Intimal Thickening Research Articles

The protective effect and potential mechanism of Zanthoxylum bungeanum Maxim. on atherosclerosis.

The pericarp of Zanthoxylum bungeanum Maxim. (ZBM) is an edible spice with medicinal value, and it has anti-obesity, anti-inflammatory, and cardiovascular protective effects. This study investigated the therapeutic effect of ZBM on atherosclerosis (AS) and its potential mechanisms. An in vivo experimental model of AS was established on apolipoprotein-E deficient (ApoE-/-) mice to evaluate the efficacy of ZBM. Serum metabolomics combined with the vascular smooth muscle cell (VSMC) proliferation model were subsequently conducted to analyze the mechanisms. Results showed that ZBM effectively alleviated blood lipid disorders, aortic lipid accumulation, and intimal thickness in mice. Metabolomics indicated that ZBM mainly regulated 5 major metabolic pathways, including TCA cycle, steroid hormone biosynthesis, sphingolipid metabolism, glyoxylate and dicarboxylate metabolism, glycerophospholipid metabolism, which affected lipid metabolism and cell proliferation. Further experiments showed that ZBM inhibited VSMC proliferation likely because it blocked the signal transducer activator of transcription 3 (STAT3) phosphorylation and activated nuclear factor E2-related factor-2 (Nrf2)/heme oxygenase-1 (HO-1) pathway, resulting in G0/G1 phase arrest and reactive oxygen species (ROS) clearance.

Delivery of N-Cadherin Targeting Peptides to Vascular Tissues by Surface-Modified Polyurethane Nanoparticles via a Drug-Coated Balloon.

Restenosis remains a long-standing limitation to effectively maintain functional blood flow after percutaneous transluminal angioplasty (PTA). While the use of drug-coated balloons (DCBs) containing antiproliferative drugs has improved patient outcomes, limited tissue transfer and poor therapeutic targeting capabilities contribute to off-target cytotoxicity, precluding adequate endothelial repair. In this work, a DCB system was designed and tested to achieve defined arterial delivery of an antirestenosis therapeutic candidate, cadherin-2 (N-cadherin) mimetic peptides (NCad), shown to selectively inhibit smooth muscle cell migration in vitro and limit intimal thickening in early animal PTA models. To enable successful tissue transfer in the current work, a nanoparticle excipient system previously demonstrated to be an effective carrier of NCad in vitro was integrated with customized DCB coating methodologies designed to prevent therapeutic loss during delivery. DCB design took into consideration four components: (1) the angioplasty balloon; (2) a poly(ethylene oxide) (PEO) monolayer acting as a hydrophilic spacer between the balloon surface and the nanoparticles to assist with improved nanoparticle release; (3) surface-modified degradable polar hydrophobic ionic polyurethane (D-PHI) nanoparticles loaded with NCad to facilitate the transport of the therapeutic peptide into vascular tissue; and (4) a PEO sacrificial coating applied over the nanoparticle excipient layer to prevent premature losses during transit to the artery. The nanoparticle-DCB platform successfully delivered NCad to rat carotid tissue, with superior efficacy and increased permeation within the vessel wall compared with soluble NCad infusion alone. Nanoscale technologies in conjunction with enhanced DCB design properties hold promise in advancing the localized delivery of preventive restenosis therapies in vascular disease.

Duplex Ultrasonography for Screening and Monitoring of Carotid Artery Stenosis for Risk Stratification of Ischemic Stroke

Aim: To evaluate the efficiency of Duplex Ultrasonography (DUS) for monitoring and screening of Carotid Artery Stenosis (CAS).Methods: PubMed, Web of Science, Cochrane, and SCOPUS were searched for relevant articles. The quality assessment of the included studies was conducted according to the Cochrane Risk of Bias Tool.Results: Our meta-analysis included six articles. Carotid DUS could detect mild CAS in 25%, moderate CAS in 13%, severe CAS in 14.5% of the examined vessels, detection of carotid artery plaques in 36.5% of the examined vessels, and abnormal intima thickness in 21.5% of the examined vessels.Conclusion: DUS is an important exam in the identification of patients with symptomatic CAS. It can improve clinical practice and provide cost-effective management for CAS. Carotid DUS showed high specificity and sensitivity in the diagnosis of CAS, especially a severe degree of stenosis.

