Atherosclerotic Lesions In Coronary Arteries Research Articles

Relationship between free fatty acids, insulin resistance markers, and oxidized lipoproteins in myocardial infarction and acute left ventricular failure

BackgroundThe most common cause of myocardial infarction (MI) is stenotic atherosclerotic lesions in subepicardial coronary arteries. Artery disease progression induces clinical signs and symptoms, among which MI is the leader in mortality and morbidity. Recent studies have been trying to find new biochemical markers that could predict the evolution of clinical complications; among those markers, free fatty acids (FFA) and oxidative modification of low-density lipoproteins (oxidized LDL) have a special place.Materials and methodsSeventy-nine ST-elevation MI patients were enrolled. The first group included MI patients without the signs of acute heart failure (Killip class I) while MI patients with Killip classes II–IV made up the second group. Thirty-three individuals with no cardiovascular disease were the controls. The lipid profile, serum oxidized LDL, and their antibodies, C-peptide and insulin were measured at days 1 and 12. The level of insulin resistance was assessed with the quantitative insulin sensitivity check index (QUICKI).ResultsMI patients had atherogenic dyslipidemia; however, the Killip II–IV group had the most pronounced and prolonged increase in FFA, oxidized LDL, and their antibodies. Additionally, positive correlations between FFA levels and creatine kinase activity (12 days, R = 0.301; P = 0.001) and negative correlations between the QUICKI index and FFA levels (R = −0.46; P = 0.0013 and R = −0.5; P = 0.01) were observed in the both groups.ConclusionThe development of MI complications is accompanied by a significant increase in FFA levels, which not only demonstrate myocardial injury, but also take part in development of insulin resistance. Measuring FFA levels can have a great prognostic potential for risk stratification of both acute and recurrent coronary events and choice of treatment strategy.

Concentration of vascular endothelial growth factor in patients with acute coronary syndrome

Vascular endothelial growth factor (VEGF) is a regulator of vascular formation in physiological and pathological conditions. The aim of our study was to evaluate the value of VEGF as a surrogate marker of myocardial injury in acute ischemic conditions. Materials and methodsIn 104 consecutive patients with acute coronary syndrome (ACS) with and without ST segment elevation (STEMI and NSTEMI) the plasma and serum human VEGF (hVEGF) concentration was measured two times i.e. immediately after admission due to ACS and 24h later. According to ECG findings and coronary angiography results, patients were divided into three groups. Group A represented major myocardial injury due to ST-segment elevation in precordial leads and/or in I and aVL leads and with left anterior descending (LAD) artery responsible for STEMI symptoms or additionally with significant atherosclerotic lesions (lumen vessel narrowed>50%) in other than LAD coronary arteries. Group B (medium myocardial injury) consisted of patients with ST-segment elevation in II, III and aVF leads and/or ST-segment depression in V2-V3 leads with one-vessel disease and the culprit artery was not LAD. Group C included patients with changes in ECG other than ST-segment elevation independently of the site of atherosclerotic lesions in coronary arteries. ResultsIn all 104 patients with ACS the highest values of serum hVEGF were observed in second measurement (357.9±346 pg/ml, p<0.01). Although in the first measurement, plasma and serum hVEGF concentration did not differentiate groups, the difference between deltas for serum hVEGF was observed (p<0.05). Increased number of neutrophils in the first measurement increased the OR of the high serum hVEGF concentration in the first measurement (OR=1.155; 95%CI: 1.011; 1.32) (p<0.05). The number of neutrophils in the second measurement also revealed significant relationship with high serum hVEGF in the first assessment (OR=1.318, 95%CI: 1.097; 1.583) (p<0.01). Increased values of triglycerides (exceeding the upper limit) were connected with decreased OR of high serum hVEGF concentrations in the first measurement (OR=0.152, 95%CI: 0.033; 0.695, p<0.05). ConclusionsIn acute coronary syndrome, serum VEGF concentrations are elevated and can serve as a surrogate marker of myocardial injury. The elevated number of neutrophils increases odds ratio of high VEGF concentrations in ACS. In patients with high concentrations of triglycerides, odds ratio of low level of hVEGF is expected.

