Localization Of Atherosclerotic Lesions Research Articles

Association of Smoking, Diabetes, and Dialysis with the Presence of Popliteal Lesions in Femoropopliteal Artery Disease.

Although recent advances in endovascular devices have markedly improved clinical outcomes of femoropopliteal endovascular therapy, lesions located in the popliteal artery are still a major challenge. This study aimed to determine the association of cardiovascular risk factors, including smoking, diabetes mellitus, and dialysis-dependent renal failure, with the location of atherosclerotic lesions in femoropopliteal artery disease. We used a multicenter prospective study database registering patients with symptomatic femoropopliteal artery disease undergoing drug-coated balloon treatment. The analysis included 1912 patients with de novo femoropopliteal lesions. The association of clinical characteristics with popliteal lesions was investigated using the logistic regression model. In addition, the femoropopliteal artery was divided into six segments (the proximal, middle, and distal portions of the superficial femoral artery and P1, P2, and P3 segments of the popliteal artery), and the association of clinical characteristics with the presence of atherosclerotic lesions in the respective arterial segments was investigated. Smoking and dialysis-dependent renal failure showed a statistically significant inverse and positive association with the presence of popliteal lesions, respectively (adjusted odds ratio, 0.66 [95% confidence interval, 0.51-0.85] and 2.01 [1.62-2.49]; P=0.001 and P＜0.001), whereas diabetes mellitus did not (P=0.17). The subsequent per-segment analysis presented similar results. Smoking was inversely associated with popliteal lesions, whereas renal failure on dialysis was positively associated in patients with symptomatic femoropopliteal artery disease who underwent drug-coated balloon treatment. Diabetes mellitus was not significantly associated.

Abstract 10435: Blood Flow Patterns Regulate Efferocytosis in Endothelia Cells

Introduction: Flowing blood generates a frictional force called shear stress that plays an important role in endothelial dysfunction and atherosclerosis. The disturbed flow (d-flow) pattern causes the preferential localization of atherosclerotic lesions, while regions with steady laminar flow (s-flow) are protected against atherosclerosis. Efferocytosis is a process by which apoptotic tissue is recognized for engulfment by phagocytic cells. Defective efferocytosis promotes advanced atherosclerosis. Hypothesis: We hypothesized that blood flow patterns regulate EC efferocytosis and subsequent endothelial dysfunction and contribute to the development of atherosclerosis. Methods: Primary human aortic ECs (HAECs) were exposed to s-flow and d-flow in a step-flow channel, and the changes of efferocytosis receptors in ECs and endothelial dysfunction were investigated. To investigate whether defective efferocytosis plays a role in endothelial dysfunction, HAECs were transfected with a control plasmid or MerTK CRISPR/Cas9 knockout plasmid. Results and Conclusions: Our results showed that efferocytosis regulators, such as Gas6, Pros1, and MerTK, were upregulated under s-flow conditions while inhibited under d-flow conditions compared to static conditions. Our data also showed that MerTK knockout decreased expression of VE-cadherin and CD31, while increased expression of Snail, Slug, and Twist1 as well as α-SMA, N-cadherin, calponin, and FSP1. Of note, VE-cadherin is a strictly endothelial-specific adhesion molecule located at junctions between ECs. As expected, our data showed that MerTK knockout markedly inhibited VE-cadherin expression, indicating that defective efferocytosis increases endothelial barrier dysfunction. This indicates that MerTK-mediated defective efferocytosis in ECs may play an important role in arterial areas exposed to d-flow where prone to atherosclerosis.