Comparison of Histomorphometric Characteristics of Heart and Aorta in Young Adult and Aged Rats

Aim: The aim of this study was to compare the histomorphometric and immunohistochemical properties of the heart and aorta in young adult and aged rats. Material and Methods: Sixteen female Wistar albino rats, eight young adult (6 months old, female, 233.25±13.85 g) and rats were used in the study. The rats were sacrificed under high dose anaesthesia and heart and aortic tissues were collected. Ventricular and septum interventiculare thicknesses were measured on the heart tissues, tunica media, tunica intima thickness and aortic diameter were measured histomorphometrically on the aortic tissues. In addition, Inducible Nitric Oxide Synthase (iNOS) in the smooth muscle cells of the tunica media of the aorta and occludin protein levels in the aorta and heart endothelium were examined by immunohistochemical method and histological scoring was performed. Results: As a result of statistical analysis, body weight, heart weight, heart weight/body weight ratio, tunica media and intima thicknesses, and aortic diameters were found to be statistically significantly higher in aged rats compared to young adult rats (p

Correlation between the mechanism of arteriopathy in IgA nephropathy and blood stasis syndrome: A cohort study.

To investigate the correlation between blood stasis syndrome and arteriopathy in immunoglobulin A nephropathy (IgAN). Wall thickness/outer vessel diameter, intimal thickness/outer vessel diameter, and medial thickness/outer vessel diameter were measured using ImageJ software. Vascular endothelial-derived growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), proliferating cell nuclear antigen (PCNA), extracellular signal-regulated kinase (ERK) 1/2, and nuclear factor kappa B (NF-κB) were detected by immunohistochemical staining. Twenty-four-hour urine protein quantification, serum creatinine, urea nitrogen, and uric acid were collected. Blood stasis syndrome and vessel scores were calculated based on Katafuchi's grade. Intimal thickness/outer vessel diameter (0.2725 ± 0.0932 μm), medial thickness/outer vessel diameter (0.2747 ± 0.1139 μm), and wall thickness/outer vessel diameter (0.6136 ± 0.1120 μm) were the largest in IgAN with arteriopathy group. VEGF (0.35 ± 0.90), MMP-9 (0.38 ± 0.12), PCNA (0.43 ± 0.12), ERK1/2 (0.31 ± 0.11), and NF-κB (0.37 ± 0.14) were the highest in IgAN with arteriopathy group. Intimal thickening of IgAN was moderately positively correlated with VEGF, MMP-9, PCNA, ERK1/2, and NF-κB (0.5 < r < 0.8). Medial thickening of IgAN was moderately positively correlated with PCNA and NF-κB (0.5 < r < 0.8). Wall thickening of IgAN was lowly positively correlated with VEGF and MMP-9 (0.3 < r < 0.5). Blood stasis syndrome score was associated with vessel score in IgAN with arteriopathy (P < 0.05). Blood stasis syndrome score can assess the degree of pathological changes.

Enhancing small diameter tissue engineered vascular grafts with heparin and hepatocyte growth factor: A promising approach.

Currently, there is often a lack of suitable small-caliber graft vessels for treating cardiovascular diseases because of thrombosis and intimal hyperplasia. Tissue engineered vascular grafts (TEVGs) promise a potential solution to this issue. Acellular vascular matrix with good mechanical properties and biocompatibility is commonly used as a tissue engineered scaffold. In this study, acellular rat aortas were preloaded with heparin and hepatocyte growth factor (HGF) to fabricate small diameter TEVGs. In terms of the biomechanical properties, this scaffold was similar to native rat aortas. We implanted this scaffold into a rat abdominal aorta, and the acellular aorta with heparin only was used as control. The patency at 6 months of the two groups was 100%. At 1 month, a complete layer of endothelial cells could be seen on the surface of the vascular lumen of the scaffold with heparin and HGF. The results also showed that the intimal thickness was significantly reduced in the grafts coated with HGF compared to the control grafts. In conclusion, the small-diameter TEVGs constructed by acellular vascular scaffolds coated with heparin and HGF have a promising clinical application prospect.

