Chronic Vascular Disease Research Articles

Correlation Between Self-reported or Supervised Physical Activity in Noncommunicable Diseases and Comorbidities During COVID-19 Pandemic: A Systematic Review

Abstract Objective The aim of the study is to systematically identify the protective and ameliorative effects of physical activity among people with noncommunicable diseases such as diabetes, cancer, chronic respiratory disease, chronic vascular disease, hypertension, and existing comorbidities during the coronavirus disease (COVID-19) pandemic. Methods The trial is registered in the PROSPERO registry and used the PICO (population, intervention, comparison, and outcomes) strategy to perform the search strategy. Assessors analyzed related studies in the MEDLINE, PROQUEST, PubMed, Cochrane Library, CINAHL, Embase, Google Scholar, Physiotherapy Evidence, and Science Direct databases between December 2022 and January 2023. Researchers independently conducted a quality assessment of each study using a predeveloped quality assessment tool adapted from established tools for quantitative studies. Results Eighteen trials were included (chronic vascular disease–7, diabetes–4, hypertension–1, cancer–3, and chronic respiratory disease–3). The total number of individuals included in the systematic review was 780,003, and the total with or without COVID-19 was 188,435. Qualitative rating by the Newcastle-Ottawa Score for cross-sectional and cohort studies and the Physiotherapy Evidence Database scale revealed fair to good evidence for physical activity as a tool to reduce complications. Conclusions There is evidence that exercise can protect people with noncommunicable diseases during the COVID-19 pandemic. Registration: Registered with Prospero registry

Disruption of PCSK9 Suppresses Inflammation and Attenuates Abdominal Aortic Aneurysm Formation.

Abdominal aortic aneurysm (AAA) is a chronic vascular inflammatory disease without effective medications. PCSK9 (proprotein convertase subtilisin/kexin 9), a serine protease from the proprotein convertase family, has recently been associated with AAA in human genome-wide association studies. However, its role in AAA is unknown. Transcriptional and histological expression of PCSK9 was examined in AAA tissues and healthy controls. The impact of PCSK9 deletion and inhibition on AAA formation was assessed in mice with hyperlipidemia and Ang II (angiotensin II) overproduction. AAA lesion morphology was assessed by tissue staining. MMP (matrix metalloproteinase) activity was evaluated by gelatin zymography, and leukocyte-vessel wall interaction was monitored by intravital microscopy. RNA sequencing was used to characterize the downstream signaling of PCSK9. PCSK9 expression was upregulated and colocalized with macrophages in human and mouse AAAs. Pcsk9 deletion attenuated AAA formation, improved survival, and decreased systemic inflammation, without altering circulating cholesterol levels. Pcsk9 deficiency reduced aortic infiltration of macrophages and elastin degradation, without affecting vascular smooth muscle cell apoptosis and proliferation. Mechanistically, PCSK9 was essential in leukocyte-endothelium adhesion and expression of proinflammatory cytokines and MMP9 by macrophages. RNA sequencing of stimulated macrophages revealed that Pcsk9 deficiency upregulated histone deacetylase SIRT1 (sirtuin-1) and suppressed NF-κB (nuclear factor-κB) inflammatory signaling. SIRT1 inhibition attenuated the proinflammatory actions of PCSK9. Furthermore, administration of PCSK9 small interfering RNA or antibody constrained AAA formation/progression and inhibited vascular inflammation. PCSK9 critically mediates macrophage inflammation and elastin degradation, promoting AAA formation. PCSK9 inhibitors bear a promise to curtail AAA, beyond being used as cholesterol-lowering drugs.

RUNX2 is stabilised by TAZ and drives pulmonary artery calcification and lung vascular remodelling in pulmonary hypertension due to left heart disease.