Study of Coronary Atherosclerosis by Modified American Heart Association Classification of Atherosclerosis-An Autopsy Study

The study was designed to assess the atherosclerotic lesions in coronary arteries in cases subjected to autopsy to grade by applying Modified American Heart Association (AHA) classification, evaluate the atheromatous & vulnerable plaques to find out the to age and sex related prevalence of atherosclerosis in the semi-urban & urban population of Jamnagar, a district in Western India. Autopsy was conducted on 264 cases whose age ranged from 8-79 years, by the conventional technique; heart was removed & dissected along the direction of blood flow. Microscopic assessment of the three main coronary arteries was done. According to Modified AHA classification of atherosclerosis, maximum number of cases were in the 40-49 years age group. Intimal xanthoma was the most common type in all three coronary arteries. The number of males was 168(64%) and females was 96(36%). 59% males & 52% female were affected from atherosclerosis. An intermediate lesion was noted commonly in young individuals (10-39 years) and older individuals (40-79 years) were 46% & 41% respectively. Pathological Intimal thickening was more common in left anterior descending coronary artery compared to others. Thin fibrous cap atheroma was more common in Left circumflex artery than compared to Left anterior descending artery & Right coronary artery. The study highlights the impact of atherosclerotic lesions in the population of Jamnagar, a district in Gujarat state of Western India. The increased amount of intermediate atherosclerotic lesions found in the young population gives an indication that anti-atherogenic preventive measures and drastic dietary & life style modification need to be implemented in young individuals, this will help to prevent coronary artery disease from causing premature death that lead to huge financial burden on the economy and health sector of India.

Tissue inhibitor of matrix metalloproteinases 4 (TIMP4) in a population of young adults: Relations to cardiovascular risk markers and carotid artery intima-media thickness. The Cardiovascular Risk in Young Finns Study

Objectives. The tissue inhibitor of metalloproteinases 4 (TIMP4) is present in significant amounts in human atherosclerotic coronary artery lesions, but its relations with the early pathogenesis of atherosclerotic changes have not been clarified. We studied the associations of circulating TIMP4 with pre-clinical markers of atherosclerosis and traditional cardiovascular risk factors by using longitudinal data on carotid artery intima-media (cIMT) thickness in a population-based cohort of asymptomatic young adult Finns. Methods. Data on cIMT, plasma TIMP4, lipids, CRP, blood pressure, BMI, smoking status and daily alcohol intake were obtained from 980 24–39 year-old participants in 2001. The 6-year follow-up in cIMT measurements were performed in 2007 for 769 participants. Results. Plasma TIMP4 concentrations (mean ± SD) were 2.3 ± 1.7 ng/mL in men and 2.5 ± 1.8 ng/mL in women. Age, LDL-cholesterol, BMI and systolic blood pressure were directly associated with TIMP4 concentration. In a multivariable model, the independent determinants of TIMP4 included systolic blood pressure (p = 0.008) and daily smoking (p = 0.009), both being inversely associated with TIMP4. These two baseline variables explained 1.5% of the variation in TIMP4. TIMP4 was significantly and inversely associated with cIMT measured 6 years later (beta =− 0.0135, p = 0.01) explaining 0.7% of the variability of cIMT. Conclusion. In young apparently healthy adults, circulating TIMP4 concentration was independently and inversely associated with cIMT, a marker of vascular structure and function.

Количественный анализ некоторых групп микроорганизмов, выделенных из атеро-склеротически изменённых коронарных артерий больных в зависимости от ASP299GLY полиморфизма гена TLR4

The estimation data of contamination by separate groups of microorganisms and dependence of the microbial content level upon TLR4 gene 896A/G polymorphism in 20 samples of atherosclerotic lesions in coronary arteries has been presented. The presence of TLR4 gene polymorphic allele G in the individual genotype determines the increased contamination of atherosclerotic plaque tissues by the representatives of the following genera: Lactobacillus sp., Enterobacterium sp., Sneathia sp. /Leptotrihia sp. /Fusobacterium sp., Mobiluncus sp. /Corynebacterium sp., Peptostreptococcus sp. The emergence of new correlation pairs with participation of Lachnobacterium sp. /Corynebacterium sp. among the carriers of G allele has been revealed via the intragroup correlation analysis. The obtained results confirm the possible involvement of the represented groups of microorganisms in the pathogenesis of atherosclerosis and the role of the TLR4 gene polymorphic variant G in the increased microbial contamination of the coronary arteries tissues.

