Artery Atherosclerosis Research Articles

Mechanoregulation and function of calponin and transgelin.

It is well known that chemical energy can be converted to mechanical force in biological systems by motor proteins such as myosin ATPase. It is also broadly observed that constant/static mechanical signals potently induce cellular responses. However, the mechanisms that cells sense and convert the mechanical force into biochemical signals are not well understood. Calponin and transgelin are a family of homologous proteins that participate in the regulation of actin-activated myosin motor activity. An isoform of calponin, calponin 2, has been shown to regulate cytoskeleton-based cell motility functions under mechanical signaling. The expression of the calponin 2 gene and the turnover of calponin 2 protein are both under mechanoregulation. The regulation and function of calponin 2 has physiological and pathological significance, as shown in platelet adhesion, inflammatory arthritis, arterial atherosclerosis, calcific aortic valve disease, post-surgical fibrotic peritoneal adhesion, chronic proteinuria, ovarian insufficiency, and tumor metastasis. The levels of calponin 2 vary in different cell types, reflecting adaptations to specific tissue environments and functional states. The present review focuses on the mechanoregulation of calponin and transgelin family proteins to explore how cells sense steady tension and convert the force signal to biochemical activities. Our objective is to present a current knowledge basis for further investigations to establish the function and mechanisms of calponin and transgelin in cellular mechanoregulation.

Photoacoustic imaging of peripheral vessels in extremities by large-scale synthetic matrix array.

Various peripheral vascular diseases (PVD) in extremities, such as arterial atherosclerosis or venous occlusion in arm or legs, are a serious global health threat. Noninvasive vascular imaging is of great value for both diagnosis and assessment of PVD. By scanning a one-dimensional non-focusing linear array, an equivalent large two-dimensional (2D) matrix array with hundreds of thousands or more ultrasound elements is formed, thereby achieving a wide signal reception angle as well as large imaging area for three-dimensional (3D) imaging of peripheral extremities. To provide a feasible bedside and noninvasive imaging method for vascular imaging in extremities. Our system can achieve high-quality photoacoustic (PA) peripheral vessel imaging. The 3D subcutaneous vascular imaging results of the palms and arms of healthy volunteers demonstrate the superior performance of the system. This work proposes a clinically oriented PA 3D subcutaneous vascular imaging system for human extremities. The system employs a synthetic matrix array via scanning a one-dimensional non-focusing linear probe, providing noninvasive, high-resolution, and high-contrast images of human extremities. It has potential application value in the diagnosis and monitoring of vascular diseases.

Cheese consumption on atherosclerosis, atherosclerotic cardiovascular diseases and its complications: A two-sample Mendelian randomization study

Background and aimEvidence from prospective cohort studies has revealed an inverse association between cheese consumption and the development of atherosclerosis (AS), atherosclerotic cardiovascular diseases (ASCVD), and their complications. However, it remains unclear whether this observed association is influenced by potential confounding factors that may arise during the long-term development process of AS, ASCVD, and its complications. Therefore, to further clarify the causal relationship between cheese consumption and AS, ASCVD, and its complications, we conducted a two-sample Mendelian randomization (MR) analysis to explore the causal association between cheese intake and the aforementioned health outcomes. Methods and resultsWe employed a two-sample MR analysis based on publicly available genome-wide association studies (GWAS) to infer the causal relationship, with no overlap between their participating populations. The effect estimates were calculated using the random-effects inverse-variance-weighted method. Sensitivity analyses were conducted using Cochran's Q statistic, funnel plot, leave-one-out analysis, and MR-Egger intercept tests. The genetically predicted cheese intake was found to be associated with lower risks of coronary AS (odds ratio [OR] = 0.72, 95 % confidence interval [CI] 0.59–0.88, P = 0.001), peripheral vascular AS (OR = 0.56, 95 % CI 0.37–0.84, P = 0.006), other vascular AS (OR = 0.66, 95 % CI 0.44–0.99, P = 0.043), coronary artery disease (OR = 0.64, 95 % CI 0.56–0.74, P = 1.57e-09), angina pectoris (OR = 0.70, 95 % CI 0.58–0.84, P = 4.92e-05), myocardial infarction (OR = 0.63, 95 % CI 0.52–0.77, P = 3.56e-06), heart failure (OR = 0.62, 0.49–0.79, P = 1.20e-04), total ischemic stroke (OR = 0.76, 95 % CI 0.63–0.91, P = 0.003), peripheral artery disease (OR = 0.64, 95 % CI 0.43–0.95, P = 0.028), and cognitive impairment (OR = 0.65, 95 % CI 0.56–0.74, P = 3.40e-10). However, no associations were observed for cerebrovascular AS, arrhythmia, cardiac death, ischemic stroke (large artery AS), ischemic stroke (small vessel), ischemic stroke (cardioembolic), and transient ischemic attack. ConclusionThis two-sample MR analysis reveals a causally inverse association between cheese intake and multi-vascular AS (including coronary AS, peripheral vascular AS, and other vascular AS), as well as multiple types of ASCVD and its complications (such as coronary artery disease, angina pectoris, myocardial infarction, heart failure, total ischemic stroke, and peripheral artery disease). The findings from this study may lay a stronger theoretical foundation and present new opportunities for the dietary management of future atherosclerotic cardiovascular diseases.

