Prevention Of Vascular Disease Research Articles

Adherence to Physical Activity Recommendations Among Stroke Survivors in the United States.

Physical activity is an effective modifiable behavior for preventing recurrent strokes. This study aims to determine the adherence to physical activity recommendations among stroke survivors in the United States. We further compared our findings with the adherence observed among myocardial infarction (MI) survivors and healthy adults, each assessed against distinct physical activity guidelines specific to their respective populations. We utilized data from the 2011 to 2019 Behavioral Risk Factor Surveillance System, a nationally representative survey. To establish benchmarks for stroke survivors, we referenced 3 different physical activity recommendations outlined in 2011, 2014, and 2021 American Heart Association stroke prevention guidelines. Similarly, for MI survivors and healthy adults, we used the 2011 guidelines for secondary prevention of coronary vascular diseases and the 2020 World Health Organization physical activity guidelines, respectively. Adherence to recommendations was determined by the respondents' self-reported intensity, duration, and frequency of physical activity. Multivariate logistic regression compared adherence in stroke survivors, MI survivors, and healthy adults. Among 48 222 stroke survivors in the United States, the overall adherence rates to 2011, 2014, and 2021 physical activity guidelines were 75.4%, 40.2%, and 69.2%. For independently mobile stroke survivors, the adherence rates increased to 78.1%, 42.1%, and 69.9%. Among MI survivors and healthy adults, the adherence rates were 42.7% and 72%. When 2021 recommendations were used as a benchmark, older (aged ≥65 years) stroke survivors were more likely to adhere to recommendations than younger survivors (71.9% versus 62.3%; P<0.0001). After adjusting for sociodemographic factors and comorbidities, non-Hispanic Black survivors were less likely to adhere to recommendations (adjusted odds ratio, 0.81 [95% CI, 0.7-0.94]), whereas older and higher educated stroke survivors were more likely to adhere to recommendations. Geographically, stroke belt and nonrural residents were less likely to adhere to recommendations ([63.5% versus 67.9%; P<0.0001]; [53.8% versus 58.7%; P<0.0001]). Stroke and MI survivors were less likely to adhere to the latest recommendations than healthy adults (adjusted odds ratio, 0.74 [95% CI, 0.69-0.8]; (adjusted odds ratio, 0.24 [95% CI, 0.22-0.26]). A substantial number of stroke survivors do not meet physical activity recommendations. Tailored interventions should be designed for at-risk populations, for example, non-Hispanic Black survivors and lower educated stroke survivors.

Senescence in cardiovascular diseases: Insights into metabolic dysfunction in vascular cells

Senescence is an independent risk factor and plays a critical role in altering vascular structure and functions. Reportedly, senescence accelerates pathological processes and notably increases the risk of cardiovascular diseases, such as atherosclerosis, which are the leading causes of mortality worldwide. Therefore, understanding vascular senescence mechanisms is essential for controlling the increasing incidence and mortality of cardiovascular diseases. This review highlights the progress in research on the various mechanisms underlying the senescence of endothelial cells, smooth muscle cells, and macrophages &amp;ndash; such as stem cell senescence, metabolic dysregulation, mitochondrial autophagy (mitophagy) impairment, and ferroptosis &amp;ndash; and summarizes various antisenescence strategies to target these mechanisms. Key interventions include restoration of the nicotinamide adenine dinucleotide/reduced nicotinamide adenine dinucleotide (NAD+/NADH) ratio and administration of metformin and acarbose to regulate blood glucose levels, which balances the cellular energy and redox. Further, stem cell therapies, rapamycin administration, and melatonin supplementation demonstrate substantial potential. In addition, exercise, dietary modification, and caloric restriction support senescence mitigation. These strategies illustrate the multifaceted nature of senescence and highlight the potential of integrated therapeutic approaches to extend the health span and delay age-related diseases. This review provides a comprehensive summary of age-related metabolic pathways and explores promising antisenescence therapeutic strategies, thereby providing valuable insights into the prevention, diagnosis, and treatment of senescence-related vascular diseases.