THE RELATIONSHIP BETWEEN THE EXPRESSION LEVELS OF TISSUE INHIBITOR OF METALLOPROTEINASES-3 (TIMP3) AND SEVERITY OF ATHEROSCLEROSIS

Objective: TIMP3 is one of tissue inhibitors of metalloproteinases (TIMPs), which binds to the components of the extracellular matrix, and has crucial roles in atherosclerogenesis and adipose tissue differentiation. In this study, it was aimed to determine the effects of TIMP3 gene expression levels on severity of atherosclerosis in different tissues. Material and Methods: The first group of the study (evaluated for coronary artery disease) were cases classified as high and low plaque scores according to the degree and location of atherosclerotic lesions. In the second group (post-mortem cases) were male cadavers who died due to coronary heart disease (CHD, n=26) and non-cardiac trauma (T-nonP, n=4). The TIMP3 expression levels were examined in leukocyte and peri-coronary epicardial adipose tissues (EAT) samples (n=69 and n=34, respectively) of the first group and EAT and coronary artery samples (n=12 and n=30, respectively) of the second group using quantitative RT-PCR. In addition, the protein expressions of TIMP3 were analysed on artery sections by immunofluorestaining. Results: In the post-mortem study group, the TIMP3 expression levels were found to increase in no plaque segments of arteries of cases with CHD (CHD-nonP) compared to advanced atherosclerotic arteries (CHD-P) and normal arteries of T-nonP cases (p=0.01 and p=0.05, respectively). The TIMP3 expressions in EATs and leukocytes were not statistically significant between the study groups. In addition, TIMP3 protein was detected in normal arteries, peri-coronary EATs and mostly in macrophages-rich areas in advanced atherosclerotic arteries. Conclusion: TIMP3 expression levels increase in normal coronary arterial segments of cases with CHD, which depict a protective role of TIMP3 in development of atherosclerosis.

Effect of Coronary Artery Bifurcation Angle on Atherosclerotic Lesion Localization Distance to the Bifurcation Site.

ObjectivesAlthough percutaneous coronary interventions become a common treatment modality for coronary artery diseases, lesion localization make these procedures more complex. As the lesion localizes near to the bifurcation site, more complex PCI procedures, overqualified equipments are needed and complication risk increases. Previous studies have demonstrated the strong correlation between wide angulation and significant coronary stenosis. However, a paucity of data exists about the association between bifurcation angle and lesion localization distance. In this study we analysed the effect of coronary bifurcation angle and left main coronary artery length on the atherosclerotic lesion localization.MethodsPatients, who underwent coronary angiography between 01.01.2017- 31.12.2019 were scanned. Patients having atherosclerotic lesions causing more than 50% luminal narrowing and Medina classification score (0,0,0) were evaluated. After exclusion, 467 patients were included. 5 bifurcation subgroups (LAD-CX, LAD-Dx, CX-OM, RCA-RV, RPD-RPL) were formed. Distance of lesion to the bifurcation site, bifurcation angle and left main coronary artery length were analysed by 2 experienced cardiologists with invasive quantitaive coronary angiography (QCA) by using “extreme angio and cardiac pacs” software system.ResultsThere was a strong inverse correlation between bifurcation angle and lesion localization distance to the bifurcation site (r = −0.706; p < 0.0001). There was a nonsignificant negative correlation between Left-main coronary artery length and lesion localization. Regression analysis revealed that bifurcation angle is an independent risk factor for predicting the localization of an atheroslerotic lesion in 5 mm length from the point of bifurcation site (β = −0.074, p < 0.0001). A cut-off value of 80.5° coronary bifurcation angle was found to have 84.1% sensitivity and 81.3% specificity in prediction of atherosclerotic lesion localization in 5 mm length from the point of bifurcation site.ConclusionIn this study we showed that as the bifurcation angle increases, atherosclerotic lesions tend to approach to the bifurcation site. Since invertentions encompassing bifurcation sites are more complex, lesions with increased angulation may need extra care as they are more likely to present with further complications. Furthermore, bifurcation angle is an independent risk factor for lesion localization.

Hybrid coronary computed tomography angiography and positron emission tomography myocardial perfusion imaging in evaluation of recurrent symptoms after coronary artery bypass grafting.