The observation of below-the-knee artery by optical frequency domain image and angioscopy: a case series

Abstract Background Endovascular treatment (EVT) is a well-established treatment for patients with chronic limb-threatening ischaemia, and below-the-knee (BTK) artery is its main target, although the re-intervention rate is still high. Understanding of the characteristics of BTK artery atherosclerosis would be required to overcome this issue. In this case series, we elucidated the characteristics of non-stenotic BTK artery atherosclerosis in the patients who received EVT of the superficial femoral artery (SFA) using optical frequency domain imaging (OFDI) and angioscopy. Case summary We presented five patients who underwent EVT of SFA and subsequent observation of ipsilateral BTK artery using OFDI and angioscopy. Patients one and two had advanced atherosclerosis; however, patients three, four, and five had only mild atherosclerosis. Discussion All patients had multiple risk factors for atherosclerosis and stenosis/occlusion of the SFA and ipsilateral BTK arteries. Furthermore, some patients had several other atherosclerotic vascular diseases suggesting the presence of advanced systemic atherosclerosis. On the other hand, some patients with multiple BTK artery stenosis/occlusion did not have advanced atherosclerosis in the examined BTK artery. The absence of significant atherosclerosis in a BTK artery in patients with multiple stenoses or occlusion in other ipsilateral BTK arteries may suggest some mechanism of vessel occlusion other than atherosclerosis. Further investigations are needed to clarify the mechanism.

Peripheral Arterial Disease and the Pharmacist’s Role in Management

Purpose. Atherosclerosis of arteries in the legs leads to peripheral arterial disease (PAD), increasing the risk of future cardiovascular events. Worldwide prevalence estimates indicate >200 million people have PAD, but this is likely underestimated given the variability in symptoms and lack of awareness by patients and clinicians. Antiplatelet therapy is recommended to reduce cardiovascular risk, but anticoagulation therapy may also be beneficial. This narrative review examined scientific literature for the burden and medical management of PAD, including use of anticoagulants in this population, and provides perspectives on the role of pharmacists to improve outcomes of PAD. Summary. A variety of antiplatelet therapies has been studied in patients with PAD, and treatment is recommended for those with symptomatic disease. The use of dual antiplatelet therapy is limited to patients with symptomatic PAD after revascularization. Anticoagulation with warfarin in combination with antiplatelet therapy did not improve efficacy over antiplatelet therapy alone and increased bleeding. In contrast, the direct factor Xa inhibitor rivaroxaban, when used in combination with low-dose aspirin, has been shown to significantly reduce the risk of cardiovascular death, myocardial infarction (MI), or stroke by 28% in patients with PAD compared with aspirin alone. Similarly, in patients with PAD who have undergone revascularization, rivaroxaban plus aspirin reduced the risk of acute limb ischemia, major amputation, MI, stroke, or cardiovascular death by 15% versus aspirin alone. Major bleeding was significantly increased with rivaroxaban plus aspirin, but with no differences in fatal bleeding, nonfatal intracranial hemorrhage, or symptomatic bleeding into a critical organ between groups. Pharmacist-led interventions for patients with PAD include identifying at-risk patients through medication reviews and clinical assessments, education and monitoring use of prescription and over-the-counter medications, and appropriate counseling on lifestyle modifications. Conclusion. Rivaroxaban plus aspirin reduces the risk of major cardiovascular events, including major adverse limb events and amputation, in patients with PAD. Pharmacists can play an integral role in identifying, screening, and managing patients with PAD to achieve favorable outcomes.