Endothelial Dysfunction with Aging: Does Sex Matter?

Oxidative stress and inflammation accompany endothelial dysfunction that results from the excessive or uncontrolled production of reactive oxygen and nitrogen species (RONS) in older adults. This study was designed to assess the usefulness of serum oxi-inflammatory component combinations in vascular disease prediction and prevention with regard to sex. Women (n = 145) and men (n = 50) aged 72.2 ± 7.8 years participated in this project. The females demonstrated the elevated production of hydrogen peroxide (H2O2) and nitric oxide (NO) responsible for intravascular low-density lipoprotein oxidation. NO generation was enhanced in the women, but its bioavailability was reduced, which was expressed by a high 3-nitrotyrosine (3-NitroT) concentration. The relation of NO/3-NitroT (rs = 0.811, p < 0.001) in the women and NO/3-NitroT (rs = -0.611, p < 0.001) in the men showed that sex determines endothelial dysfunction. RONS generation in the women simultaneously promoted endothelial regeneration, as demonstrated by a ~1.5-fold increase in circulating progenitor cells. Inflammation-specific variables, such as the neutrophil-to-lymphocyte ratio, the systemic immune inflammation index, and the neutrophil-to-high-density lipoprotein (HDL) ratio, were reduced in the women and showed their diagnostic utility for clinical prognosis in vascular dysfunction, especially the C-reactive-protein-to-HDL ratio (AUC = 0.980, specificity 94.7%, sensitivity 93.3%, OR = 252, 95% CI 65-967, p < 0.001). This study is the first to have revealed sex-specific changes in the oxi-inflammatory response, which can generate the risk of cardiovascular events at an older age.

Serum peroxiredoxin-4, a biomarker of oxidative stress, associates with new-onset chronic kidney disease: A population-based cohort study

BackgroundChronic Kidney Disease (CKD), is often detected late due to its asymptomatic nature in the early stage of the disease. Overproduction of reactive oxygen species contributes to various pathological processes through oxidative stress (OS), impacting on cellular structures and functions with previous studies suggesting a link between OS and CKD progression. This study investigated the association between serum peroxiredoxin-4 (Prx4), a biomarker of oxidative stress, and the development of CKD in the general population. MethodsThis study featured data from the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) cohort, involving 5341 participants without CKD at baseline who underwent extensive prospective health evaluations. Serum Prx4 levels were quantified using an immunoluminometric assay. The primary outcome was new-onset CKD as defined by the composite of urinary albumin excretion (UAE) > 30 mg/24-h, an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, or both. ResultsBaseline median Prx4 level was 0.65 [interquartile range (IQR): 0.42–1.04] U/L, median eGFR was 98 [IQR: 87–108] mL/min/1.73 m2, and median UAE was 8.1 [IQR: 6.0–12.1] mg/L. During a median follow-up of 10.4 [IQR: 6.3–11.4] years, 867 (16.2 %) patients developed new-onset CKD. Higher Prx4 levels were significantly associated with an increased risk of CKD (hazard ratio (HR) per doubling: 1.29 [95 % confidence interval (CI): 1.21–1.37], p < 0.001), also after adjustment for risk factors including sex, smoking status, systolic blood pressure, high-sensitive C-reactive protein, chronic heart failure, diabetes mellitus and dyslipidemia (HR per doubling: 1.16 [1.06–1.24], p < 0.001). Sensitivity analyses confirmed the robustness of these findings. ConclusionsThis study supports the hypothesis that systemic oxidative stress, reflected by higher serum Prx4 levels, is significantly associated with the risk of developing CKD in the general population. These findings suggest that Prx4 could be a valuable biomarker for early risk stratification and prevention strategies in CKD management.

Recent Advances in Nanozyme-Based Sensing Technology for Antioxidant Detection.