Risk Factors Favoring Plaque Erosion.

Plaque erosion is the second leading cause of coronary thrombosis following plaque rupture and represents a key pathophysiological process underlying acute coronary syndromes that can culminate in sudden coronary death. While the precise mechanisms and risk factors driving plaque rupture are well-established, those for erosion have only recently been explored. This review summarizes current literature on the characteristics and risk factors favoring plaque erosion. Plaque erosion is characterized by a defective endothelial layer in the intima, promoting thrombus formation in the presence of an intact fibrous cap. It is more common in younger women (< 50 years) and smokers. Pathologic intimal thickening or fibroatheroma are common underlying lesions. Risk factors include gender, age, smoking, and disturbances in shear flow. Advances in pathogenic and molecular mechanisms, such as endothelial shear stress, neutrophil activation, and toll-like receptor-2 pathways, are discussed. Understanding the major risk factors for plaque erosion can inform diagnostics and therapeutics to prevent the progression of arterial thrombosis.

The Effect of Standardized Mangosteen Skin Extraction, Nano-emulsion, Nano-chitosan and Treadmill Exercise on Atherogenic Rat Model

Background: Atherosclerosis, the most common cause of CVD, is associated with oxidative stress and cholesterol. Antioxidant and regular physical exercise have been considered as the probable interventions to dampen the process. The pericarp of mangosteen (Garcinia mangostana Linn) is known for containing a high amount of xanthones including α-mangostin with antioxidant effects. The current study investigates the anti-atherogenic potential of mangosteen skin extract in nano-emulsion and nano-chitosan formulations, singly and in combination with treadmill exercise, versus the statin, Atorvastatin. Methods: A randomized controlled trial was conducted on 30 male Wistar rats, divided into six groups: normal diet control (C1), atherogenic diet control (C2), and four treatment groups receiving an atherogenic diet plus treadmill exercise combined with Atorvastatin (T1), standardized mangosteen extract (T2), mangosteen nano-emulsion (T3), or mangosteen nano-chitosan (T4). The aortic tunica intima and tunica intima-media thickness were measured histologically after 56 days. Results: The aortic intimal thickness was noticeably higher in the atherogenic diet group (C2: 12.13±1.87 mm) compared to the normal diet group (C1: 4.27±0.75 mm). In the treatment groups, the intimal thickness ranged from 2.97±0.45 mm to 4.17±1.70 mm and showed no significant differences from the normal diet group. A similar pattern was seen in the intima-media thickness, with 145.63±17.12 mm recorded for the normal diet group and values ranging from 106.90±10.41 mm to 135.90±12.63 mm in the treatment groups, again without significant differences. Survival analysis using Kaplan-Meier curves showed clear differences between the groups (p &lt; 0.001). The untreated atherogenic diet group (C2) had the poorest survival, with no rats surviving until the study's conclusion. In contrast, survival improved in all treatment groups, with the Mangosteen Nano-chitosan (T4) group and the normal diet group (C1) achieving the best outcomes, as all rats in these groups survived. Conclusion: Mangosteen skin extracts, whether in nano-emulsion or nano-chitosan forms, combined with treadmill exercise, showed significant differences in maintaining the survivability of rat with atherogenic-induced diet despite no significant differences in preventing atherogenesis compared to Atorvastatin or a normal diet. Further research is needed to confirm these potential therapeutic effects.