Force-specific activation of Smad1/5 regulates vascular endothelial cell cycle progression in response to disturbed flow

Vascular endothelial cells (ECs) are constantly exposed to blood flow-induced shear stress, but the mechanism of force-specific activation of their signaling to modulate cellular function remains unclear. We have demonstrated that bone morphogenetic protein receptor (BMPR)-specific Smad1/5 can be force-specifically activated by oscillatory shear stress (OSS) in ECs to cause cell cycle progression. Smad1/5 is highly activated in ECs of atherosclerotic lesions in diseased human coronary arteries from patients with end-stage heart failure undergoing heart transplantation and from apolipoprotein E-deficient mice. Application of OSS (0.5 ± 4 dyn/cm(2)) causes the sustained activation of Smad1/5 in ECs through activations of mammalian target of rapamycin and p70S6 kinase, leading to up-regulation of cyclin A and down-regulations of p21(CIP1) and p27(KIP1) and, hence, EC cycle progression. En face examination of rat aortas reveals high levels of phospho-Smad1/5 in ECs of the inner, but not the outer, curvature of aortic arch, nor the straight segment of thoracic aorta [corrected]. Immunohistochemical and en face examinations of the experimentally stenosed abdominal aorta in rats show high levels of phospho-Smad1/5 in ECs at poststenotic sites, where OSS occurs. These OSS activations of EC Smad1/5 in vitro and in vivo are not inhibited by the BMP-specific antagonist Noggin and, hence, are independent of BMP ligand. Transfecting ECs with Smad1/5-specific small interfering RNAs inhibits the OSS-induced EC cycle progression. Our findings demonstrate the force-specificity of the activation of Smad1/5 and its contribution to cell cycle progression in ECs induced by disturbed flow.

Vein graft failure: current clinical practice and potential for gene therapeutics

Autologous saphenous vein is commonly used as a conduit to bypass atherosclerotic lesions in coronary and femoral arteries. Despite the wide use of arterial conduits, which are less susceptible to complications and failure, as alternative conduits, the saphenous vein will continue to be used in coronary artery bypass grafting until acceptable alternative approaches are evaluated. Hence, preservation of vein graft patency is essential for the long-term success. Gene therapy is attractive in this setting as an ex-vivo technology to genetically manipulate the conduit before grafting. The use of safe and efficient vectors for delivery is a necessity as well as a strategy to improve patency in the long term. Here, we review the current clinical practice, the pathogenesis of bypass graft failure and adenovirus-mediated gene therapy strategies designed to improve late vein graft failure by modulation of smooth muscle cells in the vein wall.

Lipasa endotelial y su relación con la enfermedad cardiovascular y diabetes mellitus tipo 2

Endothelial lipase (EL) is synthetized by endothelial cells and its main substrates are lipoprotein phospholipids. Over expression of EL reduces high density lipoprotein (HDL) cholesterol and phospholipids, in vivo and in vitro. Inhibition of the enzyme achieves the opposite effects. The synthesis of the enzyme is regulated by interleukin 1 and tumor necrosis factor a. These inflammatory cytokines play a role in diabetes and vascular disease. An increase in vascular mechanical forces, that play a role in atherogenesis, also increase the synthesis of EL. There is expression of EL in endothelial cells, macrophages and muscle cells of atherosclerotic lesions of coronary arteries of humans. This evidence leads to the suspicion that EL plays a role in atherogenesis. There are also higher plasma levels of EL in subjects with type 2 diabetes, who are especially susceptible to the development of vascular lesions. Therefore the inhibition of EL could play an important role in HDL metabolism and could be a new therapeutic strategy for the prevention of atherosclerosis.