Recurrent chest pain after coronary artery bypass grafting (CABG) poses a diagnostic challenge. We hypothesized that combining anatomy of bypass grafts and native coronary arteries with ischaemia detection by hybrid imaging could be used to gain valuable and complementary information in patients with recurrent symptoms after CABG. We analysed 36 consecutive patients (67 ± 9 years, 81% male) who had undergone hybrid imaging using coronary computed tomography angiography (CCTA) and [15O]H2O positron emission tomography (PET) myocardial perfusion imaging due to recurrent symptoms after CABG. Coronary tree and left ventricular myocardium were divided into three main territories, yielding a total of 108 coronary territories in 36 patients. The presence of obstructive (≥50%) stenosis and the patency of grafts were evaluated by CCTA, while myocardial ischaemia was assessed by quantitative adenosine-stress PET. Altogether 28 (78%) of the 36 study patients presented with matched PET/CCTA abnormalities. Forty-one coronary territories were supplied by non-obstructed bypass grafts or native coronary arteries (protected territory). However, 12 (29%) of these presented with a perfusion defect. In six cases, the perfusion defect involved myocardium distal to the graft-coronary anastomosis, as interpreted on the PET/CCTA fusion images. In turn, in 48 coronary territories the supplying artery was obstructed on CCTA (unprotected territory). Of these, 41 (85%, P < 0.001 vs. protected) presented with abnormal perfusion, involving myocardium distal to the anastomosis in 29 cases. Hybrid imaging provides complementary information on the presence and localization of atherosclerotic lesions and myocardial perfusion abnormalities in symptomatic patients with previous CABG.

Specific Characteristics of Coronary Atherosclerosis

In this review, we present modern aspects of etiology and pathogenesis of atherosclerosis. We describe the roles played by inflammatory cells, components of cellular response in allergic reactions, disturbances of carbohydrate metabolism, cellular aging, and infection at various stages of formation of atherosclerotic plaques. Special attention is given to the specific characteristics of atherosclerosis and calcification of coronary arteries. We show the influence of age and gender on the disease progression. The review includes information on the importance of myocardial bridges for the change of hemodynamics in segments of coronary arteries. The data presented indicate that differences in localization of atherosclerotic lesions between systems of the right and left coronary arteries depends on their hemodynamic, anatomical and physiological characteristics. According to the literature, anterior descending artery is more vulnerable in this respect.

Endothelial dysfunction in patients with hypertension and peripheral artery disease

Aim. To assess endothelial function in patients with hypertension and peripheral artery disease.Methods. The study included 100 patients with an established diagnosis of essential hypertension. Ultrasonic duplex scanning of brachiocephalic arteries and lower limb arteries was performed. The functional state of the endothelium was evaluated using postocclusive reactive hyperemia test by D.S. Celermajer.Results. Atherosclerotic plaques in the carotid arteries were found in 71% of patients, in the lower limb arteries - in 60%. The combined affection of both vascular beds was diagnosed in 51% of patients. Endothelial dysfunction was found in 64% of patients. In patients with carotid arterial system atherosclerosis, brachial artery dilation response was 6.1%, while in those with intact carotid arteries - 4.7% (p=0.041). The value of the brachial artery dilation response in patients with atherosclerotic lesions of lower extremities arteries was 5.9%. In the subgroup of patients with intact lower limbs arteries, the increase in brachial artery diameter was 9.60% an average (p=0.04). Among 51 people with affection of both vascular systems the brachial artery diameter increase was 5.4%, while in comparison, in the subgroup consisting of 49 patients without combined carotid and lower limb arteries lesions, - 9.9% (p=0.003). According to the results of the correlation analysis, the relation between endothelial dysfunction and the maximum percentage of stenosis of the carotid arteries and lower limb arteries at the level of tibial segment was revealed.Conclusion. In patients with hypertension and peripheral artery disease, decrease in dilation response in endothelium-dependent vasodilation test was registered regardless of the localization of atherosclerotic lesions; endothelial dysfunction in essential hypertension was associated with the highest percentage of stenosis of the carotid arteries and lower limb arteries at the level of tibial segment.

On the etiology of cardiovascular diseases: A new framework for understanding literature results

The interpretative framework presented here provides a rationale for many well-known features of cardiovascular diseases. Prolonged acidemia with high blood levels of free fatty acids is proposed to shape the basic context for formation of fatty acid micelles and vesicles with an acidic core that fuse with the endothelia, disrupt vital cell processes, and initiate atherosclerotic plaque formation. It offers an explanation for the distributed localization of atherosclerotic lesions, and how mild cases of occurrence of fatty acids vesicles formed within the heart and the arteries close to the heart may cause such lesions. It provides a rationale for how acute events, namely heart attacks and strokes, may arise from stormy development of fatty acid vesicles within the heart. Additionally, a process is proposed for clot development from the existing fatty acid vesicles.