The microvascular bed of the skin of lower limbs in patients with intermittent lameness and coronary heart disease as a possible model of their myocardial microcirculation

Purpose: to assess possibility to extrapolate findings of skin microvascular bed examination in lower extremities with laser Doppler flowmetry in patients with obliterating atherosclerosis as a model of their myocardial microcirculation in coronary heart disease.Material and methods. Males with angiographically confirmed coronary heart disease (n = 70) and obliterating atherosclerosis in lower limbarteries (n = 74) were taken in the study. Microcirculation of the skin in the left forearm in the Zakharyin – Head zone in patients with coronaryheart disease and skin microcirculation in the foot of affected limb in patients with obliterating atherosclerosis of arteries of lower extremities were examined with laser Doppler flowmetry. The basal blood flow, amplitude-frequency spectrum of its oscillations, myogenic, neurogenic vascular tone and occlusion parameters were assessed as well. Comparison groups included 50 practically healthy males for the patients with coronary heart disease and 20 males – for the patients with obliterating atherosclerosis of arteries of lower extremities. Patients were examinedat the initial stage and in 2–3 weeks after endovascular restoration of blood flow in the myocardium and lower limbs.Results and discussion. At the initial research stage, the microcirculation picture in patients with coronary heart disease and obliterating ath-erosclerosis in lower extremities differed from that of healthy individuals by shifts covering all links of the microvascular bed and characterizedby constriction of the precapillary segment, a statistically significant decrease in median values of capillary blood flow by 17.5 and 43.1 %,microvascular blood flow reserve – by 11.2 and 31.0 %, as well as by the increase in arteriolovenular blood bypass – by 10.3 and 70.8 %,respectively. After the restoration of blood flow in lower extremities in patients with obliterating atherosclerosis, muscular pain disappeared,and the ankle-shoulder index got normalized. At the same time, one could observe a statistically significant increase in the capillary blood flow(+13.6 %), the increase of reserve potential in microvascular bed (+20.6 %) with the simultaneous decrease of vascular tone in the precapillarysegment (–15.1 %) and of the blood bypass index (–25.0 %). Better clinical picture after coronary angioplasty in patients with coronary heart disease was accompanied with a similar and unidirectional tendency to positive changes in the microvascular bed.Conclusion. As far as etiopathogenetic mechanisms and clinical manifestations of coronary heart disease and obliterating atherosclerosis in arteries of lower extremities have much in common and microcirculatory shifts in forearm and foot skin in these patients before and after angioplasty are unidirectional, all these allow to suggest that one can see similar changes in the myocardium microcirculatory system in patients with coronary heart disease. Thus, it opens possibilities to have a targeted medicamentous impact at the microvascular level.

Estimation of Mouse Carotid Arterial Wall Shear Stress Using High-Frequency Ultrasound Imaging.

Wall shear stress (WSS) is a crucial hemodynamic factor that promotes atherosclerosis (plaque) development in arteries; although the relationship between WSS and arterial atherosclerosis has been explored in many animal studies, it is not fully understood. No suitable tool, however, exists for rapidly estimating dynamic WSS in small-animal studies. This study proposes a 40-MHz high-frequency ultrasound (HFUS) imaging system for dynamic WSS estimation based on mouse carotid artery blood flow velocity gradient measurements by vector Doppler imaging (VDI). Aliasing reduces the accuracy of Doppler measurements, which can be prevented by increasing the imaging frame rate. Conventionally, imaging is performed at two tilted angles by alternating between the angles; in the proposed method, the frame rate was doubled by imaging at each tilted angle sequentially and by then temporally aligning the sequences based on pulsatile flow characteristics. Velocity estimation using this method had low errors for both a steady-flow straight-tube and pulsatile flow 60%-stenosis phantom. The method was tested for wild-type (WT) C57BL/6 mice at 16 weeks old and apolipoprotein E knockout (ApoE KO) mice at 16 and 24 weeks old; differences in time-averaged and oscillatory WSS were observed, and histology confirmed that the 24-week ApoE KO mice with the highest oscillatory WSS had the greatest plaque formation. The proposed HFUS WSS imaging method can predict the location and extent of plaque development; thus, this method is useful for small-animal studies investigating the WSS effect on atherosclerotic plaque development.

Extensive diet-induced atherosclerosis in scavenger receptor class B type 1-deficient mice is associated with substantial leukocytosis and elevated vascular cell adhesion molecule-1 expression in coronary artery endothelium.