Antioxidants are substances that have the ability to resist or delay oxidative damage. Antioxidants can be used not only for the diagnosis and prevention of vascular diseases, but also for food preservation and industrial production. However, due to the excessive use of antioxidants, it can cause environmental pollution and endanger human health. It can be seen that the development of antioxidant detection technology is important for environment/health maintenance. It is found that traditional detection methods, including high performance liquid chromatography, gas chromatography, etc., have shortcomings such as cumbersome operation and high cost. In contrast, the nanozyme-based detection method features advantages of low cost, simple operation, and rapidity, which has been widely used in the detection of various substances such as glucose and antioxidants. This article focuses on the latest research progress of nanozymes for antioxidant detection. Nanozymes for antioxidant detection are classified according to enzyme-like types. Different types of nanozyme-based sensing strategies and detection devices are summarized. Based on the summary and analysis, one can find that the development of commercial nanozyme-based devices for the practical detection of antioxidants is still challenging. Some emerging technologies (such as artificial intelligence) should be fully utilized to improve the detection sensitivity and accuracy. This article aims to emphasize the application prospects of nanozymes in antioxidant detection and to provide new ideas and inspiration for the development of detection methods.

Positive impact of nutrition in the prevention of peripheral vascular disease and severe acute respiratory syndrome coronavirus 2: review.

Recent research has shown that there is a link between the trend of cardiovascular disease (CVD), chronic symptoms of SARS-CoV-2 (COVID-19), and medical nutrition therapy. Making positive changes to an individual's lifestyle can help to reduce the symptoms that follow exposure to CVD and COVID-19. Sustainable nutrition and lifestyle changes can positively impact an individual's health. Studies have considered the risk factors associated with the disease, medical history, the link between nutrition and peripheral vascular disease (PVD), symptom management, and the interrelationship between nutrition, COVID-19, and PVD. One study has demonstrated that Western Dietary intake can boost the innate immune system while suppressing humoral response, causing chronic inflammation and poor host defense against viruses. However, further investigation is needed to confirm. Patients with PVD and COVID-19 have experienced a reduction in side effects when prescribed a regimen of medical nutrition therapy, heart-healthy diets, and adequate physical activity before and after symptoms of both diseases appear. This approach has proven to be a protective factor during the combination of both illnesses. Our findings indicate that balanced diet and lifestyle are essential in supporting an optimal immune system that can reduce the risk of virus load in individuals at risk of infection and symptoms from COVID-19 and PVD.

Anthocyanins in Vascular Health and Disease: Mechanisms of Action and Therapeutic Potential.

Unhealthy lifestyles have placed a significant burden on individuals' cardiovascular health. Anthocyanins are water-soluble flavonoid pigments found in a wide array of common foods and fruits. Anthocyanins have the potential to contribute to the prevention and treatment of cardiovascular disease by improving lipid profiles and vascular function, reducing blood glucose levels and blood pressure, and inhibiting inflammation. These actions have been demonstrated in numerous clinical and preclinical studies. At the cellular and molecular level, anthocyanins and their metabolites could protect endothelial cells from senescence, apoptosis, and inflammation by activating the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthases, silent information regulator 1 (SIRT1), or nuclear factor erythroid2-related factor 2 pathways and inhibiting the nuclear factor kappa B, Bax, or P38 mitogen-activated protein kinase pathways. Furthermore, anthocyanins prevent vascular smooth muscle cell from platelet-derived growth factor -induced or tumor necrosis factor-α-induced proliferation and migration by inhibiting the focal adhesion kinase and extracellular regulated protein kinases signaling pathways. Anthocyanins could also attenuate vascular inflammation by reducing the formation of oxidized lipids, preventing leukocyte adhesion and infiltration of the vessel wall, and macrophage phagocytosis of deposited lipids through reducing the expression of cluster of differentiation 36 and increasing the expression of ATP-binding cassette subfamily A member 1 and ATP-binding cassette subfamily G member 1. At the same time, anthocyanins could lower the risk of thrombosis by inhibiting platelet activation and aggregation through down-regulating P-selectin, transforming growth factor-1, and CD40L. Thus, the development of anthocyanin-based supplements or derivative drugs could provide new therapeutic approaches to the prevention and treatment of vascular diseases.