Abstract 4146316: Venous Remodeling and Occlusion Accompany Arterial Pathology in Patients with Chronic Limb Threatening Ischemia

Background: Chronic limb threatening ischemia (CLTI) is defined as the presence of peripheral artery disease (PAD) in combination with rest pain or tissue loss and represents advanced arterial occlusive disease. Little is known about associated venous pathology as prior pathologic reports were limited to evaluation of maximally diseased arterial lesions. Objectives: To characterize arterial and venous histopathology in patients with CLTI. Methods: Tissue containing peripheral arteries and veins from the femoropopliteal to distal tibial arteries was harvested from 10 patients who underwent amputation for CLTI (Fig 1). Vessels were sectioned at 0.5 cm intervals, and histopathologic features were catalogued across 535 arterial and 493 venous sections. Results: Consistent with PAD, atherosclerotic lesions were more prevalent in proximal than distal arteries; 81.8% (27/33) femoropopliteal sections compared to 26.6% (134/502) of tibial sections. Severe stenosis (&gt;90%) was noted in 21.9% (117) of sections and was associated with atherosclerosis (pathological intimal thickening, fibroatheroma, fibrocalcific or fibro-osseous lesions) in 10.3% (12), luminal thrombi in 68.4% (80), or both in 21.4% (25) of arterial sections. In all patients and in 99.0% (488/493) of venous sections, irrespective of the degree of arterial luminal stenosis, adjacent large (≥1000µm) and small diameter veins revealed marked thickening of the vessel wall comprised of fibrosis and smooth muscle hyperplasia (Fig 2). While large veins retained luminal patency, small veins exhibited severe luminal stenosis or obliteration. Venous thrombosis was uncommon, occurring in 3.0% (15/493) of sections. Conclusions: Venous remodeling with stenosis and occlusion is highly prevalent and coincides with arterial disease pathology in patients with CLTI. This novel finding of previously underappreciated and severely altered venous pathology suggests a possible additional mechanism for limb ischemia in CLTI.

Abstract 4121527: Empagliflozin Improves Mitochondrial Biogenesis in Pulmonary Arterial Hypertension

Background: Pulmonary arterial hypertension (PAH) is a devastating disease characterized by endothelial proliferation and progressive pulmonary vascular (PV) remodeling. Empagliflozin (EMPA), a sodium glucose cotransporter 2 (SGLT2) inhibitor, benefits heart failure patients, potentially mediated by improved mitochondrial function. This study aimed to explore the impact of EMPA in PAH. Methods and Results: Immunohistochemistry of pulmonary arteries revealed the expression of SGLT2 in the intima of PAH patients. Microvascular endothelial cells (MVECs) were isolated from lungs of control subjects (CTRL) and PAH patients and found intense expression of SGLT2 in PAH MVECs. Western blot showed significantly higher expression of SGLT2, while PGC-1α, a transcriptional coactivator known as a master regulator of mitochondrial biogenesis, was lower in PAH MVECs compared to CTRL (Image 1). PAH MVECs were treated with EMPA (1 μM) and observed a significant increase of PGC-1α and BMPR2-pSmad1/5/9. Similarly, knockdown of SGLT2 using siRNA resulted in enhanced expression of PGC-1α. Moreover, Seahorse analysis revealed increased oxygen consumption rate and reduced extracellular acidification rate by EMPA, suggesting that EMPA improved mitochondrial respiration. In addition, EMPA attenuated reactive oxygen species and proliferation of PAH MVECs, as revealed by MitoTracker analysis and MTT assay respectively. For the in vivo study, Sprague-Dawley rats (120-180 gram) were injected with SU5416 (Week-0) and exposed to hypoxia for 3 weeks followed by normoxia. After randomization at Week-4, rats were treated with EMPA (300 mg/kg in chow, n=12) or placebo (PLAC, n=12). Catheterization and histological analysis were performed at Week-8. EMPA decreased PV resistance index (0.21±0.02 vs. 0.37±0.05 mmHg/mL/min/mm 2 , p=0.01), ameliorated intima thickening (21.0±7.5 vs. 40.0±7.8%, p&lt;0.01) and vessel occlusion (Image 2). We further conducted a single-center, open-label, single-arm interventional proof-of-concept study to assess the tolerability of 12 weeks of treatment with 10mg of EMPA as add-on therapy in eight patients with a prior PAH diagnosis. There were no treatment related adverse events during the study time course. Conclusions: EMPA directly improved mitochondrial biogenesis and attenuated proliferation of MVECs from PAH patients and reversed PV remodeling in experimental PAH. EMPA treatment was feasible in patients with PAH. EMPA may serve as a new therapeutic option for PAH.