Calcification is common in chronic vascular disease, yet its role in pulmonary hypertension due to left heart disease is unknown. Here, we probed for the role of runt-related transcription factor-2 (RUNX2), a master transcription factor in osteogenesis, and its regulation by the HIPPO pathway transcriptional coactivator with PDZ-binding motif (TAZ) in the osteogenic reprogramming of pulmonary artery smooth muscle cells and vascular calcification in patients with pulmonary hypertension due to left heart disease. We similarly examined its role using an established rat model of pulmonary hypertension due to left heart disease induced by supracoronary aortic banding. Pulmonary artery samples were collected from patients and rats with pulmonary hypertension due to left heart disease. Genome-wide RNA sequencing was performed, and pulmonary artery calcification assessed. Osteogenic signalling via TAZ and RUNX2 was delineated by protein biochemistry. In vivo, the therapeutic potential of RUNX2 or TAZ inhibition by CADD522 or verteporfin was tested in the rat model. Gene ontology term analysis identified significant enrichment in ossification and osteoblast differentiation genes, including RUNX2, in pulmonary arteries of patients and lungs of rats with pulmonary hypertension due to left heart disease. Pulmonary artery calcification was evident in both patients and rats. Both TAZ and RUNX2 were upregulated and activated in pulmonary artery smooth muscle cells of patients and rats. Co-immunoprecipitation revealed a direct interaction of RUNX2 with TAZ in pulmonary artery smooth muscle cells. TAZ inhibition or knockdown decreased RUNX2 abundance due to accelerated RUNX2 protein degradation rather than reduced de novo synthesis. Inhibition of either TAZ or RUNX2 attenuated pulmonary artery calcification, distal lung vascular remodelling and pulmonary hypertension development in the rat model. Pulmonary hypertension due to left heart disease is associated with pulmonary artery calcification that is driven by TAZ-dependent stabilisation of RUNX2, causing osteogenic reprogramming of pulmonary artery smooth muscle cells. The TAZ-RUNX2 axis may present a therapeutic target in pulmonary hypertension due to left heart disease.

Incidence of cardiovascular diseases among breast cancer patients: a nationwide registry study 2013-2020

Abstract Background and aims There is evidence to suggest that breast cancer (BC) treatment is associated with an increased risk of developing cardiovascular disease (CVD). Several countries have introduced clinical measures to reduce the impact of breast cancer treatment on cardiovascular function including activated breathing control during radiotherapy, lower radiation doses, and maximum anthracycline doses. The overall aim of this study was therefore to investigate whether breast cancer patients still exhibit higher rates of cardiovascular disease than the general population. Methods We conducted a registry-based cohort study using linked data from four nationwide health registries. Out study population included all Norwegian patients diagnosed with BC between 2013-2020 and matched them by age to 10 controls without BC. Health outcomes were measured from 2008 to 2021. We estimated the cumulative incidence from index date, for ten selected CVDs. For BC patients, the index date was defined as date of BC diagnosis. For controls, the index date was defined as the date of BC diagnosis for the matched BC patient. A wash-out period of 5 years was applied to identify incident cases of CVD. Results The study population included 27,535 patients with BC and 269,9994 matched controls. Median age in both groups was 62 years (IQR: 20). Prior to index date, there were no significant differences in the prevalence of heart valve disease, chronic ischemic heart disease heart failure and peripheral vascular disease in BC patients compared to controls (p>0.05) (Table 1). Hypertensive heart disease, pulmonary embolism, atrial fibrillation, and other cardiac arrythmias were more prevalent in BC patients, while angina pectoris and acute myocardial infarction were more prevalent among controls. After the index date, the incidence proportion for heart valve disease, hypertensive heart disease, pulmonary embolism, atrial fibrillation, other cardiac arrythmias, and heart failure were higher in BC patients compared to controls (p<0.001) (Table 2). No significant differences were found for angina pectoris, acute myocardial infarction, chronic ischemic heart disease, and peripheral vascular disease. Conclusion Breast cancer is still associated with an increased risk of developing several CVDs in current clinical practice, compared to matched controls without breast cancer.Baseline characteristicsIncidence of CVD

Iron Overload and Abdominal Aortic Aneurysm.