Spicy food consumption and risk of vascular disease: Evidence from a large-scale Chinese prospective cohort of 0.5 million people.

Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association. This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results. During a median follow-up time of 12.1years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1-2days/week (hazard ratio [HR]=0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P<0.001), 3-5days/week (HR = 0.96, 95% CI = [0.94, 0.99], P=0.003), and 6-7days/week (HR = 0.97, 95% CI = [0.95, 0.99], P=0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week (Ptrend<0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD (Ptrend=0.011) and MCEs (Ptrend=0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD (Pinteraction=0.037). Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.

Buyang Huanwu Decoction suppresses ischemic stroke by suppressing glycolysis and cell apoptosis in rat brain microvascular endothelial cells

BackgroundBuyang Huanwu Decoction (BHD) is widely used in Chinese clinical practice for the treatment and prevention of ischemic cerebral vascular diseases. This study was designed to investigate the effects of BHD on ischemic stroke (IS) and its underlying mechanism. MethodsThe middle cerebral artery occlusion (MCAO) rat model and oxygen-glucose deprivation and reoxygenation (OGD/R) rat brain microvascular endothelial cell (RBMVEC) models were established. Brain infarction size and neurological score were calculated following MCAO surgery. Evans blue was used to measure blood brain barrier (BBB) permeability. Cell counting kit-8 (CCK-8) and TUNEL assays were performed to evaluate the cell viability and apoptosis of RBMVECs. Dual-luciferase reporter assay was used to analyze the transcriptional activities of apoptosis-related genes. ResultsResults showed that higher infarction volume, neurological scores, and BBB permeability in the MCAO group rats were reduced after BHD treatment. Drug serum (DS) treatment had no impact on the normal RBMVECs’ cell viability and cell apoptosis. Besides, DS treatment decreased the lactate production, glucose uptake, and extracellular acidification rate in normal and OGD/R-induced RBMVECs. DS treatment downregulated the protein levels of pan-lysine lactylation (kla), histone H3 lysine 18 lactylation (H3K18la), and the transcriptional of apoptotic protease activating factor-1 (Apaf-1) in OGD/R-treated RBMVECs. In addition, Apaf-1 overexpression decreased cell viability and increased apoptosis and glycolysis activity of OGD/R-treated RBMVECs. ConclusionIn summary, BHD inhibited glycolysis and apoptosis via suppressing the pan-kla and H3K18la protein levels and the Apaf-1 transcriptional activity, thus restraining the progression of IS.

Association of baseline and longitudinal changes in insulin-like growth factor-binding protein-7 with the risk of incident heart failure: Data from the PREVEND study.

Senescence is a major risk factor for heart failure (HF), and insulin-like growth factor-binding protein-7 (IGFBP7) has been identified as an important senescence-inducing factor. The aim of this study was to examine the value of baseline and repeat IGFBP7 measurements in predicting future HF among community-dwelling Dutch adults from the Prevention of Renal and Vascular End-stage Disease (PREVEND) study. Individuals without prevalent HF who attended PREVEND visits 2 and 4 median of 5.1 years apart (25th-75th percentile, 4.9-5.2) with measurements of IGFBP7 were included. We used Cox proportional hazards models to investigate the association between IGFBP7 and HF incidence. A total of 6125 participants attending visit 2 (mean ± standard deviation [SD] age 53.1 ± 12.2 years; 3151 [51.4%] men) were followed for a median of 8.4 (7.8-8.9) years, and 194 participants (3.2%) developed incident HF. Median baseline IGFBP7 concentration was 87.0 (75.1-97.3) ng/ml, and baseline IGFBP7 levels were significantly associated with risk for incident HF (HF risk factors adjusted hazard ratio [HR] per 1 SD change in log-transformed IGFBP7: 1.22, 95% confidence interval [CI] 1.03-1.46). Baseline IGFBP7 was also significantly associated with incident HF in individuals with N-terminal pro-B-type natriuretic peptide <125 ng/L. Among 3879 participants attending both visits 2 and 4 (mean ± SD age 57.5 ± 11.3 years; 1952 [50.3%] men), 93 individuals developed HF (after visit 4) during a median follow-up of 3.2 (2.8-3.9) years. Median increase in IGFBP7 concentration between visits was 0.68 (-7.09 to 8.36) ng/ml, and changes in IGFBP7 levels were significantly associated with risk for incident HF (HF risk factors adjusted HR per 1 SD change in log-transformed IGFBP7: 1.68, 95% CI 1.19-2.36). Both baseline as well as repeat IGFBP7 measurements provide information about the risk of developing HF.