Analysis of influencing factors of clinical pregnancy rate in second cycle intrauterine insemination.

To explore the factors influencing the clinical pregnancy rate in the Reproductive Center of the Affiliated Hospital of North Sichuan Medical College in the second cycle, a retrospective analysis of the clinical data of 175 patients who underwent the second cycle of intrauterine insemination (175 cycles) from July 2019 to July 2022 was performed. According to whether the patients reached clinical pregnancy, they were divided into the pregnant group (32 cycles) and non-pregnant group (143 cycles). The age, infertility years, infertility factors, infertility type, number of sinus follicles, intimal thickness, intimal type, basal follicle-stimulating hormone, basal luteinizing hormone, basal estradiol, stimulation regimen, season, body mass index, and male semen quality were statistically analyzed between the 2 groups. The number of intrauterine insemination (IUI) in the second cycle was 175, and the clinical pregnancy rate was 18.3% (32/175). The age of the pregnant group was lower than that of the non-pregnant group [(26.7 ± 1.07) vs (30.56 ± 0.51), P = .05]. The clinical pregnancy rate in patients aged ≤30 years was significantly higher than that in patients aged > 30 years [28.6% vs 7.1%, P < .05]. Among infertility factors, the pregnancy rate of patients who underwent IUI due to female factors was significantly higher than that of male factors, combined factors (both male and female), and unexplained infertility, and the differences were statistically significant [37.1% vs 22.4%, 18.2%, 3.2%, P < .05]. In multivariate logistic regression analysis, age and infertility factors were independent influencing factors of clinical pregnancy rate in the second cycle of IUI. In, while in artificial insemination, female age and infertility factors were important factors affecting the clinical pregnancy rate of the second cycle of IUI. If the outcome of the first cycle is not pregnant, the female age is <30 years, infertility is the female factor, and the second cycle of IUI can be considered.

Exendin-4, a glucagon-like peptide-1 receptor agonist, regulates ductus arteriosus by vasodilation and anti-remodeling through the PKA pathway

The mechanisms of ductus arteriosus (DA) closure involve vasoconstriction and vascular remodeling. Previous findings indicate that the glucagon-like peptide-1 receptor agonist (GLP-1RA) exhibits antihypertensive and anti-remodeling effects in the pulmonary circulation. However, its role in the DA remains unknown. This study aimed to investigate whether exendin-4 (Ex-4), a GLP-1RA, can regulate DA patency and elucidate its mechanisms. After confirming the presence of GLP-1R in neonatal rat DA tissue in vivo, the effects of Ex-4 on DA patency in neonatal rats were sequentially examined. Two hours after birth, we observed spontaneous closure of the DA in control rats. In contrast, Ex-4 prevented the closure of DA, accompanied by reduced intimal thickening. Ex-4 attenuated oxygen-induced vasoconstriction in isolated DA rings ex vivo. This effect was diminished in the presence of H89, a PKA inhibitor. In vitro, Ex-4 inhibited platelet-derived growth factor (PDGF)-BB-induced proliferation and migration of DA smooth muscle cells. Additionally, Ex-4 inhibited PDGF-BB-induced reactive oxygen species (ROS) production, calcium mobilization, and signal transduction of MAPK and Akt pathways. Furthermore, Ex-4 preserved the nuclear expression of Nrf2 attenuated by PDGF-BB. Similarly, all these in vitro effects of Ex-4 were blunted by H89. In conclusion, Ex-4 maintains postnatal DA patency through vasodilatation and anti-remodeling via the PKA pathway. The GLP-1R/PKA pathway emerges as a promising target of DA patency in clinical management.

Identification of clinical risk factors for coronary artery lesions in children with Kawasaki disease: a retrospective cohort study.