Abdominal aortic aneurysm (AAA) is a chronic vascular degenerative disease characterized by progressive segmental dilation of the abdominal aorta. The rupture of an AAA represents a leading cause of death in cardiovascular diseases. Despite numerous experimental and clinical studies examining potential drug targets and therapies, currently there are no pharmaceutical treatment to prevent AAA growth and rupture. Iron is an essential element in almost all living organisms and has important biological functions. Epidemiological studies have indicated that both iron deficiency and overload are associated with adverse clinical outcomes, particularly an increased risk of cardiovascular events. Recent evidence indicates that iron overload is involved in the pathogenesis of abdominal aortic aneurysms. In this review, we provide an overview of the role of iron overload in AAA progression and explore its potential pathological mechanisms. Although the exact molecular mechanisms of iron overload in the development of AAA remain to be elucidated, the inhibition of iron deposition may offer a promising strategy for preventing these aneurysms.

Investigation of Hemorheological Parameters in Ischemic Stroke Patients.

The aim of this study is to determine whether there are any changes in hemorheological parameters, including whole blood viscosity (WBV), plasma viscosity, erythrocyte aggregation, and erythrocyte deformability, in acute ischemic stroke patients, and to establish their relationship with stroke etiology. The study also aims to observe the changes in these parameters, if any, over time and after treatment, and to assess the correlation between risk factors for ischemic stroke and neuroimaging findings. This was a prospective observational study including 70 patients diagnosed with acute ischemic stroke within the first 3 days of the onset of symptoms and 96 healthy controls. Stroke patients were categorized based on TOAST criteria, and hemorheological parameters were measured at admission and on the fifth day post-treatment. Erythrocyte aggregation and deformability were measured using a laser ektacytometer, and viscosity assessment was conducted with a rotational viscometer. Stroke patients exhibited significant differences from the control group in aggregation amplitude, aggregation index, and aggregation half-time (p = 0.001, p = 0.013, p = 0.009, respectively) and showed elevated maximum value of elongation index (p = 0.000). No significant differences in WBV and plasma viscosity were observed between the groups. Post-treatment, the small vessel occlusion subgroup demonstrated a notable reduction in WBV. Additionally, homocysteine levels showed a positive correlation with scattered white matter lesions in basal ganglia and infratentorial regions (p = 0.002, p = 0.039, respectively). Increased predisposition to erythrocyte aggregation may contribute to the occurrence of acute ischemic stroke. Moreover, gaining the ability of erythrocytes to deform and increase blood flow may serve as a compensatory mechanism in the chronic vascular disease process. The risk factors for ischemic stroke may exhibit connections to specific areas within the brain.

Longitudinal association between depressive symptoms and cognitive function: the neurological mechanism of psychological and physical disturbances on memory.

The neural correlates underlying late-life depressive symptoms and cognitive deterioration are largely unclear, and little is known about the role of chronic physical conditions in such association. This research explores both concurrent and longitudinal associations between late-life depressive symptoms and cognitive functions, with examining the neural substrate and chronic vascular diseases (CVDs) in these associations. A total of 4109 participants (mean age = 65.4, 63.0% females) were evaluated for cognitive functions through various neuropsychological assessments. Depressive symptoms were assessed by the Geriatric Depression Scale and CVDs were self-reported. T1-weighted magnetic resonance imaging (MRI), diffusion tensor imaging, and functional MRI (fMRI) data were acquired in a subsample (n = 791). Cognitively, higher depressive symptoms were correlated with poor performance across all cognitive domains, with the strongest association with episodic memory (r = ‒0.138, p < 0.001). Regarding brain structure, depressive symptoms were negatively correlated with thalamic volume and white matter integrity. Further, white matter integrity was found to mediate the longitudinal association between depressive symptoms and episodic memory (indirect effect = -0.017, 95% CI -0.045 to -0.002) and this mediation was only significant for those with severe CVDs (β = -0.177, p = 0.008). This study is one of the first to provide neural evidence elucidating the longitudinal associations between late-life depressive symptoms and cognitive dysfunction. Additionally, the severity of CVDs strengthened these associations, which enlightens the potential of managing CVDs as an intervention target for preventing depressive symptoms-related cognitive decline.

