostudies-literature
Project description:Background Polygenic risk scores (PRSs) based on risk variants from genome-wide association studies predict coronary artery disease (CAD) risk. However, it is unknown whether the PRS is associated with specific CAD characteristics. Methods and Results We consecutively included 1645 patients with suspected stable CAD undergoing coronary computed tomography angiography. A multilocus PRS was calculated as the weighted sum of CAD risk variants. Plaques were evaluated using an 18-segment model and characterized by stenosis severity and composition (soft [0%-19% calcified], mixed-soft [20%-49% calcified], mixed-calcified [50%-79% calcified], or calcified [≥80% calcified]). Coronary artery calcium score and segment stenosis score were used to characterize plaque burden. For each standard deviation increase in the PRS, coronary artery calcium score increased by 78% (P=4.1e-26) and segment stenosis score increased by 16% (P=2.4e-29) in the fully adjusted model. The PRS was associated with a higher prevalence of obstructive plaques (odds ratio [OR]: 1.78, P=5.6e-16), calcified (OR: 1.69, P=6.5e-17), mixed-calcified (OR: 1.67, P=7.3e-9), mixed-soft (OR: 1.45, P=1.6e-6), and soft plaques (OR: 1.49, P=2.5e-6), and a higher prevalence of plaque in each coronary vessel (all P<1.0e-4). However, when analyzing data on a plaque level (3007 segments with plaque in 849 patients) the PRS was not associated with stenosis severity, plaque composition, or localization (all P>0.05). Conclusions Our results suggest that polygenic risk based on large genome-wide association studies increases CAD risk through an increased burden of coronary atherosclerosis rather than promoting specific plaque features. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02264717.
| S-EPMC7033858 | biostudies-literature
Project description:BackgroundImpaired glucose tolerance (IGT) patients are known to have a high risk of cardiovascular events and their prognosis has been reported to be poor. The present study aimed to compare coronary plaque characteristics among coronary artery disease (CAD) patients with normal glucose tolerance (NGT), those with IGT, and those with diabetes mellitus (DM) by using optical coherence tomography (OCT).MethodsThe present study included 101 coronary artery disease patients (mean age, 67.9 ± 10.4 years; 82.4% male). OCT was performed for target and non-target vessels during percutaneous coronary intervention. The patients were divided into the following 3 groups: the NGT, IGT, and DM groups.ResultsA total of 136 non-target residual plaques were found in 101 patients (27, 30, and 44 in the NGT, IGT, and DM groups, respectively). The size of the lipid core expressed as the mean angle of the lipid arc was significantly greater in the IGT and DM groups than in the NGT group (163.0 ± 58.7°, 170.1 ± 59.3°, and 130.9 ± 37.7°, respectively, P < 0.05). The fibrous cap covering the lipid core was significantly thinner in the IGT group than in the NGT group (77.0 ± 23.4 μm vs. 105.6 ± 47.0 μm, P = 0.040).ConclusionThe coronary plaques in CAD patients are more vulnerable when having IGT compared to those with NGT, and similar to those with DM. This finding may explain the high risk of cardiovascular events in CAD patients with IGT.
| S-EPMC5147949 | biostudies-literature
Project description:The majority of the heritability of coronary artery disease (CAD) remains unexplained, despite recent successes of genome-wide association studies (GWAS) in identifying novel susceptibility loci. Integrating functional genomic data from a variety of sources with a large-scale meta-analysis of CAD GWAS may facilitate the identification of novel biological processes and genes involved in CAD, as well as clarify the causal relationships of established processes. Towards this end, we integrated 14 GWAS from the CARDIoGRAM Consortium and two additional GWAS from the Ottawa Heart Institute (25,491 cases and 66,819 controls) with 1) genetics of gene expression studies of CAD-relevant tissues in humans, 2) metabolic and signaling pathways from public databases, and 3) data-driven, tissue-specific gene networks from a multitude of human and mouse experiments. We not only detected CAD-associated gene networks of lipid metabolism, coagulation, immunity, and additional networks with no clear functional annotation, but also revealed key driver genes for each CAD network based on the topology of the gene regulatory networks. In particular, we found a gene network involved in antigen processing to be strongly associated with CAD. The key driver genes of this network included glyoxalase I (GLO1) and peptidylprolyl isomerase I (PPIL1), which we verified as regulatory by siRNA experiments in human aortic endothelial cells. Our results suggest genetic influences on a diverse set of both known and novel biological processes that contribute to CAD risk. The key driver genes for these networks highlight potential novel targets for further mechanistic studies and therapeutic interventions.
| S-EPMC4102418 | biostudies-literature
Project description:This review summarizes recent advances in understanding the development of coronary arteritis in Kawasaki disease. Kawasaki disease is the most common cause of acquired heart disease among children characterized with coronary artery abnormalities, which can cause myocardial ischemia, infarction, and even death. The pathogenic factors of Kawasaki disease and the pathological process of coronary artery disease are not clear at present, which brings challenges to the prevention and treatment of the disease. The treatment of Kawasaki disease focuses mainly on timely administration of intravenous high doses of immunoglobulin and aspirin. However, there are still some patients who do not respond well to this standard treatment, and its management remains a challenge. As a result, coronary artery lesions still occur in patients and affect their quality of life. In this review, we discuss updated research data of Kawasaki disease coronary artery lesions.
| S-EPMC7477115 | biostudies-literature
Project description:BackgroundRisk stratification is crucial to improve tailored therapy in patients with suspected coronary artery disease (CAD). This study investigated the ability of targeted proteomics to predict presence of high-risk plaque or absence of coronary atherosclerosis in patients with suspected CAD, defined by coronary computed tomography angiography (CCTA).MethodsPatients with suspected CAD (n = 203) underwent CCTA. Plasma levels of 358 proteins were used to generate machine learning models for the presence of CCTA-defined high-risk plaques or complete absence of coronary atherosclerosis. Performance was tested against a clinical model containing generally available clinical characteristics and conventional biomarkers.FindingsA total of 196 patients with analyzable protein levels (n = 332) was included for analysis. A subset of 35 proteins was identified predicting the presence of high-risk plaques. The developed machine learning model had fair diagnostic performance with an area under the curve (AUC) of 0·79 ± 0·01, outperforming prediction with generally available clinical characteristics (AUC = 0·65 ± 0·04, p < 0·05). Conversely, a different subset of 34 proteins was predictive for the absence of CAD (AUC = 0·85 ± 0·05), again outperforming prediction with generally available characteristics (AUC = 0·70 ± 0·04, p < 0·05).InterpretationUsing machine learning models, trained on targeted proteomics, we defined two complementary protein signatures: one for identification of patients with high-risk plaques and one for identification of patients with absence of CAD. Both biomarker subsets were superior to generally available clinical characteristics and conventional biomarkers in predicting presence of high-risk plaque or absence of coronary atherosclerosis. These promising findings warrant external validation of the value of targeted proteomics to identify cardiovascular risk in outcome studies. FUND: This study was supported by an unrestricted research grant from HeartFlow Inc. and partly supported by a European Research Area Network on Cardiovascular Diseases (ERA-CVD) grant (ERA CVD JTC2017, OPERATION). Funders had no influence on trial design, data evaluation, and interpretation.
| S-EPMC6355456 | biostudies-literature