High levels of low density lipoprotein (LDL) cholesterol and low levels of high density lipoprotein (HDL) cholesterol are risk factors for cardiovascular disease. Mice that lack genes involved in the clearance of LDL from the bloodstream, such as the LDL receptor and apolipoprotein E, are widely used models of experimental atherosclerosis. Conversely, mice that lack the HDL receptor, scavenger receptor class B type I, and therefore have disrupted HDL functionality, also develop diet-inducible atherosclerosis but are a seldom-used disease model. In this study, we compared atherosclerosis and associated phenotypes in scavenger receptor class B type I knockout mice with those of wild type, LDL receptor knockout, and apolipoprotein E knockout mice after 20weeks of being fed an atherogenic diet containing sodium cholate. We found that while scavenger receptor class B type I knockout mice had substantially lower plasma cholesterol than LDL receptor and apolipoprotein E knockout mice, they developed atherosclerotic plaques with similar sizes and compositions in their aortic sinuses, and more extensive atherosclerosis in their descending aortas and coronary arteries. This was associated with elevated tumor necrosis factor alpha levels in scavenger receptor class B type I knockout mice compared to wild type and LDL receptor knockout mice, and lymphocytosis, monocytosis, and elevated vascular cell adhesion molecule expression in coronary artery endothelial cells compared to the other mice examined. We conclude that extensive atherosclerosis in arteries that are not generally susceptible to atherosclerosis in scavenger receptor class B type I knockout mice is driven by factors in addition to hypercholesterolemia, including inflammation, dysregulation of the immune system and increased sensitivity of endothelial cells in arteries that are normally resistant to atherosclerosis. Scavenger receptor class B type I knockout mice fed a cholate containing atherogenic diet may prove to be a useful model to study mechanisms of atherosclerosis and evaluate treatments that rely on intact LDL clearance pathways.

PS-C04-6: ASSOCIATION BETWEEN SERUM URATE LEVEL AND CAROTID ATHEROSCLEROSIS: AN INSIGHT FROM A POST-HOC ANALYSIS OF THE RANDOMIZED CLINICAL TRIAL (PRIZE)

Objectives: Elevated serum urate (SU) levels are associated with arterial atherosclerosis and subsequent cardiovascular events. However, an optimal therapeutic target SU level for delaying atherosclerotic progression in patients with hyperuricemia remains uncertain. The aim of this analysis was to assess an association between changes in SU level and carotid intima-media thickness (IMT) to examine whether an optimal SU concentration exists to delay atherosclerotic progression. Design and method: This was a post-hoc analysis of the PRIZE (program of vascular evaluation under uric acid control by xanthine oxidase inhibitor, febuxostat: multicenter, randomized controlled) study of Japanese adults with asymptomatic hyperuricemia (UMIN000041322). Among the full analysis set population treated with febuxostat (n = 239), subjects who had both data on SU level and mean common carotid artery (CCA)-IMT at baseline and 24 months were included in the present analysis. The primary endpoint of this analysis was an association between changes in SU levels and mean CCA-IMT after 24 months of febuxostat treatment. Results: A total of 204 eligible subjects were included in this analysis. The mean age was 69.1 +/- 9.6 years, and one fifth were female. Most had a history of treated hypertension and/or dyslipidemia. The mean baseline SU level was 7.7 ± 1.0 mg/dL, and febuxostat treatment significantly reduced SU concentrations at 24 months (estimated mean change -3.1 mg/dL, 95% confidence interval -3.2 to -2.9). A multivariable linear regression analysis revealed that a reduction in SU level was associated with changes in mean CCA-IMT values at 24 months (Figure A). In contrast, the achieved SU concentrations were not associated with changes in mean CCA-IMT at 24 months (Figure B). Conclusion: A greater reduction in SU, but not its achieved concentrations, may be associated with delayed progression of carotid IMT in patients with asymptomatic hyperuricemia treated with febuxostat.

Sleeve gastrectomy improves lipid dysmetabolism by downregulating the USP20-HSPA2 axis in diet-induced obese mice.

Obesity is a metabolic disease accompanied by abnormalities in lipid metabolism that can cause hyperlipidemia, non-alcoholic fatty liver disease, and artery atherosclerosis. Sleeve gastrectomy (SG) is a type of bariatric surgery that can effectively treat obesity and improve lipid metabolism. However, its specific underlying mechanism remains elusive. We performed SG, and sham surgery on two groups of diet-induced obese mice. Histology and lipid analysis were used to evaluate operation effect. Immunohistochemistry, immunoblotting, real-time quantitative PCR, immunoprecipitation, immunofluorescence and mass spectrometry were used to reveal the potential mechanisms of SG. Compared to the sham group, the SG group displayed a downregulation of deubiquitinase ubiquitin-specific peptidase 20 (USP20). Moreover, USP20 could promote lipid accumulation in vitro. Co-immunoprecipitation and mass spectrometry analyses showed that heat-shock protein family A member 2 (HSPA2) potentially acts as a substrate of USP20. HSPA2 was also downregulated in the SG group and could promote lipid accumulation in vitro. Further research showed that USP20 targeted and stabilized HSPA2 via the ubiquitin-proteasome pathway. The downregulation of the USP20-HSPA2 axis in diet-induced obese mice following SG improved lipid dysmetabolism, indicating that USP20-HSPA2 axis was a noninvasive therapeutic target to be investigated in the future.