The Role of Hybrid Revascularization Procedures for Symptomatic Chronic Peripheral Arterial Disease

Abstract Background Peripheral arterial disease (PAD) is a chronic vascular disease characterized by impaired circulation to the lower extremities. While early stages of PAD may be asymptomatic, the hallmarks of its most severe stage, known as chronic limb threatening ischemia (CLTI). It is a clinical syndrome defined by the presence of peripheral artery disease (PAD) in combination with rest pain, gangrene, or a lower limb ulceration &amp;gt;2 weeks duration. Aim of the Work The aim of this study is to assess the clinical and hemodynamic outcome of CLTI treated by hybrid revascularization procedures and the possible risk of postoperative amputation. Patients and Methods The following electronic databases were searched up to 2022: PubMed, Google Scholar search engine, Cochrane database of systematic reviews, EMBASE, Science Direct, Wiley Online Library, ELSEVIER, Scopus and the European journal of vascular society searching keywords and terms listed below: “Critical limb threatening ischemia, management of peripheral arterial disease, multi-level occlusive arterial disease, hybrid revascularization, outcome of hybrid procedures”. Results In our meta-analysis, risk factors of PAD included gender, smoking, HTN, DM, coronary artery disease, CVS, CKD, Hyperlipidemia and COPD. Success rate of hybrid revascularization technique showed a significant effect than other techniques. Conclusion The results of this meta-analysis showed that Diabetes Mellitus and hypertension are two major risk factors that worsen the outcome of hybrid procedures. Hybrid procedures have added to the armamentarium for treatment of patients with multilevel arterial disease and offer a less risky option for elderly patients with multiple comorbid conditions. Hybrid procedures are effective to treat patients with either CLI or claudication.

Severe Skin and Soft Tissue Infection of Patients Admitted to Intensive Care Units

Skin and soft tissue infections (SSTIs) can occasionally progress to life-threatening conditions, such as septic shock, requiring intensive care unit admission. Their risk factors include diabetes mellitus, chronic renal failure, chronic vascular disease, malignancy, and acquired immune deficiency syndrome. However, early diagnosis is challenging due to initially benign skin lesions and the absence of systemic symptoms such as fever. This review focuses on severe bacterial infections such as necrotizing fasciitis, gas gangrene, and toxic shock syndrome, examining their etiology and management. These severe SSTIs should be understood for the early diagnosis, appropriate treatment, and improved patient outcomes. Dermatologists play a vital role in recognizing and managing these infections

Knockdown of USP7 alleviates atherosclerosis in ApoE-deficient mice by regulating EZH2 expression.

Atherosclerosis (AS) is a chronic vascular disease associated with lipid accumulation. Understanding the molecular mechanisms of AS is essential. Ubiquitin-specific protease 7 (USP7) is a deubiquitination enzyme involved in various cellular processes, including lipid metabolism. In this study, we aimed to elucidate the role of USP7 in AS progression and its underlying mechanism using ApoE-deficient mice. We found that USP7 ablation improved the morphological characteristics of AS in these mice. USP7 knockdown reduced inflammation, evidenced by decreases in inflammatory markers IL-6, TNF-α, and IL-1β by 35, 40, and 38%, respectively (p < 0.01). Additionally, USP7 depletion reduced oxidative stress, indicated by a 30% reduction in malondialdehyde levels and increases in superoxide dismutase and glutathione peroxidase levels by 25 and 28%, respectively (p < 0.01). Moreover, USP7 knockdown blocked lipid accumulation in aortic tissue cells. Mechanistically, USP7 knockdown inhibited enhancer of Zeste Homolog 2 (EZH2) expression, thereby suppressing AS progression. In conclusion, USP7 depletion alleviated AS progression in ApoE-deficient mice by targeting EZH2 expression. USP7 may serve as a therapeutic target for AS.

Establishment of Mouse Models of Abdominal Aortic Aneurysm.

Abdominal aortic aneurysm (AAA) is a chronic vascular disease that commonly affects elderly individuals but has recently increased in younger populations. As the aneurysm grows, it can cause compression symptoms such as abdominal pain, rupture, and bleeding, which are absent in the early stages. Once an AAA ruptures and causes bleeding, the mortality rate is alarmingly high. Currently, the pathogenesis for AAA is unknown, and therapeutic options are limited, necessitating improvement in treatment efficacy. An essential research method for studying the processes and potential treatment of AAA is establishing animal models using mice. The present study provides a detailed overview of the widely used AAA mouse animal models and their construction strategies, advantages, disadvantages, scope of applications, and prospects.