The Influence of Various Types of Physical Activity on Blood Pressure. A Literature Review

Blood pressure is a key indicator of cardiovascular health, playing a significant role in the diagnosis, prevention, and treatment of heart and vascular diseases. In recent years, interest in the influence of physical activity on blood pressure has increased among researchers and health-conscious individuals. Among the studies presented, researchers examined the effects of various types of physical activity on blood pressure in individuals with hypertension and the level of hypertension control, as well as other components affecting the overall health of patients, such as blood lipid levels, arterial pressure variability over 24 hours, and BMI. The conclusions of the presented studies seemed to be consistent regarding the positive impact of engaging in physical activity on blood pressure and thus the better well-being of patients.

Guidelines for the diagnosis and treatment of chronic thromboembolic pulmonary hypertension (2024 edition)

Chronic thromboembolic pulmonary hypertension (CTEPH) is classified as group 4 pulmonary hypertension, characterized by pulmonary arterial thrombotic occlusion leading to vascular stenosis or obstruction, progressive elevation of pulmonary vascular resistance and pulmonary arterial pressure, ultimately leading to right heart failure and even death. Recent years have seen rapid progress in the diagnostic and therapeutic in CTEPH field. More and more patients with CTEPH have been accurately diagnosed and assessed in time. Nevertheless, there is still a lot of work to do in the popularization of CTEPH diagnostic and therapeutic technique and the building of CTEPH expert center. To better guide clinical practice in our country, Pulmonary Embolism & Pulmonary Vascular Diseases Group of the Chinese Thoracic Society, Pulmonary Embolism & Pulmonary Vascular Disease Working Group of Chinese Association of Chest Physicians, National Cooperation Group on Prevention & Treatment of Pulmonary Embolism & Pulmonary Vascular Disease, National Expert Panel on the Development of a Standardized Framework for Pulmonary Arterial Hypertension, convened multidisciplinary experts for deliberation and Delphi expert consensus to develop the "Guidelines for the Diagnosis and Treatment of Chronic Thromboembolic Pulmonary Hypertension (2024 edition) ". These guidelines systematically evaluate domestic and international evidence-based medical research on CTEPH and propose recommendations tailored to clinical practice in our country. The key areas covered include definitions, epidemiology, pathogenesis, diagnosis and assessment, treatment, and management, with the aim of further standardizing the clinical diagnosis and treatment of CTEPH in our country.