Lupus Anticoagulant and Anticardiolipin Antibody IgG are Associated with Increased Atherosclerosis at the Suprainguinal Elastic and Infrainguinal Muscular Arteries in the Abdomen and Lower Extremities

PurposeWhether antiphospholipid antibodies (aPLs) cause atherosclerosis in certain arteries with specific compositions and locations remains unknown. We investigated the relationship between aPLs and their association with locations of atherosclerosis in the arteries of the abdomen and lower extremities.MethodsOf 2273 patients, 697 who underwent computed tomography angiography of the abdomen and lower extremities and aPL evaluation were included. Atherosclerosis distribution score (ADS) was employed to quantify atherosclerosis severity. Multiple linear regression analysis was performed using the ADS of the suprainguinal elastic and infrainguinal muscular arteries as dependent variables and all aPLs, conventional risk factors of atherosclerosis, and coagulation-related factors as independent variables.ResultsIn the suprainguinal elastic and infrainguinal muscular arteries, common risk factors for higher ADS were age, smoking, hypertension, higher glycated hemoglobin, male sex, decreased protein S, and increased homocysteine. Lupus anticoagulant (LA) and increased triglyceride level in the suprainguinal elastic arteries and anticardiolipin antibody (aCL) immunoglobulin (Ig)G, longer alcohol consumption duration, and increased fibrinogen level in the infrainguinal muscular arteries were also risk factors for higher ADS.ConclusionLA and aCL IgG were associated with atherosclerosis in the suprainguinal elastic and infrainguinal muscular arteries, respectively. aPLs could predict the location of atherosclerosis.

Novel expression cassettes for increasing apolipoprotein AI transgene expression in vascular endothelial cells

Transduction of endothelial cells (EC) with a vector that expresses apolipoprotein A-I (APOAI) reduces atherosclerosis in arteries of fat-fed rabbits. However, the effects on atherosclerosis are partial and might be enhanced if APOAI expression could be increased. With a goal of developing an expression cassette that generates higher levels of APOAI mRNA in EC, we tested 4 strategies, largely in vitro: addition of 2 types of enhancers, addition of computationally identified EC-specific cis-regulatory modules (CRM), and insertion of the rabbit APOAI gene at the transcription start site (TSS) of sequences cloned from genes that are highly expressed in cultured EC. Addition of a shear stress-responsive enhancer did not increase APOAI expression. Addition of 2 copies of a Mef2c enhancer increased APOAI expression from a moderately active promoter/enhancer but decreased APOAI expression from a highly active promoter/enhancer. Of the 11 CRMs, 3 increased APOAI expression from a moderately active promoter (2–7-fold; P < 0.05); none increased expression from a highly active promoter/enhancer. Insertion of the APOAI gene into the TSS of highly expressed EC genes did not increase expression above levels obtained with a moderately active promoter/enhancer. New strategies are needed to further increase APOAI transgene expression in EC.

Prevalence and overlap of potential embolic sources in embolic stroke of undetermined source: a retrospective cohort

Introduction: Embolic strokes of an undetermined source may be caused by various potential embolic sources, which can be better managed by anticoagulant or antiplatelet therapy. Identifying these sources may have diagnostic and therapeutic implications. Our objectives were to assess the prevalence and overlap of different potential embolic sources identified in a population of patients with embolic strokes of undetermined sources, and to evaluate the stroke recurrence rate according to the type and number of potential embolic sources.&#x0D; Methods: We used data from consecutive patients with ischemic stroke admitted to the department of neurology in Fattouma Bourguiba hospital (Monastir, Tunisia), between January 2017 and December 2020. Patients who met the embolic strokes of undetermined source diagnostic criteria according to the criteria of the Cryptogenic Stroke “embolic strokes of undetermined source” International Working Group were selected. The presence of each potential embolic source was assessed, and patients were categorised according to the identified potential embolic sources. The main outcome was ischemic stroke recurrence, and it was collected prospectively during follow-up after the index stroke.&#x0D; Results: Among 330 patients admitted between 2017 and 2020, 66 (20.6%) were classified as embolic strokes of undetermined source (68.2% were men, mean age 57 ±11 years). The three most prevalent potential embolic sources were atrial cardiopathy (N = 47/66; 71.2%), arterial atherosclerosis (N = 46/66; 69.7%) and left ventricular disease (N = 26/66; 39.4%). Most patients (N = 56/66; 84.8%) had ≥2 potential embolic sources. After 6-month of follow up, ischemic stroke recurrence occurred in 18 (27.3%) patients. In survival analysis, the type and the number of potential embolic sources were not statistically associated with stroke recurrence.&#x0D; Conclusion: Most patients with embolic strokes of undetermined source had multiple potential embolic sources, which overlap considerably. The type and number of potential sources were not associated with stroke recurrence. This finding may explain the negative results of large trials of secondary prevention in the Embolic strokes of undetermined source population.