Targeting Gut Microbiota with Probiotics and Phenolic Compounds in the Treatment of Atherosclerosis: A Comprehensive Review.

Atherosclerosis (AS) is a chronic inflammatory vascular disease. Dysregulated lipid metabolism, oxidative stress, and inflammation are the major mechanisms implicated in the development of AS. In addition, evidence suggests that gut dysbiosis plays an important role in atherogenesis, and modulation of the gut microbiota with probiotics and phenolic compounds has emerged as a promising strategy for preventing and treating AS. It has been shown that probiotics and phenolic compounds can improve atherosclerosis-related parameters by improving lipid profile, oxidative stress, and inflammation. In addition, these compounds may modulate the diversity and composition of the gut microbiota and improve atherosclerosis. The studies evaluated in the present review showed that probiotics and phenolic compounds, when consumed individually, improved atherosclerosis by modulating the gut microbiota in various ways, such as decreasing gut permeability, decreasing TMAO and LPS levels, altering alpha and beta diversity, and increasing fecal bile acid loss. However, no study was found that evaluated the combined use of probiotics and phenolic compounds to improve atherosclerosis. The available literature highlights the synergistic potential between phenolic compounds and probiotics to improve their health-promoting properties and functionalities. This review aims to summarize the available evidence on the individual effects of probiotics and phenolic compounds on AS, while providing insights into the potential benefits of nutraceutical approaches using probiotic strains, quercetin, and resveratrol as potential adjuvant therapies for AS treatment through modulation of the gut microbiota.

Exploring the causal relationship between plasma lipids and varicose veins of lower extremity: A comprehensive two-sample Mendelian randomization study.

Varicose veins of the lower extremities (VVs) is a common chronic vascular disease, with high prevalence rates in some countries; however, their pathogenesis remains unclear. Some studies have identified associations between changes in specific plasma lipid molecules, such as phosphatidylethanolamine (PE), phosphatidylcholine (PC), and sphingomyelin (SM), and the onset of VVs, but due to confounders and reverse causality, the causal relationship remains unclear. Meanwhile, studies on the potential link between other plasma lipids beyond PE, PC, and SM and the risk of VVs in the lower extremities are lacking. This study aimed to explore the potential causal relationship between VVs and plasma lipid levels to provide theoretical insights into the interrelation of plasma lipids and VVs in their occurrence and progression. We conducted a two-sample Mendelian randomization (MR) analysis to assess the potential connection between genetically predicted levels of individual plasma lipids and the risk of developing VVs. We utilized data from a large-scale genome-wide association study involving 7174 Finnish individuals for 179 plasma lipidomes along with VVs genome-wide association study data from 408,455 UK individuals. MR analysis employed methods, such as inverse-variance weighting, weighted median, Bayesian Weighted Mendelian Randomization, and MR-Egger regression. The inverse-variance weighting method was primarily used to assess causality. The validity of the results was demonstrated through sensitivity analysis. In total, 12 lipids were found to have their plasma levels associated with an increased risk of VVs. This includes 3 types of PE, 7 types of PC, and 2 types of phosphatidylinositol. However, no significant causal relationship was found between the plasma levels of 11 types of SM and VVs. These results support the existence of a potential causal relationship between specific types of lipid levels and the risk of VVs, which can provide clues for further studies on biological mechanisms and the exploration of potential therapeutic targets.

Studying the Pulmonary Endothelium in Health and Disease: An Official American Thoracic Society Workshop Report.

Lung endothelium resides at the interface between the circulation and the underlying tissue, where it senses biochemical and mechanical properties of both the blood as it flows through the vascular circuit and the vessel wall. The endothelium performs the bidirectional signaling between the blood and tissue compartments that is necessary to maintain homeostasis while physically separating both, facilitating a tightly regulated exchange of water, solutes, cells, and signals. Disruption in endothelial function contributes to vascular disease, which can manifest in discrete vascular locations along the artery-to-capillary-to-vein axis. Although our understanding of mechanisms that contribute to endothelial cell injury and repair in acute and chronic vascular disease have advanced, pathophysiological mechanisms that underlie site-specific vascular disease remain incompletely understood. In an effort to improve the translatability of mechanistic studies of the endothelium, the American Thoracic Society convened a workshop to optimize rigor, reproducibility, and translation of discovery to advance our understanding of endothelial cell function in health and disease.