Coronary artery lesions are the most severe complications of Kawasaki disease. Despite recent advances, evidence of the association between risk factors and coronary artery lesion is lacking. In this study, we demonstrated the potential clinical indicators that could assist to evaluate the prevalence of coronary artery lesion among paediatric patients with Kawasaki disease. We retrospectively enrolled 260 paediatric patients with Kawasaki disease. Patients with coronary dilation, coronary aneurysm, and intimal thickening of coronary arteries were included in this study. Medical records of each patient were collected. Logistic regression analysis was performed to explore risk factors and the occurrence of coronary artery lesion in patients with Kawasaki disease. Respectively, 64 (24.6%), 39 (15%), and 56 patients (21.5%) of the participants had coronary dilation, coronary aneurysm, and intimal thickening of coronary arteries. Univariate analysis revealed that age, gender, duration of fever, time of initial use of intravenous immunoglobulin, erythrocyte sedimentation rate, white blood cell counts, time of platelet increase, the maximum value of platelet, albumin, and immunoglobulin G level was associated with coronary artery lesion. In multivariable logistic analysis, those younger and mainly males were associated with all three outcomes of coronary artery lesion, lower serum albumin levels, and later initial use of intravenous immunoglobulin were linked to a higher risk of coronary dilation and coronary aneurysm. The potential risk factors that could be used to estimate the occurrence of coronary artery lesion in Kawasaki disease patients are young age, male, lower serum albumin lever, and later initial use of intravenous immunoglobulin. However, long-term follow-up and multi-centre studies are required to verify our findings in the future.

Burden of atherogenic lipids and association with cardiac allograft vasculopathy in heart transplant recipients,

BackgroundCardiac Allograft Vasculopathy (CAV) is a leading cause of morbidity and mortality after heart transplantation. There are limited contemporary studies examining post-transplant lipid management and cardiometabolic health. ObjectiveWe study the burden of cardiometabolic derangements post transplantation and its impact on CAV in a modern cohort of heart transplant recipients. MethodsAll heart transplant (HTx) recipients between January 2019 and December 2020, with two lipid assessments and angiographic surveillance were included. Logistic regression was used to assess association of lipid levels with cardiovascular outcomes and CAV. ResultsAmong 87 HTx recipients, atherogenic lipids were significantly elevated after Htx. Median LDL-C increased from a baseline level of 69.5 mg/dL to 86.5 mg/dL, p = 0.002, non-HDL-C 91.5 mg/dL to 118 mg/dL, p < 0.001, triglycerides 94.5 mg/dL to 133 mg/dL, p < 0.001, and remnant cholesterol 19 mg/dL to 27 mg/dL, p < 0.001. Increases in non-HDL-C, triglycerides, and remnant cholesterol were significantly associated with increased risk of CAV (Stanford Grade 4 and intimal thickness). Increases in triglycerides and remnant-C were associated with increased risk of composite major adverse cardiovascular events. ConclusionWe demonstrate a significant increase in atherogenic lipids two years following transplantation with low use (20 %) of high-intensity statin. Increase in atherogenic lipids was associated with increased risk of CAV and increase in triglycerides and remnant cholesterol with increased MACE. Future studies examining cardiometabolic consequences of heart transplantation and optimal treatment strategies to reduce risk of CAV and MACE are needed.

Carotid Atherosclerosis in Diabetic Patients and Associated Risk Factors

Objective: To determine the frequency of carotid atherosclerosis in diabetic patients and find out its association with various risk factors. Study Design: Cross-sectional analytical study. Place and Duration of Study: Department of Medicine, Combined Military Hospital, Nowshera Pakistan, from May to Jul 2022. Methodology: Patients, from both genders, were included in this study. Demographic information was obtained from all patients. Patients fulfilling the inclusion and exclusion criteria underwent carotid Doppler ultrasound after giving informed consent. High-resolution 7.5 MHz probe B mode ultrasonography and atherosclerosis was classified on the basis of grey-scale imaging. Results: A total of 100 patients were included in the study, out of which 74 were males and 26 were females. Among diabetics, 54% occurrence of atherosclerosis was seen, with a major share of 24% involvement of the left carotid artery, followed by 18% bilaterally, and 12% right carotid artery involvement. Carotid intimal media thickness increased with advancing age, with variable severity of mild in 32%, moderate in 14%, and severe stenosis in 3% of positive cases. Conclusion: There was a high association of carotid atherosclerosis with diabetes mellitus, having significant association with older age, hypertension, hyperlipidemia, and smoking.