The number of cells and the cell proliferation in intima of various human arteries

Increased cell proliferation at the early stages of an atherosclerotic lesion is considered an important stage of development of this pathology, but the degree of the proliferation at various stages of formation of atherosclerotic plaque in various human large arteries so far has been studied insufficiently. In the present work, we studied the thickness of intima and proliferation of the newly “infiltrated” hematogenic and resident cells in atherosclerotic lesion of carotid and coronary arteries; a comparison is also made with similar results obtained on the aorta and presented in our earlier publications. Analysis of thickness of intima and of proliferation in normal intima and at various stages of atherosclerotic lesion (initial stages, lipid strips, lipofibrous plaques, fibrous plaques) showed that, in spite of similar tendencies toward changing the level of infiltration of hematogenic cells and proliferation in various types of arteries, there exist significant quantitative differences between various types of arteries. Thus, it is found that hematogenic cells in lipofibrous plaques of coronary and carotid arteries account for one-third and almost half of the total cell population, respectively, whereas the atherosclerosis-lesioned sites of the aorta, as we showed earlier, contain no more than 15% of hematogenic cells. This allows one to think that the contribution of hemopoietic cells to development of atherosclerosis in carotid and coronary arteries is greater than in the aorta. In spite of differences in the number of the hemopoietic cells accumulating in intima, an analogous bell-shaped dependence of the number of cells on the type of lesion (in the sequence normal intima-initial stages of pathology-lipid strips-lipofibrous plaques-fibrous plaques) was shown for coronary and carotid arteries. Visualization of proliferating (PCNA-positive) cells in atherosclerosed and normal (unchanged) zones of coronary and carotid arteries revealed a similar picture. The maximum number of PCNA-positive resident cells was found in lipofibrous plaques. Changes of the total number of cells were accompanied by a change in the number of proliferating resident and proliferating hematogenic cells.

Matrix Metalloproteinase 13 Genotype in rs640198 Polymorphism Is Associated with Severe Coronary Artery Disease

Atherosclerosis as a main etiopathogenetic source for coronary artery disease (CAD) development is intimately related to dynamic changes in the extracellular matrix (ECM). Elevated levels of MMP-13 have been observed in human atherosclerotic plaques which could also involve variability in MMP-13 gene. The aim of the study was to associate rs640198 polymorphism with CAD and/or with its severity.The study comprised 1071 consecutive patients with suspected or known coronary artery disease (CAD), confirmed by coronary angiography.Genotyping for the rs640198 polymorphism in MMP-13 gene was performed using Taqman® assay. The TT and TG genotypes of rs640198 polymorphism in MMP-13 gene confer the significantly increased risk of triple vessel disease compared to patients without atherosclerotic lesions in coronary arteries (odds ratio = 1.64, Pcorr = 0.05). Furthermore, an increased risk of having 5 and more stenoses (odds ratio = 1.90, Pcorr = 0.004) was observed in TT and TG carriers (sensitivity of 0.613 and a specificity of 0.544; power of the test is 0.87).The T allele of MMP-13 intron polymorphism rs640198 is associated with the severity of coronary artery disease, represented by the number of affected arteries as well as by the number of stenoses confirmed by coronarography.

Matrix metalloproteinase 13 genotype in rs640198 polymorphism is associated with severe coronary artery disease.

Atherosclerosis as a main etiopathogenetic source for coronary artery disease (CAD) development is intimately related to dynamic changes in the extracellular matrix (ECM). Elevated levels of MMP-13 have been observed in human atherosclerotic plaques which could also involve variability in MMP-13 gene. The aim of the study was to associate rs640198 polymorphism with CAD and/or with its severity.The study comprised 1071 consecutive patients with suspected or known coronary artery disease (CAD), confirmed by coronary angiography.Genotyping for the rs640198 polymorphism in MMP-13 gene was performed using Taqman® assay. The TT and TG genotypes of rs640198 polymorphism in MMP-13 gene confer the significantly increased risk of triple vessel disease compared to patients without atherosclerotic lesions in coronary arteries (odds ratio = 1.64, Pcorr = 0.05). Furthermore, an increased risk of having 5 and more stenoses (odds ratio = 1.90, Pcorr = 0.004) was observed in TT and TG carriers (sensitivity of 0.613 and a specificity of 0.544; power of the test is 0.87).The T allele of MMP-13 intron polymorphism rs640198 is associated with the severity of coronary artery disease, represented by the number of affected arteries as well as by the number of stenoses confirmed by coronarography.