CCL11 released by GSDMD-mediated macrophage pyroptosis regulates angiogenesis after hindlimb ischemia

Peripheral vascular disease (PVD) is an emerging public health burden with a high rate of disability and mortality. Gasdermin D (GSDMD) has been reported to exert pyroptosis and play a critical role in the pathophysiology of many cardiovascular diseases. We ought to determine the role of GSDMD in the regulation of perfusion recovery after hindlimb ischemia (HLI). Our study revealed that GSDMD-mediated pyroptosis occurred in HLI. GSDMD deletion aggravated perfusion recovery and angiogenesis in vitro and in vivo. However, how GSDMD regulates angiogenesis after ischemic injury remains unclear. We then found that GSDMD-mediated pyroptosis exerted the angiogenic capacity in macrophages rather than endothelial cells after HLI. GSDMD deletion led to a lower level of CCL11 in mice serum. GSDMD knockdown in macrophages downregulated the expression and decreased the releasing level of CCL11. Furthermore, recombinant CCL11 improved endothelial functions and angiogenesis, which was attenuated by CCL11 antibody. Taken together, these results demonstrate that GSDMD promotes angiogenesis by releasing CCL11, thereby improving blood flow perfusion recovery after hindlimb ischemic injury. Therefore, CCL11 may be a novel target for prevention and treatment of vascular ischemic diseases.

Serum Calcification Propensity Is Increased in Myocardial Infarction and Hints at a Pathophysiological Role Independent of Classical Cardiovascular Risk Factors.

Vascular calcification is associated with increased mortality in patients with cardiovascular disease. Secondary calciprotein particles are believed to play a causal role in the pathophysiology of vascular calcification. The maturation time (T50) of calciprotein particles provides a measure of serum calcification propensity. We compared T50 between patients with ST-segment-elevated myocardial infarction and control subjects and studied the association of T50 with cardiovascular risk factors and outcome. T50 was measured by nephelometry in 347 patients from the GIPS-III trial (Metabolic Modulation With Metformin to Reduce Heart Failure After Acute Myocardial Infarction: Glycometabolic Intervention as Adjunct to Primary Coronary Intervention in ST Elevation Myocardial Infarction: a Randomized Controlled Trial) and in 254 matched general population controls from PREVEND (Prevention of Renal and Vascular End-Stage Disease). We also assessed the association between T50 and left ventricular ejection fraction, as well as infarct size, the incidence of ischemia-driven reintervention during 5 years of follow-up, and serum nitrite as a marker of endothelial dysfunction. Patients with ST-segment-elevated myocardial infarction had a significantly lower T50 (ie, higher serum calcification propensity) compared with controls (T50: 289±63 versus 338±56 minutes; P<0.001). In patients with ST-segment-elevated myocardial infarction, lower T50 was associated with female sex, lower systolic blood pressure, lower total cholesterol, lower LDL (low-density lipoprotein) cholesterol, lower triglycerides, and higher HDL (high-density lipoprotein) cholesterol but not with circulating nitrite or nitrate. Ischemia-driven reintervention was associated with higher LDL (P=0.03) and had a significant interaction term for T50 and sex (P=0.005), indicating a correlation between ischemia-driven reintervention and T50 above the median in men and below the median in women, between 150 days and 5 years of follow-up. Serum calcification propensity is increased in patients with ST-segment-elevated myocardial infarction compared with the general population, and its contribution is more pronounced in women than in men. Its lack of/inverse association with nitrite and blood pressure confirms T50 to be orthogonal to traditional cardiovascular disease risk factors. Lower T50 was associated with a more favorable serum lipid profile, suggesting the involvement of divergent pathways of calcification stress and lipid stress in the pathophysiology of myocardial infarction.

Myeloid Cell mPGES-1 Deletion Attenuates Calcium Phosphate-induced Abdominal Aortic Aneurysm in Male Mice.

