scholarly journals Site-Specific Secretome Map Evidences VSMC-Related Markers of Coronary Atherosclerosis Grade and Extent in the Hypercholesterolemic Swine

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Silvia Rocchiccioli ◽  
Antonella Cecchettini ◽  
Nadia Ucciferri ◽  
Marianna Terreni ◽  
Federica Viglione ◽  
...  

A major drawback in coronary atherosclerosis (ATS) research is the difficulty of investigating early phase of plaque growth and related features in the clinical context. In this study, secreted proteins from atherosclerotic coronary arteries in a hypercholesterolemic swine model were characterized by a proteomics approach and their expression was correlated to site-specific ATS stage and extent. A wide coronary artery map of secreted proteins has been obtained in high fat (HF) diet induced ATS swine model and a significantly different expression of many proteins related to vascular smooth muscle cell (VSMC) activation/migration has been identified. Significant associations with ATS stage of HF coronary lesions were found for several VSMC-derived proteins and validated for chitinase 3 like protein 1 (CHI3L1) by tissue immunoexpression. A direct correlationR2=0.85was evidenced with intima to media thickness ratio values and ELISA confirmed the higher blood concentrations of CHI3L1 in HF cases. These findings confirmed the pivotal role of VSMCs in coronary plaque development and demonstrated a strong site-specific relation between VSMC-secreted CHI3L1 and lesion grade, suggesting that this protein could be proposed as a useful biomarker for diagnosing and staging of atherosclerotic lesions in coronary artery disease.

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
D Opincariu ◽  
N Rat ◽  
A Mester ◽  
R Hodas ◽  
D Cernica ◽  
...  

Abstract Funding Acknowledgements Research grant PlaqueImage, contract number 26/01.09.2016, SMIS code 103544, Project funded by the European Union and the Government of Romania Background The coronary CT angiography (CCTA)-based differences in composition, morphology and vulnerability of coronary plaques (CPs), according to their location within the coronary tree, have not been investigated so far. Purpose We sought to perform a comparative analysis between plaques located at different levels within the coronary tree, to identify the differences in plaque composition, morphology, and vulnerability between the three major coronary branches. Methods We conducted a cross-sectional, observational study on 75 patients with stable coronary artery disease who underwent CCTA for assessment of coronary lesions that exhibited at least one vulnerable plaque (VP) in the coronary tree. After image acquisition, coronary plaque analysis was performed with the use of the Syngo.via Frontier (Siemens) software. Plaque analysis also included evaluation of presence of VM: low attenuation plaque – LAP; napkin ring sign – NRS; spotty calcifications – SC; positive remodeling – PR. VP were defined as lesions that presented at least 1 vulnerability marker (VM). In total, 90 coronary VPs located at the level of the left anterior descending (LAD; n = 30), circumflex (CXA; n = 30) and right coronary artery respectively (RCA; n = 30) were identified and analyzed. Results Lesions located in the RCA presented a significantly higher length (LAD - 18.67± 5.49 vs. CXA - 15.48 ±3.73 vs. RCA - 20.47 ± 5.97 mm, p = 0.001), a higher degree of stenosis (LAD - 57.77 ± 8.62 vs. CXA - 54.50 ± 11.25 vs. RCA - 59.63 ± 10.42 mm, p = 0.022), and were more voluminous (LAD - 187.9 ± 86.03 vs. CXA - 146.9 ± 102.4 vs. RCA - 248.1 ± 11.4 mm3, p = 0.0007) compared to those located in the LAD and CXA, but no difference was observed regarding the remodeling (p = 0.180) or eccentricity indexes (p = 0.423). Plaque composition was also significantly different according to plaque location: calcified volume (LAD - 44.07 ± 63.90 vs. CXA - 12.40 ± 19.65 vs. RCA - 33.69 ± 34.38 mm3, p = 0.002), non-calcified volume (LAD - 143.8 ± 76.02 vs. CXA - 134.5 ± 102.2 vs. RCA - 214.4 ± 99.67 mm3, p = 0.002), lipid rich volume (LAD - 14.95 ± 22.69 vs. CXA - 6.44 ± 13.42 vs. RCA -16.07 ± 15.74 mm3, p = 0.0005), fibrotic volume (LAD - 128.9 ± 66.10 vs. CXA - 128.1 ± 91.56 vs. RCA - 198.3 ± 92.34 mm3, p = 0.003). The highest number of VM per plaque was present in the LAD (LAD - 2.2 ± 0.8 vs. CXA - 1.6 ± 0.7 vs. RCA - 1.8 ± 0.6, p = 0.01), as well as highest rate of VPs (LAD – 80%, CXA – 46.6%, RCA – 70%, p = 0.01). No difference was registered between coronary arteries on the presence of SCs (p = 0.670), NRS (p = 0.455), PR (p = 0.833), but LAPs were more frequently located in the LAD (p = 0.0009). Conclusions Coronary plaques located in the RCA were more voluminous and exhibited a higher volume of lipid rich and non-calcified atheroma. However, compared to the RCA and CXA, the left anterior descending artery presented CPs with a more expressed degree of vulnerability, a higher number of vulnerability markers per plaque, and a higher incidence of LAP.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Morten K Christiansen ◽  
Jesper M Jensen ◽  
Hans Erik Bøtker ◽  
Henrik K Jensen