FSI SIMULATION OF A HEALTHY CORONARY BIFURCATION FOR STUDYING THE MECHANICAL STIMULI OF ENDOTHELIAL CELLS UNDER DIFFERENT PHYSIOLOGICAL CONDITIONS

Atherosclerosis is a world-spread and well-known disease. This disease strongly relates to the endothelial cells (ECs) function. Normally, the endothelial cells align in the flow direction in the atheroprotected sites; however, in the case of atheroprone sites these cells orient randomly. The mechanical stimuli such as wall shear stress and strains could determine the morphology and function of the endothelial cells. In the present study, we numerically simulated the left main coronary artery (LCA) and its branches to left anterior descending (LAD) and left circumflex coronary (LCX) artery using fluid–structure interaction (FSI) modeling. The results were presented as longitudinal and circumferential strains of ECs as well as wall shear stress. Wide ranges of heart rate, cardiac motion, systolic and diastolic pressures were considered and their effects on mechanical stimuli were described in detail. The results showed that these factors could greatly influence the risk of atherosclerosis and the location of atherosclerotic lesions.

Factor Analysis of Predicting Cardiovascular Death in the Remote Period after Myocardial Revascularization

The aim of the present study was to analyze the impact of traditional and renal risk factors (RFs) on the probability of cardiovascular death in CHD patients in the remote period after myocardial revascularization (MR). Materials and Methods: The present study included 90 CHD patients (80 men and 10 women; mean age 56.1±0.9 years) with indications for MR. The prevalence of major cardiovascular RFs (old age, gender, duration of CHD, arterial hypertension, diabetes mellitus, another localization of atherosclerotic lesions, and the presence and duration of smoking) and the main echocardiographic parameters and the parameters of renal function (MAU and GFR) were assessed. Fatal cardiovascular outcomes were the only endpoint of the study. Results: Cardiovascular death (CVD) occurred in 10/12.3% patients. The studied RFs, such as the patient’s age, duration of smoking, and presence of angina with low tolerance to physical stress, had a significant impact on the probability of death in CHD patients. Risk of CVD (rCVD) over a long-term period increases by 18.1% in patients with elevated levels of total cholesterol, by 16.2% in patients with stable angina pectoris class III, by 50.5% in patients with atherosclerotic lesions of lower limb and cerebral arteries, and by 69.3% in patients suffering from overweight. Left atrial size, LVPWT, and LVMI were also significant predictors of adverse cardiovascular prognosis. The increase in the number of coronary arteries with clinically significant stenosis, including subtotal narrowing of the vessel lumen, increases rCVD in the long-term period. The important role of a highly reliable level of glucose in the urine for the risk score was found. The presence of CKD stage 3 and the impaired GFR also significantly increased rCVD.

Insights on atherosclerosis by non-invasive assessment of wall stress and arterial morphology along the length of human coronary plaques.

Wall stress (WS) is associated with high arterial pressure and affects the localization of atherosclerotic lesions. We sought to non-invasively investigate the distribution of WS along the length of human coronary arteries and investigate its potential effect on atherosclerosis in association with vascular stiffness, local arterial curvature and plaque volume. We reconstructed three-dimensionally 28 coronary arteries from 22 subjects who had undergone coronary computed tomography angiography. Coronary arteries were divided in 2 mm-long segments. WS, vascular stiffness, plaque volume and curvature were calculated in each segment using computational fluid dynamics and morphology measurements. Plaque segments exhibited lower WS compared to their adjacent normal segments. Within plaques, WS was lower in the mid plaque portion compared to the upstream portion. Plaque volume was higher in the mid plaque portion compared to upstream and downstream portions. Low WS was associated with high curvature and both low WS and high curvature were associated with increased plaque volume. The current study demonstrates that WS and plaque volume are not uniform in the longitudinal axis of human coronary plaque. Calculation of WS could serve as a surrogate for the localization of plaque development and the identification of plaques at a more advanced stage of progression.