Microsomal PGE2 synthase (mPGES)-1 is the key enzyme responsible for synthesizing inflammatory prostaglandin E2 (PGE2). Our previous studies have shown that deletion mPGES-1 in myeloid cells hinders atherogenesis, suppresses vascular proliferative response to injury and enhances survival after myocardial infarction.Here we aimed to further explore the influence of myeloid cell mPGES-1 deletion in abdominal aortic aneurysm (AAA) formation. The AAA was triggered by applying 0.5M calcium phosphate (CaPO4) to the infrarenal aorta of both myeloid mPGES-1 knockout (Mac-mPGES-1-KO) and their littermate control Mac-mPGES-1-WT mice. AAA induction was assessed by calculating the expansion of the infrarenal aortic diameter 4weeks after CaPO4 application. The maximum diameters of the aortas were measured by morphometry and the mean maximal diameters were calculated. Paraffin sections of the infrarenal aortas were examined for morphological analysis and immunohistochemical staining. The results showed that myeloid cell mPGES-1 deletion significantly mitigated AAA formation, including reducing expansion of the infrarenal aorta, preventing elastic lamellar degradation, and decreasing aortic calcium deposition. Immunohistochemical staining further indicated that macrophage infiltration and matrix metalloproteinase 2 (MMP2) expression was attenuated in the Mac-mPGES-1-KO aortas. Consistently, in vitro experiments showed that expression of pro-inflammatory cytokines and MMPs was significantly reduced when mPGES-1 was lacking in the primary cultured peritoneal macrophages. These data altogether demonstrated that deletion of mPGES-1 in myeloid cells may attenuate AAA formation and targeting myeloid cell mPGES-1 could potentially offer an effective strategy for the treatment and prevention of vascular inflammatory diseases.

Peptide functionalized biomimetic gene complexes enhance specificity for vascular endothelial regeneration

Gene delivery presents great potential in endothelium regeneration and prevention of vascular diseases, but its outcome is inevitably limited by high shear stress and instable microenvironment. Highly efficient nanosystems may alleviate the problem with strong dual-specificity for diseased site and targeted cells. Hence, biomimetic coatings incorporating EC-targeting peptides were constructed by platelets and endothelial cells (ECs) for surface modification. A series of biomimetic gene complexes were fabricated by the biomimetic coatings to deliver pcDNA3.1-VEGF165 plasmid (pVEGF) for rapid recovery of endothelium. The gene complexes possessed good biocompatibility with macrophages, stability with serum and showed no evident cytotoxicity for ECs even at very high concentrations. Furthermore, the peptide modified gene complexes achieved selective internalization in ECs and significant accumulation in endothelium-injured site, especially the REDV-modified and EC-derived gene complexes. They substantially enhanced VEGF expression at mRNA and protein levels, thereby enabling a wound to heal completely within 24 h according to wound healing assay. In an artery endothelium-injured mouse model, the REDV-modified and EC-derived gene complexes presented efficient re-endothelialization with the help of enhanced specificity. The biomimetic gene complexes offer an efficient dual-targeting strategy for rapid recovery of endothelium, and hold potential in vascular tissue regeneration.

Purinergic regulation of pulmonary vascular tone.

Purinergic signaling is a crucial determinant in the regulation of pulmonary vascular physiology and presents a promising avenue for addressing lung diseases. This intricate signaling system encompasses two primary receptor classes: P1 and P2 receptors. P1 receptors selectively bind adenosine, while P2 receptors exhibit an affinity for ATP, ADP, UTP, and UDP. Functionally, P1 receptors are associated with vasodilation, while P2 receptors mediate vasoconstriction, particularly in basally relaxed vessels, through modulation of intracellular Ca2+ levels. The P2X subtype receptors facilitate extracellular Ca2+ influx, while the P2Y subtype receptors are linked to endoplasmic reticulum Ca2+ release. Notably, the primary receptor responsible for ATP-induced vasoconstriction is P2X1, with α,β-meATP and UDP being identified as potent vasoconstrictor agonists. Interestingly, ATP has been shown to induce endothelium-dependent vasodilation in pre-constricted vessels, associated with nitric oxide (NO) release. In the context of P1 receptors, adenosine stimulation of pulmonary vessels has been unequivocally demonstrated to induce vasodilation, with a clear dependency on the A2B receptor, as evidenced in studies involving guinea pigs and rats. Importantly, evidence strongly suggests that this vasodilation occurs independently of endothelium-mediated mechanisms. Furthermore, studies have revealed variations in the expression of purinergic receptors across different vessel sizes, with reports indicating notably higher expression of P2Y1, P2Y2, and P2Y4 receptors in small pulmonary arteries. While the existing evidence in this area is still emerging, it underscores the urgent need for a comprehensive examination of the specific characteristics of purinergic signaling in the regulation of pulmonary vascular tone, particularly focusing on the disparities observed across different intrapulmonary vessel sizes. Consequently, this review aims to meticulously explore the current evidence regarding the role of purinergic signaling in pulmonary vascular tone regulation, with a specific emphasis on the variations observed in intrapulmonary vessel sizes. This endeavor is critical, as purinergic signaling holds substantial promise in the modulation of vascular tone and in the proactive prevention and treatment of pulmonary vascular diseases.