Non-linear dynamic processes and their correlation with indicators of microcirculation in patients with obliterating atherosclerosis of the lower extremities arteries according to laser doppler flowmetry

Objective: To study features of nonlinear dynamic and oscillatory processes in the skin microcirculatory flow in patients with obliterating atherosclerosis in lower extremities arteries (OALEA).Material and methods. 56 male patients with obliterating atherosclerosis in the arteries of lower extremities and 15 practically healthy individuals were taken into the study. Microcirculation in the skin on feet with the assessment of nonlinear dynamic processes and spectral wavelet analysis of blood fl ow fl uctuations was studied by laser Doppler flowmetry, device “LACK-M” (firm Lazma, Russia). Normalized amplitude parameters of blood flow fluctuations in frequency ranges of hemocirculation tonus-forming factors were analyzed: endothelial, neurogenic, myogenic. Myogenic microvascular tone and capillary blood flow indices were calculated. To study nonlinear dynamic processes, the following parameters were assessed: fractal dimension, entropy and phase portrait analysis.Results. Spastic-atonic microcirculation disorders were revealed in patients with OALEA. They were characterized with metarteriole constriction and with restriction of capillary blood flow, with an increased myogenic tone and dilated arterioles. Statistically significant shifts in parameters of nonlinear dynamics in this case- in particular, decrease in entropy (–10.6 %) and in dimensions of phase portrait (–9.3%) under energy deficit in oscillatory microcirculation processes (–20.8 %) – can be interpreted as a decrease in complexity of laser Doppler flowmetric signal and better ordering in regulatory mechanisms of the peripheral blood flow.Conclusion. In patients with obliterating atherosclerosis in the arteries of lower extremities, the obtained results indicate significant functional microcirculation disorders of the spastic-atonic nature leading to the restriction of nutritive blood flow and accompanied by the lack of energy in oscillatory processes. These results have also shown the decrease in the system chaos severity which indicates limitation of connections of microcirculation control factors, simplification of the mechanisms of functioning of the microvascular bed and, as a consequence, decrease in the compensatory adaptive potential.

Determinants of left ventricular diastolic dysfunction in hemodialysis patients

Introduction: Chronic kidney disease (CKD) induces changes in the myocardium known to influence morbidity and mortality, most severe in patients with end stage renal disease. Objectives: The working hypothesis was that in patients on chronic hemodialysis the prevalence of left ventricular diastolic dysfunction is correlated with the inflammatory, oxidative, metabolic, nutritional, and atherosclerotic status. Patients and Methods: An observational study was performed on 51 patients (age 59.76 ± 13.24 years) on hemodialysis treatment. Transthoracic cardiac ultrasound was conducted to evaluate LVDD. The burden of cardiac and arterial atherosclerosis was evaluated by cardiac ultrasound (aortic and mitral valve calcifications), vascular ultrasound (carotid and femoral atheroma plaques, common carotid intima-media thickness), and by abdominal radiography (aortic calcification score). Demographic and anthropometric parameters were determined. Blood samples were used to determine laboratory parameters reflecting the inflammatory, oxidative, and metabolic/nutrition status. Results: LVDD is positively correlated with the serum level of C-reactive protein (CRP) (P=0.04), the total antioxidant capacity of the serum (P=0.04), the presence (P=0.022) and number (P=0.04) of femoral plaques, the aortic calcification score (P=0.02), aortic valve stenosis (P=0.037), aortic annulus calcifications (P=0.02) and mitral valve calcifications (P=0.041). After the removal of the main confounder, degenerative aortic stenosis, only the associations with serum total antioxidant capacity (P=0.04) and aortic calcification score (P= 0.02) maintain their statistical significance. Conclusion: LVDD is positively correlated with inflammation and oxidative stress markers and with the severity of aortic calcification.