Correlation of Hemodynamic Parameters to Endothelial Cell Proliferation in an End to Side Anastomosis

A strong correlation between the localization of atherosclerotic lesions with abnormal wall shear stress (WSS) has long been recognized at the distal anastomosis of a peripheral bypass where disturbed flow occurs. Identification of a WSS variable that significantly contributes to disease formation at this site has been elusive to date, as endothelial cell (EC) response to the abnormal hemodynamics at this anastomotic junction has yet to be quantitatively characterized. In vitro experiments were performed exposing human aortic ECs to pulsatile flow variables appropriate to a distal bypass graft junction using a novel in vitro device. Computational fluid dynamics was employed to detail the hemodynamic variables of this flow chamber. These variables were then correlated to EC proliferation which was used as an indicator of intimal hyperplasia (IH) development. Under pulsatile flow, maximum absolute temporal WSS gradient was found to be the parameter that most significantly correlated to EC proliferation (p = 0.0001, r = 0.8947). This metric can be utilized as an indicator to detect arterial segments prone to the initiation and localization of IH, it may also be used to help optimize the surgical construction of coronary artery bypass, peripheral bypass and arteriovenous anastomotic junctions to improve patient outcomes.

The impact of left main coronary artery morphology on the distribution of atherosclerotic lesions in its branches

Atherosclerotic occlusion of a coronary vessel is the commonest cause of ischaemic heart disease. The distribution of atherosclerotic lesions is not random,with stenoses preferentially situated at branch ostia, bifurcation points, and the proximal segments of daughter vessels. The aim of this study was to determine the effect of the intrinsic anatomical properties of the left main coronary artery(LMCA) on the distribution of atherosclerotic lesions in its branches. A retrospective review of 170 consecutive coronary angiograms obtained from the cardiac catheterisation laboratories of private hospitals in the eThekwini Municipality area of KwaZulu-Natal, South Africa was performed. The LMCA was absent in 19/170 (11.2%). The remaining angiograms(n = 151) were divided into two groups: normal 63/151 (41.7%) and those with coronary artery disease (CAD) 88/151 (58.3%). The CAD group was sub-divided into proximal 42/88 (47.7%), mixed (proximal and distal) 26/88 (29.6%) and distal20/88 (22.7%) sub-groups based on the location of atherosclerotic lesions in the branches of the LMCA. The mean length, diameter and angle of division of the LMCA were as follows: Total angiograms: 10.4 mm, 3.8 mm and 86.2o; normal group:10.5 mm, 3.9 mm and 85.7o, CAD group: 10.2 mm, 3.7 mm and 86.3o; proximal sub-group: 10.9 mm, 3.7 mm and 91.6o, mixed sub-group - 9.8 mm, 3.7 mm and 85o and distal sub-group - 9.1 mm, 3.8 mm and 79.4o, respectively. The vessels with proximally located lesions were recorded to have longer lengths and wider angles of division than vessels with distal lesions. Coronary angiographic delineation of the LMCA anatomy may be predictive of a coronary arterial arrangement that may favour the progression of proximally located lesions.

Does low and oscillatory wall shear stress correlate spatially with early atherosclerosis? A systematic review.

Low and oscillatory wall shear stress is widely assumed to play a key role in the initiation and development of atherosclerosis. Indeed, some studies have relied on the low shear theory when developing diagnostic and treatment strategies for cardiovascular disease. We wished to ascertain if this consensus is justified by published data. We performed a systematic review of papers that compare the localization of atherosclerotic lesions with the distribution of haemodynamic indicators calculated using computational fluid dynamics. The review showed that although many articles claim their results conform to the theory, it has been interpreted in different ways: a range of metrics has been used to characterize the distribution of disease, and they have been compared with a range of haemodynamic factors. Several studies, including all of those making systematic point-by-point comparisons of shear and disease, failed to find the expected relation. The various pre- and post-processing techniques used by different groups have reduced the range of shears over which correlations were sought, and in some cases are mutually incompatible. Finally, only a subset of the known patterns of disease has been investigated. The evidence for the low/oscillatory shear theory is less robust than commonly assumed. Longitudinal studies starting from the healthy state, or the collection of average flow metrics derived from large numbers of healthy vessels, both in conjunction with point-by-point comparisons using appropriate statistical techniques, will be necessary to improve our understanding of the relation between blood flow and atherogenesis.