The influence of obesity on progression of coronary arteriosclerosis and clinical course after ST elevation acute myocardial infarction treated with primary coronary interventions

Evaluation of influence of obesity on the coronary atherosclerosis development and clinical outcome in patients with STEMI treated by PCI with BMS implantation. 82 patients (64 men) treated with PCI within 6 hours from 1st STEMI. Three groups of pts were formed according to BMI. Based on coronary angiography number of significant stenoses (NSS), number of stenosed coronary arteries (NSA), and sum of significant stenoses (SSS) were calculated. Echocardiography examination was performed 3 days and 6 months after STEMI. Serial evaluation of TnI, CK, CKMB was performed after admission, and serum BNP was assessed after 2 days, 1 and 6 months after STEMI. Obese patients revealed higher values of NSA, NSS and SSS than patients with normal BMI and overweight. There were no differences of BNP, maximal values and AUC of CK, CKMB, TnI and echocardiographic parameters between all groups whereas decrease of BNP during follow-up correlated with BMI. Results of our prospective study indicate that in obese patients, there is a significantly greater number of atherosclerotic lesions in coronary arteries found during PCI, as compared to those with normal body weight or overweight. We proved that overweight and obesity did not result in significantly greater damage to the myocardium and left ventricular dysfunction, both in the acute phase and 6 months after myocardial infarction treated with primary coronary intervention, as compared to those with normal body weight. In addition correlation was found between BNP concentration profile and body mass index in the 6-month follow-up after STEMI treated with PCI and bare metal stent implantation.

Review: Role of cerebral vessels in ischaemic injury of the brain

This review discusses the pathological changes in the heart and vessels underlying brain ischaemic injury, with a major focus on atherosclerotic disease of the brain induced by lesions of the extracranial cervical and major intracranial arteries and small-vessel disease of the brain. The carotid bifurcation is the primary site for atherosclerotic changes, for which extensive clinical trials and pathological analyses on carotid endarterectomy specimens have been performed. Plaque rupture and erosion give rise to thrombus formation, which leads to brain ischaemic injury. These changes have much in common with atherosclerotic lesions of the subepicardial coronary arteries. Emboli of various types of particles are characteristics of brain ischaemic injury. Thrombi rich in fibrin and red blood cells (red thrombi) that develop in the cardiac chambers are common sources of cerebral emboli. Small-vessel disease of the brain induces fibrinoid necrosis, microaneurysm, fibrohyalinosis, lipohyalinosis and microatheroma, changes commonly associated with hypertension. The acute hypertensive small-vessel changes organize to create segmental arterial disorganization and deep small infarcts when they escape from rupture. Some specific vascular diseases responsible for brain ischaemic injury are briefly reviewed also.

Localization of Latent Transforming Growth Factor-.BETA. Binding Protein-1 in Human Coronary Atherosclerotic Plaques

Transforming growth factor-β (TGFβ) and its receptors have been detected by immunohistochemistry in the normal vessel wall and in atherosclerotic lesions of human coronary arteries. However, TGFβ is normally secreted as an inactive complex associated with a latent TGFβ-binding protein (LTBP). Therefore, detection of TGFβ antigen only in the arterial wall does not imply the activated form of the growth factor. In situ hybridization and immunohistochemistry demonstrated LTBP1 mRNA and protein expression throughout the media and intima of early coronary artery lesions, with the highest levels of protein at the luminal surface. In advanced lesions, LTBP1 mRNA and protein were detected mainly in regions of high cell density, such as the fibrous cap. Assays of the TGFβ signalling pathway will be required to determine the activity associated with TGFβ antigen in the vessel wall.