Vascular Malperfusion – As a Morphological Pattern of Preeclampsia

Introduction. The system « mother-placenta-fetus » is in a complex functional balance, and dysfunction of any of the components can compromise others. The placenta plays an important role in the development of preeclampsia, since preeclampsia can occur in the absence of a fetus, but in the presence of a trophoblast. In this regard, the study of morphological placental patterns in preeclampsia can give an idea of preeclampsia as a pathology in general, as well as its relationship with hypoxic damage to the fetus.&#x0D; Aim. Identification of morphological patterns of placental lesions associated with preeclampsia.&#x0D; Materials and methods. A retrospective morphological study of 355 placentas sent for histological examination in the period from 2015 to 2020 was carried out. During the analyzed period, 184 placentas from pregnancies with an established diagnosis of preeclampsia and 171 placentas from pregnancies with a physiological course were studied.&#x0D; Results. It has been established that preeclampsia is associated with a smaller mass, size and height of the placenta. As morphological patterns associated with preeclampsia, such histological signs of maternal vascular malperfusion, such as infarcts, arterial atherosclerosis, etc., were identified.&#x0D; Conclusions. The heterogeneity of clinical and histological signs associated with both the physiological and pathological course of pregnancy reflects the different gestational age of the onset of the disease and the stage of development of the adaptive capabilities of the placenta. Identification of morphological patterns associated with hypoxic damage to the fetus allows us to identify a group of newborns with a high risk of chronic hypoxic damage in the perinatal period and to stratify the risk group in the postnatal period in order to reduce infant morbidity and mortality.

Aromatic Amino Acids: Phenylalanine and Tyrosine in Patients with Hypertension and Coronary Artery Disease

Aim. To evaluate changes in the profile of aromatic amino acids (AAA) in patients with cardiovascular diseases (CVD): hypertension and coronary artery disease (CАD) in comparison with healthy study participants.Material and methods. One hundred and thirty-one participants were included in the study: 58 participants were included in the hypertension group, 46 in the CАD group, and 27 participants without signs of CVD in the control group. We used ultrahigh-performance liquid chromatography in combination with a triple quadrupole analyzer to measure plasma AAA: phenylalanine and tyrosine (Phe, Tyr) in all study participants. The association of AAA with biochemical blood test parameters, echocardiography (EchoCG) parameters, blood pressure level and clinical characteristics was analyzed.Results. A statistically significant difference in the level of concentration of Phe and Tyr was revealed (p=0,002 and p=0,024, respectively), comparing the three groups. Post-hoc analysis showed differences in the circulating level of both amino acids in patients with CAD vs the control group (Phe p=0,008 and Tyr p=0,020). Also a statistically significant difference in the level of Phe of the hypertension and CАD groups (p=0,017) was found. A negative correlation of low-density lipoproteins (LDL) with the level of Phe (r=-0,685, p&lt;0,05) and Tyr (r=-0,583, p&lt;0,05), as well as the level of Phe with total cholesterol (r=-0,461, p&lt;0,05) was found in the group without CVD. In the hypertension group, only a weak positive correlation was found between very low-density lipoproteins and AAA levels (Phe r=0,326 and Tyr r=0,365, p&lt;0,05), while in patients with CAD, the level of Phe and Tyr was negative correlated with high-density lipoprotein (r=-0,378 and r=-0,543, respectively, p&lt;0,05), and the level of Tyr with LDL (r=0,349, p&lt;0,05). When isolating the group with proven atherosclerosis of peripheral and/or coronary arteries, a statistically significant difference was revealed between the group of patients with CVD and clinical and instrumental signs of atherosclerosis and the group of patients with CVD without proven atherosclerosis in Phe level (p=0,019).Conclusion. Concentrations of AAA were higher in patients with CVD, comparing with the control group. At the same time, an increase of the Phe level was associated with the presence of peripheral or coronary atherosclerosis. The revealed correlations of AAA with EchoCG parameters and lipid spectrum parameters require further study to understand the involvement of AAA in pathogenesis of CVD and its potential role as treatment target.