Structural and biochemical characteristics of arterial stiffness in patients with atherosclerosis and in healthy subjects

Arterial stiffness is an independent predictor of vascular morbidity and mortality in patients with atherosclerosis. Angiographic score (ASc) reflects severity of atherosclerosis in patients with peripheral arterial disease (PAD). Osteopontin (OPN) and oxidized low-density lipoprotein (oxLDL) are involved in the pathogenesis of atherosclerosis. The aim of the present study was to evaluate the association between arterial stiffness, ASc, serum OPN and oxLDL in patients with symptomatic PAD, and in clinically healthy subjects. We studied 79 men with symptomatic PAD (mean age 64±7 years) and 84 healthy men (mean age 63±8 years). Calculation of the ASc was based on severity and location of atherosclerotic lesions in the arteries of the lower extremities. Aortic pulse wave velocity (aPWV) was evaluated by applanation tonometry using the Sphygmocor device. Serum OPN and oxLDL levels were determined by enzyme-linked immunosorbent assay. The aPWV (10±2.4 vs. 8.4±1.7 (m s(-1)); P<0.001), OPN (75 (62.3-85.8) vs. 54.8 (47.7-67.9) (ng ml(-1)); P<0.001) and oxLDL (67 (52.5-93.5) vs. 47.5 (37-65.5); P<0.001) were different for the patients and for the controls. In multiple regression models, aPWV was independently determined by ASc, log-OPN, log-oxLDL and estimated glomerular filtration rate in the patients (R2=0.44; P<0.001) and by log-OPN, log-oxLDL, age and heart rate in the controls (R2=0.38; P<0.001). The independent relationship of a PWV with serum levels of OPN and oxLDL in the patients with PAD and in the controls indicates that OPN and oxLDL might influence arterial stiffening in patients with atherosclerosis and in clinically healthy subjects.

Abstract 3579: Prevalence And Distribution Of Asymptomatic Cervicocephalic Atherosclerosis In A Caucasian Population: Risk Factors And Biomarkers

Objective: To study clinical and biological factors associated with the different cervicocephalic location of atherosclerosis in Caucasian stroke-free individuals. Methods: Carotid and intracranial atherosclerosis were assessed in the same lab by ECO-Doppler in a random sample population of 933 Caucasian subjects older than 50, with a moderate-high vascular risk and without history of stroke (64% males, mean age 66 years). Hypertension, dyslipemia, diabetes and smoking habit were defined based on clinical history and/or current medications. The following inflammatory and endothelial dysfunction biomarkers were determined at baseline and considered as continuous variables for the analyses: C-reactive protein (CRP), plasminogen activator inhibitor (PAI-1), resistin and asymmetric dimethylarginine (ADMA). Results: Subjects were classified according to the cervicocephalic location of atherosclerotic lesions: 449 (48.1%) had no lesions (reference group), 404 (43.3%) had isolated carotid extracranial lesions (EC), 57 (6.1%) had isolated intracranial lesions (IC) and 23 (2.5%) had combined extra-intracranial lesions (C). After multinomial regression analyses, factors independently associated with each location of atherosclerosis compared to the reference group were: with EC, age (OR 1.06[1.04-1.09]p&lt;0.001), male sex (OR 1.8[1.3-2.5]p=0.001), hypertension (OR 1.5[1.1-2]p=0.001), smoking (OR 1.7[1.2-2.4]p=0.004) and ADMA levels (1.7[1.05-2.9]p=0.03); with IC, age (OR 1.07[1.03-1.12]p&lt;0.001), diabetes (OR 3.5[1.7-7.3]p=0.001) and ADMA levels (OR 3.2[1.3-8.1]p=0.01); with C, age (OR 1.2[1.05-1.2]p&lt;0.001), male sex (OR 4.8[1.4-15.9]p&lt;0.001), diabetes (OR 6.4[2.1-19.4]p=0.001), hypertension (OR 7.1[1.5-32.9]p=0.01) and resistin levels (OR 1.1[1.008-1.26]p=0.03). Conclusions: Our findings show distinct clinical and biological signatures of the cervico-cephalic location of subclinical atherosclerosis.