Peculiarities of cell composition and cell proliferation in different type atherosclerotic lesions in carotid and coronary arteries

Increased cell proliferation in early atherosclerotic lesions is recognized as an essential event in atherogenesis but the levels of cell proliferation in the different stages of atherosclerotic plague formation in different types of human large arteries are still insufficiently studied. In the present work, we studied intima thickness and proliferation of newly “infiltrated” hematogenous and resident cells in atherosclerotic lesions of the carotid and coronary arteries and compared these parameters with those in the aorta, which we reported in an earlier publication (Orekhov et al. [8]). Analysis of intima thickness and proliferation in grossly unaffected intima and in different types of atherosclerotic lesions (initial lesions, fatty streaks, lipofibrous plaques, and fibrous plaques) revealed that, although there were similar tendencies in the change of the infiltration levels of hematogenous cells and proliferation in different types of arteries, there were significant quantitative differences between different types of arteries. Hematogenous cells in lipofibrous plaques of the coronary and carotid arteries were found to account for a third and almost for a half of the total cell population, respectively, while atherosclerotic lesions in the aorta, as shown by us previously, contain no more than 15% of hematogenous cells. This suggests that the contribution of hematogenous cells to the development of atherosclerosis in the carotid and coronary arteries appears to be more significant than in the aorta. Despite the differences in the numbers of accumulating hematogenous cells in the intima, a similar “bell-shaped” dependence of cell numbers on the lesion type, involved the following sequence: unaffected intima – initial lesions – fatty streaks – lipofibrous plaques – fibrous plaques, was detected in the coronary and carotid arteries. The visualization of PCNA-positive cells in atherosclerotic and unaffected zones of the coronary and carotid arteries revealed similar patterns of the distribution of proliferating cells. The maximum numbers of PCNA-positive resident cells were identified in lipofibrous plaques. The changes in the total cell numbers were found to be accompanied by the changes in the numbers of both proliferating resident cells and proliferating hematogenous cells. According to our knowledge, this is the first report that provides factual data about the similarities and differences in cell composition and proliferation between different types of large arteries in which the development of atherosclerosis is of crucial importance.

Rationale and Design of a Randomized Clinical Comparison of Everolimus-Eluting (Xience V/Promus) and Sirolimus-Eluting (Cypher Select+) Coronary Stents in Unselected Patients with Coronary Heart Disease

Background: The sirolimus-eluting stent has demonstrated the least amount of late lumen loss among previously released drug-eluting stents, but its safety and efficacy has not been compared head-to-head with the everolimus-eluting stent. Method: The Scandinavian Organization for Randomized Trials with Clinical Outcome (SORT OUT) IV trial was designed as a prospective, multi-center, open-label, all-comer, two-arm, randomized, non-inferiority study comparing the everolimus-eluting stent with the sirolimus-eluting stent in the treatment of atherosclerotic coronary artery lesions. Based on a non-inferiority design, power calculations estimated a needed enrolment of 2,678 patients. The primary endpoint is a composite of cardiac death, myocardial infarction, and stent thrombosis or target vessel revascularization after 9 months. Data on clinical events and mortality for all randomized patients will be obtained from national databases at 9 months. No clinical follow-up examination is scheduled. Conclusion: The SORT OUT IV trial will directly compare clinically relevant differences in efficacy and safety in two drug-eluting stents: a first-generation sirolimus-eluting stent versus a second-generation everolimus-eluting stent. The study makes use of clinical endpoints routinely collected in computerized healthcare registries, allowing complete follow-up of a large, well-defined population without scheduled angiographic examinations.

Risk of atherosclerotic disease coronary artery lesions in childhood cancer survivors.