Emerging connectivity of programmed cell death pathways and pulmonary vascular remodelling during pulmonary hypertension.

Pulmonary hypertension (PH) is a chronic progressive vascular disease characterized by abnormal pulmonary vascular resistance and pulmonary artery pressure. The major structural alteration during PH is pulmonary vascular remodelling, which is mainly caused by the imbalance between proliferation and apoptosis of pulmonary vascular cells. Previously, it was thought that apoptosis was the only type of programmed cell death (PCD). Soon afterward, other types of PCD have been identified, including autophagy, pyroptosis, ferroptosis and necroptosis. In this review, we summarize the role of the above five forms of PCD in mediating pulmonary vascular remodelling, and discuss their guiding significance for PH treatment. The current review could provide a better understanding of the correlation between PCD and pulmonary vascular remodelling, contributing to identify new PCD-associated drug targets for PH.

NLRP3 inflammasome in atherosclerosis: Mechanisms and targeted therapies.

Atherosclerosis (AS) is the primary pathology behind various cardiovascular diseases and the leading cause of death and disability globally. Recent evidence suggests that AS is a chronic vascular inflammatory disease caused by multiple factors. In this context, the NLRP3 inflammasome, acting as a signal transducer of the immune system, plays a critical role in the onset and progression of AS. The NLRP3 inflammasome is involved in endothelial injury, foam cell formation, and pyroptosis in AS. Therefore, targeting the NLRP3 inflammasome offers a new treatment strategy for AS. This review highlights the latest insights into AS pathogenesis and the pharmacological therapies targeting the NLRP3 inflammasome, focusing on optimal targets for small molecule inhibitors. These insights are valuable for rational drug design and the pharmacological assessment of new targeted NLRP3 inflammasome inhibitors in treating AS.

Targeted delivery of berberine using bionic nanomaterials for Atherosclerosis therapy

Atherosclerosis (AS) is a prevalent chronic vascular inflammatory disease globally, initiated by injury to vascular endothelial cells (VECs). Macrophages play a pivotal role in disease pathogenesis, involving lipid metabolism and inflammation. The application of nanomaterials has been hindered by their rapid clearance by the immune system. Utilizing macrophage cell membranes can mitigate abnormal immune responses and induce a "homing" effect. Here, M2 macrophage cell membranes (M2) were coated onto berberine polylactic-hydroxylase-polylactide (PLGA) nanoparticles (BBR NPs), employing M2 macrophage immune escape, "homing" ability, and membrane coating nanotechnology, and loaded with mannose (Man) to create bionic nanoparticles (BBR NPs@Man/M2). Subsequently, the physical properties of BBR NPs@Man/M2 were characterized. The biocompatibility and biological function of BBR NPs@Man/M2 were assessed in vitro. Finally, the targeting, therapeutic efficacy, and safety of BBR NPs@M2 were investigated in an AS mouse model. The newly developed BBR NPs@Man/M2 exhibited good biocompatibility. Owing to their M2 coating, the nanoparticles effectively targeted macrophages in vitro, inducing a shift from a pro-inflammatory to an anti-inflammatory state. This transition reduced inflammation in endothelial cells and facilitated the repair of damaged endothelial cells. Moreover, M2-coated nanoparticles efficiently targeted and accumulated in atherosclerotic lesions in vivo. Following four weeks of treatment, BBR NPs@Man/M2 significantly delayed AS progression. Furthermore, BBR NPs@Man/M2 demonstrated a good safety profile after long-term administration. In conclusion, BBR NPs@Man/M2 effectively and safely inhibited AS progression. Biomimetic nanoparticles represent a promising approach for the safe and effective delivery of anti-AS drugs.