Wprowadzenie do numerycznej mechaniki płynu na podstawie komputerowej symulacji przepływu w lewej tętnicy wieńcowej

ENWEndNote BIBJabRef, Mendeley RISPapers, Reference Manager, RefWorks, Zotero AMA Wasilewski J, Mirota K, Peryt-Stawiarska S, Nowakowski A, Poloński L, Zembala M. An introduction to computational fluid dynamics based on numerical simulation of pulsatile flow in the left coronary artery. Kardiochirurgia i Torakochirurgia Polska/Polish Journal of Thoracic and Cardiovascular Surgery. 2012;9(3):366-374. doi:10.5114/kitp.2012.30851. APA Wasilewski, J., Mirota, K., Peryt-Stawiarska, S., Nowakowski, A., Poloński, L., & Zembala, M. (2012). An introduction to computational fluid dynamics based on numerical simulation of pulsatile flow in the left coronary artery. Kardiochirurgia i Torakochirurgia Polska/Polish Journal of Thoracic and Cardiovascular Surgery, 9(3), 366-374. https://doi.org/10.5114/kitp.2012.30851 Chicago Wasilewski, Jarosław, Kryspin Mirota, Sylwia Peryt-Stawiarska, Andrzej Nowakowski, Lech Poloński, and Marian Zembala. 2012. "An introduction to computational fluid dynamics based on numerical simulation of pulsatile flow in the left coronary artery". Kardiochirurgia i Torakochirurgia Polska/Polish Journal of Thoracic and Cardiovascular Surgery 9 (3): 366-374. doi:10.5114/kitp.2012.30851. Harvard Wasilewski, J., Mirota, K., Peryt-Stawiarska, S., Nowakowski, A., Poloński, L., and Zembala, M. (2012). An introduction to computational fluid dynamics based on numerical simulation of pulsatile flow in the left coronary artery. Kardiochirurgia i Torakochirurgia Polska/Polish Journal of Thoracic and Cardiovascular Surgery, 9(3), pp.366-374. https://doi.org/10.5114/kitp.2012.30851 MLA Wasilewski, Jarosław et al. "An introduction to computational fluid dynamics based on numerical simulation of pulsatile flow in the left coronary artery." Kardiochirurgia i Torakochirurgia Polska/Polish Journal of Thoracic and Cardiovascular Surgery, vol. 9, no. 3, 2012, pp. 366-374. doi:10.5114/kitp.2012.30851. Vancouver Wasilewski J, Mirota K, Peryt-Stawiarska S, Nowakowski A, Poloński L, Zembala M. An introduction to computational fluid dynamics based on numerical simulation of pulsatile flow in the left coronary artery. Kardiochirurgia i Torakochirurgia Polska/Polish Journal of Thoracic and Cardiovascular Surgery. 2012;9(3):366-374. doi:10.5114/kitp.2012.30851.

Effects of Disturbed Flow on Vascular Endothelium: Pathophysiological Basis and Clinical Perspectives