Is aortic elasticity associated with hydration status in stage of chronic renal disease in children?

Objective: We aimed to evaluate cardiovascular risks and influencing factors by measuring aortic elasticity parameters and carotid intima thickness in children with cronic kidney disease (CKD), and also evaluated the hydration status of patients with bioimpedance spectroscopy (BIS) measurements and investigated the effect of hydration status on vascular functions. Patients and Methods: The study group included an average of 13.3 ± 3.7 years (16 girls and 22 boys, 38 CKD patients), control group on average 12.1 ± 2.9 (16 girls and 15 boys, 31 healthy children). Systolic and diastolic diameters of the aortic annulus and aorta at each level were obtained; z-scores, aortic strain, distensibility, stiffness index were calculated. Carotid intima-media thickness and flow – mediated dilatation were studied. Bioimpedance spectroscopy was performed to all patients. Results: Interventricular septum and left atrial (p=0.002, p=0.013), sinus valsalva and sinotubular junction z scores (p=0.009, p=0.012) were found to be higher and distensibility and strain decreased, stiffness index increased in the abdominal aorta of patients with CKD (p=0.007, p=0.002, p=0.004). Patients with CKD had statistically significant over-hydration. Conclusion: Vascular wall changes that affect the elastic properties of the aortic wall begin to develop in childhood in patients with CKD.

Imaging human coronary cholesterol/urate crystals with cross-polarized micro-optical coherence tomography.

Birefringent crystals such as monosodium-urate (MSU) and cholesterol crystals (CC) likely contribute to the progression of coronary artery disease (CAD) due to their potential to exacerbate inflammation through inflammatory cytokine activation. Here, we present cross-polarized micro-optical coherence tomography (CP-µOCT) for visualizing individual birefringent crystals in human coronary arteries. Human cadaver coronary arteries with a history of CAD with or without gout were dissected for CP-µOCT imaging. Specimens were processed for histological identification of birefringence under polarization light microscopy (PLM). CP-µOCT visualized needle-crystals that appeared as long projections in orthogonal planes, and PLM confirmed that CP-µOCT-delineated needle-crystals demonstrated negative birefringence. The needle-crystals were dissolved after immersion in uricase (p < 0.05), and thus were MSU. CP-µOCT was three-dimensionally volume-rendered for counting MSU and CCs in 79 regions of interest sized [750 (x) × 500 (y) × 400 (z) µm]. Crystal counts were normalized by the total coronary length utilized. The relationship between CP-µOCT-delineated MSU counts and those seen in corresponding histology, and the difference in coronary MSU amongst gout vs. non-gout patients was analyzed. CP-µOCT-delineated MSU counts were significantly correlated with MSU counted by PLM-based histology (R = 0.98, p < 0.01), and with histology-derived intimal thickening (R = 0.51, p < 0.01). MSU and CCs were both significantly greater in gout patients compared with non-gout patients (p < 0.05). These results demonstrate a significant increase in CP-µOCT-delineated crystals in gout vs. non-gout patients, suggesting that this technology can be used to improve our understanding of crystal-driven coronary pathogenesis.

Moyamoya disease: insights into the clinical implications of the RNF213 gene

Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by progressive stenosis of the terminal internal carotid arteries and the formation of compensatory collateral vessels, which appear as a “puff of smoke” on cerebral angiography. It is a significant cause of stroke in East Asia, with an incidence of 0.5 to 1.5 cases per 100,000 people annually. The etiology of MMD remains unclear; however, the identification of the RNF213 gene, particularly the R4810K variant, as a major susceptibility factor among the East Asian population, has provided crucial insights into the disease's pathophysiology and clinical manifestations. MMD typically presents with transient ischemic attacks, ischemic and hemorrhagic strokes, seizures, headaches, and cognitive deficits. Diagnostic criteria have evolved to emphasize advanced imaging techniques. Pathological features include fibrocellular intimal thickening, irregular undulation of the elastic lamina, and the formation of moyamoya vessels. The mutation in the RNF213 gene impairs the degradation of proteins involved in vessel development, leading to abnormal angiogenesis. Genotype-phenotype studies indicate that the RNF213 variant is associated with an earlier onset, transient ischemic attacks, infarctions, and involvement of the posterior cerebral artery, although its effects vary between regions. Additionally, the homozygous RNF213 variant consistently correlates with an earlier age of onset and a higher risk of cerebral infarction. However, further research is necessary to fully understand its long-term impacts and its relationship with revascularization outcomes. Ongoing research is crucial to fully comprehend the pathophysiology and genetics of MMD, improve prognostic predictions, and develop novel therapies.