e19586 Background: Increases in several traditional risk factors for atherosclerotic disease (AthD) such as cholesterol may partially explain the recently documented increased incidence of early cardiovascular disease (CVD) in survivors. The ability to aggregate these traditional risk factors into a single measure of AthD risk may not only help identify the cause of increased early CVD in survivors but also improve the interpretation of traditional risk factor testing. This has recently become possible using the NIH Pathobiological Determinants of Atherosclerosis Study's risk scoring system (PDAY) that predicts risk of an AthD coronary artery lesion in 15- to 34-yr olds. Methods: Risk factors were measured in a representative sample of 101 survivors and 31 siblings from 15-34 yrs old in an NCI prospective cohort study in Rochester, NY from 1999-2004. Risk factors were aggregated using PDAY, a weighted combination of age, sex, total cholesterol, HDL-cholesterol, smoking, systolic BP, hyperglycemia, and BMI. Survivors were compared to siblings after adjusting for age and sex. Results: Survivors were a mean 14 yrs from diagnosis; 57% received anthracyclines, 41% cardiac radiation, 48% cranial radiation, and 5% total body radiation as part of multiagent therapy. Survivors had similar AthD lesion risk as siblings (p = .83) which increased for males and by age. Conclusions: Similar estimates of AthD risk between survivors and siblings suggests much of the increase in early CVD incidence observed in follow-up studies of survivors is due to the direct effects of cancer treatment such as radiation exposure. Total CVD risk is a combination of this increased risk and that due to traditional risk factors. PDAY provides clinicians caring for survivors a new easy to use and cost free tool to assess the latter. Thus, PDAY may improve survivorship care by increasing understanding of how traditional AthD risk factors predispose to future CVD, identifying survivors requiring further assessment, and hopefully increasing compliance with risk reduction strategies. Mean (range) PDAY risk estimate of AthD lesions for survivor subgroups 15-24-yr-old females 15-24-yr-old males 25-34-yr-old females 25-34-yr-old males <1% (0-8%) 3% (0-24%) 9% (3-26%) 18% (7-42%) No significant financial relationships to disclose.

Call for Standards in Technical Documentation of Intracoronary Stents

At present, the product information of intracoronary stents provided by the industry contains only limited technical data restricting judgments on the in vivo performance of individual products. Available experimental and clinical evidence suggests that interventional target sites display highly heterogeneous biomechanical behavior needed to be matched by specific stent and stent delivery system characteristics. To allow individualized stent-lesion matching, both, understanding of biomechanical properties of the atherosclerotic coronary artery lesions and expert knowledge of the intracoronary stent systems, are required. Here, the authors review some of the initial data on mechanical properties of coronary artery lesions potentially relevant to stenting and suggest standards for technical documentation of intracoronary stents.

Fibulin-1 and fibrinogen in human atherosclerotic lesions

Fibulin-1 is a fibrinogen-binding blood protein and a component of many extracellular matrices (ECM) including those of blood vessels. In this study, the deposition patterns of fibulin-1 and fibrinogen were examined in human coronary artery atherosclerotic lesions excised by atherectomy from 20 patients. Fibulin-1 deposition was found to be closely overlapping with fibrinogen located within the atherosclerotic lesions and in regions containing fresh thrombi. Pronounced intracellular fibulin-1 immunostaining was apparent in lesion areas rich in macrophages and foam cells, although THP-1 macrophages and foam cells were found not to express fibulin-1. Strong ECM deposition of fibulin-1 was observed in acellular atheromatous and myxomatous regions. By contrast, fibulin-1 was present at relatively low levels in the ECM associated with smooth muscle cells within and outside of lesions and was not detected in sclerotic regions. These results reveal the pattern of fibulin-1 within human atherosclerotic lesions and highlight the potential for fibulin-1, perhaps derived from the blood and acting in conjunction with fibrinogen, to play a role in the etiology and cardiovascular disease progression, particularly with respect to thrombotic aspects of atherosclerosis.

Mesenchymal stem cells-derived vascular smooth muscle cells release abundant levels of osteoprotegerin.

Although several studies have shown that the serum levels of osteoprotegerin (OPG) are significantly elevated in patients affected with atherosclerotic lesions in coronary and peripheral arteries, the cellular source and the role of OPG in the physiopathology of atherosclerosis are not completely defined. Therefore, we aimed to investigate the potential contribution of mesenchymal stem cells in the production/release of OPG. OPG was detectable by immunohistochemistry in aortic and coronary atherosclerotic plaques, within or in proximity of intimal vascular smooth muscle cells (SMC). In addition, bone marrow mesenchymal stem cell (MSC)-derived vascular SMC as well as primary aortic SMC released in the culture supernatant significantly higher levels of OPG with respect to MSC-derived endothelial cells (EC) or primary aortic EC. On the other hand, in vitro exposure to full-length human recombinant OPG significantly increased the proliferation rate of aortic SMC cultures, as monitored by bromodeoxyuridine incorporation. Taken together, these data suggest that OPG acts as an autocrine/paracrine growth factor for vascular SMC, which might contribute to the progression of atherosclerotic lesions.