Introduction: A family history of premature coronary artery disease (CAD) is a well-known risk factor for adverse coronary events with age of onset being inversely related to the degree of heritability. Hypothesis: We hypothesized that asymptomatic first degree relatives, of patients with premature CAD, suffer a high burden of subclinical coronary atherosclerosis. Methods: First degree relatives, aged 30-65 years, of patients with a documented coronary revascularization procedure before the age of 40 years, were invited to participate in the study. Participants were matched by age, sex and absence of a family history, with patients referred for coronary CT angiography (CTA) because of atypical angina or non-anginal chest pain. A pooled blinded analysis was performed. The main outcome measure was the number of plaque-affected coronary segments. Results: 88 relatives and 88 symptomatic controls underwent CTA. Treatment of hypertension and dyslipidemia tended to be more common among controls (p=0.06). 4 relatives reported vague symptoms of which none had angiographic signs of obstructive CAD (any luminal stenosis above 50%). The calculated SCORE risk among relatives was generally low (85% having a 10-year risk of ≤1%). Relatives had significantly (p=0.006) more affected segments than controls (0 segments: 29,6% vs. 48,9%, 1-2 segments: 27,3% vs. 31,8%, 3-5 segments: 23,9% vs. 11,4% and ≥6 segments: 19,3% vs. 8,0%). In a multivariable logistic regression analysis, the presence of any CAD (OR 3.16 (1.50;6.70)) as well as non-calcified plaques (OR 2.2 (1.14;4.26)), mixed plaques (OR 6.77 (2.7;16.98)) and calcified plaques (OR 2.34 (1.01;5.43)) were more frequent. Although increased, the presence of obstructive plaques, however, did not differ statistically significantly between relatives and controls (OR 2.58 (0.85;7.83)). Conclusions: Asymptomatic relatives of patients with premature CAD suffer a high coronary plaque burden even when compared with symptomatic patients with an a priori higher risk of CAD. Our results indicate a strong genetic component in the genesis of coronary atherosclerosis and, moreover, underline the limitations of current guidelines on prevention of CAD.


2015 ◽  
Vol 129 (2) ◽  
pp. 93-105 ◽  
Author(s):  
Mamoru Satoh ◽  
Yuji Takahashi ◽  
Tsuyoshi Tabuchi ◽  
Yoshitaka Minami ◽  
Makiko Tamada ◽  
...  

Coronary artery disease (CAD) is the leading cause of death worldwide. The efficacy and safety of statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) in primary and secondary prevention of CAD are confirmed in several large studies. It is well known that statins have some pleiotropic, anti-atherosclerotic effects. We review the molecular mechanisms underlying the beneficial effects of statins revealed in recently published studies. Endothelial cell injury is regarded as the classic stimulus for the development of atherosclerotic lesions. In addition, the inflammatory process plays an important role in the aetiology of atherosclerosis. In particular, chronic inflammation plays a key role in coronary artery plaque instability and subsequent occlusive thrombosis. Our previous reports and others have demonstrated beneficial effects of statins on endothelial dysfunction and chronic inflammation in CAD. A better understanding of the molecular mechanism underlying the effectiveness of statins against atherosclerosis may provide a novel therapeutic agent for the treatment of coronary atherosclerosis. The present review summarizes the cellular and molecular mechanism of statins against coronary atherosclerosis.


2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Dinaldo C Oliveira ◽  
Augusto Brasileiro ◽  
Danielle Oliveira ◽  
Elayne Heide ◽  
Myrtson Gurgel ◽  
...  