Age-associated gadolinium leakage into ocular structures in patients with acute traumatic brain injury

BackgroundGadolinium Leakage into Ocular Structures (GLOS) is common following acute cerebrovascular events. The objective of this study was to investigate the occurrence of GLOS in an acute traumatic brain injury (TBI) cohort without acute cerebrovascular injury and to explore associated factors. MethodsEnrolled acute TBI patients had a baseline MRI ≤48 h of injury (TP1) and follow-up MRI ≤72 h after baseline (TP2). Vitreous chamber enhancement and signal intensity ratios (SIRs) were calculated using pre- and post-contrast Fluid Attenuated Inversion Recovery (FLAIR). White matter hyperintensities (WMHs) were assessed using the Fazekas scale. ResultsOf the 128 TBI patients included, median age was 47 years, 70% male, and 66% presented with Glasgow Coma Scale of 15. No GLOS was detected at TP1 but was present in 23% of patients at TP2. GLOS+ patients were older (68 years [56–76] vs 39 years [27–53], p < 0.001), more likely to report falls as injury mechanism (62% vs 36%, p = 0.006), report history of hypertension (41% vs 19%, p = 0.025), and had a higher burden of WMHs (59% vs 14% with a total Fazekas ≥2, p < 0.001). Quantitative SIRs confirmed qualitative assessments: GLOS+ patients had higher SIRs at TP2 (0.43 vs 0.22, p < 0.001). Age (OR 3.28, 95%CI [1.88–5.71], p < 0.001) and prior TBI history (OR 4.99, 95%CI [1.46–17.06], p = 0.010) were independent predictors of GLOS. When age was removed, total Fazekas score (OR 2.53, 95%CI [1.60–4.00], p < 0.001) was an independent predictor of GLOS. ConclusionsGLOS is primarily associated with age and may serve as another imaging marker of chronic vascular disease.

Reactive Oxygen Species‐Triggered Carbon Dots‐Based Biomimetic Nanotheranostic Agents for Atherosclerosis Management

AbstractAtherosclerosis (AS) is a chronic inflammation vascular disease, with its ongoing progression can lead to the onset of cardiovascular diseases. Traditional drug therapy is limited by poor drug delivery, insufficient drug accumulation, and notable toxic side effects. In addition, the failure to receive an early AS diagnosis is primarily responsible for the delayed treatment, which subsequently contributes to the high frequency of life‐threatening cardiovascular events. In this work, a macrophage membranes (MM)‐camouflaged reactive oxygen species (ROS)‐sensitive nanotheranostic platform (LC‐MM) is constructed to improve AS target diagnosis and treatment efficacy. Thanks to the strong antioxidant properties of carbon dots (CDs), CDs as drug carriers for lovastatin aimed to synergistically treat AS by reducing ROS accumulation and suppressing inflammatory responses in vitro and in vivo are employed. The active functions of MM coupled with the ROS‐responsiveness of LC nanoplatform are expected to enhance the efficacy of nanotherapy, particularly to reduce lipid deposition, macrophage infiltration, necrotic core size, collagen content, pro‐inflammatory cytokines, and oxidative stress accumulation. Moreover, the near‐infrared emission properties inherited from CDs facilitated precise fluorescence (FL) imaging for AS plaques. Thus, the biomimetic nanotheranostic agent LC‐MM represented a powerful platform for safe and effective AS management.

Equisetin protects from atherosclerosis in vivo by binding to STAT3 and inhibiting its activity

Atherosclerosis is a chronic inflammatory vascular disease characterized by lipid metabolism disorder and lipid accumulation. Equisetin (EQST) is a hemiterpene compound isolated from fungus of marine sponge origin, which has antibacterial, anti-inflammatory, lipid-lowering, and weight loss effects. Whether EQST has anti-atherosclerotic activity has not been reported. In this study, we revealed that EQST displayed anti- atherosclerosis effects through inhibiting macrophage inflammatory response, lipid uptake and foam cell formation in vitro, and finally ameliorated high-fat diet (HFD)-induced atherosclerosis in AopE-/- mice in vivo. Mechanistically, EQST directly bound to STAT3 with high-affinity by forming hydrophobic bonds at GLN247 and GLN326 residues, as well as hydrogen bonds at ARG325 and THR346 residues. EQST interacted with STAT3 physically, and functionally inhibited the transcription activity of STAT3, thereby regulating atherosclerosis. Therefore, these results supports EQST as a candidate for developing anti-atherosclerosis therapeutic agent.