Vascular endothelial cells (ECs) are exposed to hemodynamic forces, which modulate EC functions and vascular biology/pathobiology in health and disease. The flow patterns and hemodynamic forces are not uniform in the vascular system. In straight parts of the arterial tree, blood flow is generally laminar and wall shear stress is high and directed; in branches and curvatures, blood flow is disturbed with nonuniform and irregular distribution of low wall shear stress. Sustained laminar flow with high shear stress upregulates expressions of EC genes and proteins that are protective against atherosclerosis, whereas disturbed flow with associated reciprocating, low shear stress generally upregulates the EC genes and proteins that promote atherogenesis. These findings have led to the concept that the disturbed flow pattern in branch points and curvatures causes the preferential localization of atherosclerotic lesions. Disturbed flow also results in postsurgical neointimal hyperplasia and contributes to pathophysiology of clinical conditions such as in-stent restenosis, vein bypass graft failure, and transplant vasculopathy, as well as aortic valve calcification. In the venous system, disturbed flow resulting from reflux, outflow obstruction, and/or stasis leads to venous inflammation and thrombosis, and hence the development of chronic venous diseases. Understanding of the effects of disturbed flow on ECs can provide mechanistic insights into the role of complex flow patterns in pathogenesis of vascular diseases and can help to elucidate the phenotypic and functional differences between quiescent (nonatherogenic/nonthrombogenic) and activated (atherogenic/thrombogenic) ECs. This review summarizes the current knowledge on the role of disturbed flow in EC physiology and pathophysiology, as well as its clinical implications. Such information can contribute to our understanding of the etiology of lesion development in vascular niches with disturbed flow and help to generate new approaches for therapeutic interventions.

Relationship between individual cardiovascular risk factors and localization of coronary atherosclerotic lesions

Objective The localization of coronary atherosclerotic lesions in patients with coronary artery disease is important. We investigated the relationship between individual cardiovascular risk factors and lesion localization in the coronary arteries. Methods We studied 200 consecutive patients with suspected or known coronary artery disease who were referred for coronary angiography because of chest pain. We assessed the following cardiovascular risk factors: male gender, hypercholesterolemia, smoking, arterial hypertension, positive family history, and diabetes. We evaluated atherosclerotic lesions creating a stenosis ≥ 50% in the 3 coronary arteries and lesions creating a stenosis ≥ 30% in the left main stem. Results Of the 200 study patients, 155 (78%) showed at least 1 coronary artery lesion with a luminal stenosis ≥ 50%. With an increasing number of risk factors, there was a significant progressive increase of diseased arteries ( P < .001). There was a differential association between individual risk factors and lesions in the 3 coronary arteries. Male gender, hypercholesterolemia, and diabetes were predictors of lesions in the left anterior descending artery (odds ratios 2.365, 2.510, and 1.998, respectively). Predictors of left circumflex artery lesions were male gender, smoking, and diabetes (odds ratios 2.581, 1.913, and 2.280, respectively), whereas the only independent predictor of right coronary artery lesions was male gender (odds ratio 2.995). Diabetes was also significantly associated with lesions in the diagonal branches of the left anterior descending artery and the marginal branches of the left circumflex artery. Conclusion Individual cardiovascular risk factors are associated with the localization of atherosclerotic lesions in the coronary circulation.

Increased oxidative stress in atherosclerosis-predisposed regions of the mouse aorta

Aims The localization of atherosclerotic lesions to predictable regions in mammalian arteries has been recognized for over a century. We sought to investigate the association between oxidative stress and regional susceptibility of the mouse aorta to atherosclerosis. Main methods En face confocal microscopy was employed to assess oxidative stress in the aortic intima of atherosclerosis-susceptible and protected regions of wild-type C57BL/6 mouse. Expression of reactive oxygen species and antioxidant producing genes were compared in endothelial cells from the susceptible and protected regions. Key findings In vivo administration of redox-sensitive fluorescent dyes revealed an increase in the production of reactive oxygen species (ROS) in the atherosclerosis-susceptible regions relative to the protected regions. In contrast, Hoechst a redox-insensitive dye distributed evenly in the susceptible and protected regions. Accumulation of superoxide in the susceptible regions of the aorta was significantly blocked by the administration of Diphenyleneiodonium, a flavoprotein inhibitor. mRNA levels of superoxide-producing and scavenging enzymes were significantly increased in the regions predisposed to atherosclerosis. The regional difference in oxidative stress was at a lesser magnitude in BALB/c than the atherosclerosis-susceptible mouse (C57BL/6). Significance Our study for the first time demonstrated an augmented oxidative stress in atherosclerosis-susceptible regions of the normal mouse aorta.