Introduction: The role of the immune and inflammatory pathways in patients with atherosclerosis is important but not complete understood. The objective of this study was to evaluate if patients with coronary atherosclerosis have higher concentrations of interleukins 17 A and 22 when compared to patients without carotid atherosclerosis. Hypothesis: There are higher concentrations of interleukins 17 A and 22 in patients with coronary artery disease than in patients without carotid disease Methods: This is a cross-sectional, prospective, analytical study, conducted from August to December 2015, that enrolled 60 patients. We included 30 patients with stable CAD with coronary stenosis ≥ 50% according to current coronary angiography and 30 patients with chronic infectious parasitic disease without carotid atherosclerosis according to intimal medial thickness. Interleukins (IL) were evaluated in serum of patients. IL concentrations were expressed in pg / ml and the detectable minimum values of interleukins were: 17A = 15.62 pg/ml and 22 = 7.81 pg/ml. Descriptive and analytical statistical analyzes were performed. The Shapiro-Wilk normality test was applied to verify the normality of the data. Statistical tests were used to compare the variables and p-value < 0.05 was significant Results: There were 18 men and 12 women in the group of patients with coronary disease and 14 men and 16 patients without carotid disease. The main CAD risk factors (in the group of patients with coronary atherosclerosis) were: Hypertension 63%, Diabetes Mellitus 40%, dyslipidemia 33%, smoking 23%. The serum concentrations of interleukins 17A showed: patients with coronary atherosclerosis = 15.62 pg/ml vs patients without carotid atherosclerosis = 15.62 pg/ml. Serum concentrations of interleukins 22 showed: patients with coronary atherosclerosis = 7.81 pg/ml vs patients without carotid atherosclerosis = 7.81 pg/ml. Conclusions: Interleukin 17 and 22 concentrations were low in both groups of patients and there were no differences between patients with coronary atherosclerosis and no carotid atherosclerosis. Therefore, it is possible that these interleukins measured may not identify who has coronary atherosclerosis and who does not have carotid atherosclerosis.


2014 ◽  
Vol 55 (3) ◽  
pp. 197-203 ◽  
Author(s):  
Se-Hong Kim ◽  
Ju-Hye Chung ◽  
Beom-June Kwon ◽  
Sang-Wook Song ◽  
Whan-Seok Choi

Biology ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1139
Author(s):  
Ewelina Anna Dziedzic ◽  
Wiktor Smyk ◽  
Izabela Sowińska ◽  
Marek Dąbrowski ◽  
Piotr Jankowski

Background: Postmenopausal women experience rapid progression of coronary artery disease. Vitamin D deficiency appears to be a modifiable risk factor for cardiovascular diseases. This study aimed to analyze the impact of 25-hydroxyvitamin D3 (25(OH)D) level on the severity of coronary atherosclerosis and its potential cardioprotective effect in postmenopausal women. Material and Methods: The study prospectively recruited 351 women in postmenopausal age undergoing coronary angiography. The severity of coronary atherosclerosis was assessed using the Coronary Artery Surgery Study Score (CASSS). A level of 25(OH)D was measured with electrochemiluminescence. Results: Women with more severe coronary atherosclerosis have significantly lower 25(OH)D serum level (p = 0.0001). Vitamin D (β = −0.02; p = 0.016), hypertension (β = 0.44; p = 0.025), age (β = 0.02; p = 0.003), and history of MI (β = 0.63; p < 0.0001), were shown as CASSS determinants. Age, hyperlipidemia, and history of MI were found to determine the level of vitamin D (all p < 0.05). Women with a three-vessel disease hospitalized due to ACS, with a history of MI, hyperlipidemia and hypertension presented the lowest vitamin D level. Conclusions: Our study showed that lower serum 25(OH)D in postmenopausal women is associated with more significant stenosis in the coronary arteries. Therefore, we suggest considering low vitamin D level as a potential risk factor for coronary artery disease.


2002 ◽  
Vol 88 (12) ◽  
pp. 1020-1025 ◽  
Author(s):  
Verena Schroeder ◽  
Tushar Chatterjeel ◽  
Haresh Mehta ◽  
Stephan Windecker ◽  
Trinh Pham ◽  
...  

SummaryDue to its role in the balance between coagulation and fibrinolysis, thrombin activatable fibrinolysis inhibitor (TAFI) may be involved in the development of cardiovascular diseases. We studied 362 patients with coronary artery disease (CAD) and 134 control subjects free of CAD, both groups investigated by angiography. TAFI antigen levels were determined in venous and intracoronary plasma samples and were related to metabolic and hemostatic risk factors and extent of coronary atherosclerosis. Venous TAFI levels tended to be higher in CAD patients compared to controls, whereas this difference was significant in intracoronary samples. A subgroup of patients who had not experienced acute myocardial infarction or undergone previous cardiac interventions showed significantly higher TAFI levels in both venous and intracoronary plasma samples. TAFI levels correlated with acute phase reactants indicating a role for TAFI in inflammation. However, TAFI levels did not correlate with extent of coronary atherosclerosis and among the classical cardiovascular risk factors TAFI levels only correlated with total cholesterol and fibrinogen concentration. Our results suggest that TAFI might be a risk factor for the development of CAD.


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