Post-mortem evidence of a diverse distribution pattern of atherosclerosis in the South African population

Cardiovascular diseases (CVDs) are the number one cause of mortality worldwide. The disease profile of CVD varies considerably between different demographic groups and socioeconomic status. Atherosclerosis remains a major risk factor for CVD, and thus, believed to be a good indicator of the CVD profile in a population, yet little is known on its prevalence in sub-Saharan African populations. We aimed to determine the prevalence of atherosclerosis in a diverse South African population as found with post-mortem investigations. A retrospective file-audit was done on 10,240 forensic post-mortem reports done at a forensic pathology mortuary in South Africa, over 10-years. European descent males had the highest prevalence, with roughly one-quarter having coronary artery (CA) or large vessel (LV) atherosclerosis. European descent females followed closely, with one-fifth of the population having CA atherosclerosis and approximately a quarter having LV atherosclerosis. African descent males and females had a substantially lower prevalence in atherosclerosis for both CAs and LVs than European descendants. The mixed-ancestry population had a slightly higher prevalence of atherosclerosis in CAs and LVs than in the African population; however, it was still far lower than the European group. Some deviations in prevalence were noted within certain groups over the course of 10-years. The substantial difference in prevalence of atherosclerosis shows that in our region a diverse distribution pattern between ethnic groups and genders is present. However, follow-up studies are required to elucidate aetiological factors in cardiovascular health in our region.

Biomarkers of Apoptosis and Cell Proliferation in Diagnosing the Progression of Atherosclerosis in Different Vascular Pools

INTRODUCTION: The development and progression of atherosclerosis in different vascular pools remain unclear. Many studies have considered apoptosis to play a key role in the development of atherosclerosis; apoptosis is a programmed cell death with characteristic morphological signs aimed at providing homeostasis in an organism in general and in the vascular wall in particular. However, all studies that have been devoted to markers of apoptosis were mostly experimental and were conducted on either animals or grown cultures of different cells. The study aimed to examine markers of apoptosis (р53, sFas, Вах, and Всl-2) and proliferation (platelet-derived growth factor [PDGF] BB) in the vessel wall in the area of an atherosclerotic lesion in a patient with multifocal atherosclerosis. The clinical case was of interest because it allowed the assessment of biomarkers in both the area of progression of atherosclerotic lesion on an operated limb and the carotid pool in the long-term postoperative period.&#x0D; CONCLUSIONS: This case demonstrated that a patient with obliterating atherosclerosis of the lower limb arteries had an elevated level of pro-apoptotic markers р53 and Вах and PDGF ВВ as a marker of cell proliferation and migration, against the background reduced level of anti-apoptotic markers Всl-2 and sFas in comparison with their values in the normal arterial wall. The progression of atherosclerotic lesion in two vascular pools was associated with a further increase in the values of proapoptotic markers (р53 and Вах) and decrease in the values of Всl-2 and sFas compared with the initial samples. With this, the values of PDGF ВВ marker remained elevated relative to the initial level.

Influence of risk factors for the development of cardiovascular diseases on the parameters of arterial stiffness in patients with arterial hypertension and atherosclerosis of different degrees of severity

BACKGROUND: Arterial hypertension is widespread in the population, leads to the development of arteriosclerosis and increase of arterial stiffness, and is the main non-lipid risk factor of atherosclerosis development. Multiple studies have shown that increase of arterial stiffness is an independent risk factor for the development of cardiovascular events. However, the influence of traditional cardiovascular risk factors on arterial stiffness in arterial hypertension and atherosclerotic process of different degrees of severity has not been sufficiently studied.&#x0D; AIM: To assess the influence of traditional risk factors on the parameters of arterial stiffness in patients with arterial hypertension (AH) and atherosclerotic process of varying degrees of severity.&#x0D; MATERIALS AND METHODS: 133 subjects with AH have been divided into 3 groups depending on the severity of the atherosclerotic process. The control group included 33 individuals without known cardiovascular diseases. All the participants have undergone a standard clinical and laboratory examination, 24hr blood pressure monitoring with assessment of arterial stiffness (AS) parameters. The influence of risk factors on AS parameters has been analyzed for all the participants and separately by groups.&#x0D; RESULTS: In the AH patients, an increase in the arterial stiffness index (ASI) is associated with an older age and an increase in systolic blood pressure (SBP); an increase in the augmentation index (AIx75) is associated with age; SBP in higher in women. Pulse wave velocity in the aorta (PWVao) is most associated with age, smoking, and family history in patients with hypertension and subclinical atherosclerosis. An increase in AIx75 is associated with an older age and is higher in women, while ASI has a positive relationship with age and SBP. In patients with hypertension and coronary artery disease, there is a positive correlation between male body mass index and PWVao. The increase in ASI in this group is associated with female gender, SBP and age. In individuals without hypertension and signs of atherosclerosis with a family history of CVD, PWVao values are higher than in similar individuals without a family history of CVD.&#x0D; CONCLUSIONS: In the group of all the participants, female gender, smoking, an older age, SBP, and body mass index are associated with increased AS parameters. The association between risk factors and parameters of arterial stiffness has peculiarities in patients with hypertension with varying degrees of severity of the atherosclerotic process.