Plaque phenotyping using deep learning in optical coherence tomography imaging

Abstract Background Artificial intelligence (AI) techniques have emerged as powerful tools in various computer vision tasks, particularly in classification, detection, and segmentation. Purpose This study aimed to develop a deep learning model for categorizing optical coherence tomography (OCT) frames into different plaque phenotypes, including thin-cap fibroatheroma (TCFA) and fibroatheroma. Methods A prospective multicenter observational study enrolled 168 patients who underwent percutaneous coronary intervention (PCI) and received OCT imaging for non-target lesions with angiographically estimated diameter stenosis greater than 30% (177 vessels). Among them, 129 patients (135 vessels) underwent follow-up OCT imaging at 1 year. A total of 45,072 OCT frames were randomly divided into training and validation sets in a 4:1 ratio. An EfficientNet-B3 convolutional neural network model was developed to classify OCT frames into TCFA, thick-cap fibroatheroma, non-fibroatheroma, adaptive intimal thickening, and normal vessel categories. Results A confusion matrix comparing manually assessed plaque phenotypes with AI-predicted phenotypes was presented in Table. In the validation datasets (9,015 frames), the overall accuracy of the model was 85.1%. For predicting the presence of TCFA, sensitivity was 81.1%, specificity was 98.8%, positive predictive value was 63.9%, and negative predictive value was 99.5%. Regarding the presence of fibroatheroma, sensitivity was 90.3%, specificity was 89.4%, positive predictive value was 93.1%, and negative predictive value was 85.4%. Conclusions The deep learning algorithm demonstrated high accuracy in detecting TCFA and fibroatheroma with excellent reproducibility. This automated process enables operators to promptly identify high-risk lesions during PCI, potentially leading to improved clinical outcomes.

Successful non-invasive imaging of the coronary artery IMT in pediatric patients with Kawasaki disease using high-resolution echocardiography

Kawasaki Disease (KD) is a multisystemic vasculitis of medium- and small-sized arteries. Abnormal intimal thickening may develop in the involved arterial area after regression of coronary artery aneurysm (CAA). Intimal dysfunction may induce local stenosis or arteriosclerosis in the future. In this case–control study, we investigated 29 consecutive KD patients [20 male, median current age, 7.9 years; median follow-up duration, 5.7 years] and a group of 29 healthy matched controls (CON) [19 male, median current age, 10.8 years]. They were assesed and compared for CAA, LVFS, GCS, GLS, coronary artery (CA) Z scores, carotid intima-media thickness (IMT) and coronary artery IMT by high-resolution transthoracic echocardiography (hrTTE). Coronary artery IMT (caIMT) was significantly higher in patients with a maximal CA Z score > 2.5 in acute KD than in CON: KD caIMT: 0.62 mm [IQR, 0.57–0.72 mm] vs. 0.53 mm [0.51–0.60 mm], p = 0.043. CAAs were found in 15 (51.7%) patients with acute KD. The maximal median LCA Z score in acute KD was 2.57z [IQR, 1.93—3.2z] and in follow-up −0.39z [IQR, −1.25 to −0.36z]. There was no significant difference in carotid IMT between KD patients and CON. Signs of CA intima-media thickening were detected by hrTTE in patients with a maximal CA Z score > 2.5 in acute KD. These data indicate that these patients may be at risk for cardiovascular sequale even in the absence of permanent CA luminal abnormalities. Therefore long-term follow-up of this group of KD patients may be required.