Associations of between- and within-day patterns of physical activity accumulation with arterial stiffness and indices of microvascular health-Evidence from The Maastricht study.

While physical activity (PA) is understood to promote vascular health, little is known about whether the daily and weekly patterns of PA accumulation associate with vascular health. Accelerometer-derived (activPAL3) 6- or 7-day stepping was analyzed for 6430 participants in The Maastricht Study (50.4% women; 22.4% Type 2 diabetes mellitus (T2DM)). Multivariable regression models examined associations between stepping metrics (average step count, and time spent slower and faster paced stepping) with arterial stiffness (measured as carotid-femoral pulse wave velocity (cfPWV)), and several indices of microvascular health (heat-induced skin hyperemia, retinal vessel reactivity and diameter), adjusting for confounders and moderators. PA pattern metrics were added to the regression models to identify associations with vascular health beyond that of stepping metrics. Analyses were stratified by T2DM status if an interaction effect was present. Average step count and time spent faster paced stepping was associated with better vascular health, and the association was stronger in those with compared to those without T2DM. In fully adjusted models a higher step count inter-daily stability was associated with a higher (worse) cfPWV in those without T2DM (std β = 0.04, p = 0.007) and retinal venular diameter in the whole cohort (std β = 0.07, p = 0.002). A higher within-day variability in faster paced stepping was associated with a lower (worse) heat-induced skin hyperemia in those with T2DM (std β = -0.31, p = 0.008). Above and beyond PA volume, the daily and weekly patterns in which PA was accumulated were additionally associated with improved macro- and microvascular health, which may have implications for the prevention of vascular disease.

Iron status in Dutch and Finnish blood donor and general populations: A cross-cohort comparison study.

Blood donors are at risk of developing iron deficiency (ID) (ferritin <15 μg/L, World Health Organization definition). Blood services implement different strategies to mitigate this risk. Although in Finland risk group-based iron supplementation is in place, no iron supplementation is provided in the Netherlands. We aim to describe differences in ferritin levels and ID prevalence in donor and general populations in these countries. Six cohorts, stratified based on sex, and for women age, in the Netherlands and Finland were used to evaluate differences in ferritin levels and ID between donor populations (Donor InSight-III and FinDonor 10,000) and general populations (Prevention of Renal and Vascular End-Stage Disease [PREVEND], FinRisk 1997 and Health 2000) and newly registered Dutch donors. Multivariable logistic regression was used to quantify associations of various explanatory factors with ID. In total, 13,443 Dutch and 13,933 Finnish subjects were included. Donors, except for women aged ≤50 years old in Finland, had lower median ferritin levels compared with the general population and new donors. Dutch regular blood donors had higher or similar prevalence of ID as compared with the Dutch general population, including new donors. In contrast, Finnish donors showed similar prevalence of ID compared with the general population, except for a markedly lower prevalence in ≤50-year-old women who routinely receive iron supplements when donating. Iron status in blood donors differs from that in the general population. The Finnish blood service donor management policy, for example, iron supplementation for risk groups, seemingly protects young female blood donors from developing ID.

Enhanced chronic inflammation and increased branched chain amino acids in adrenal disorders: a cross-sectional study.

Patients with adrenal hormone excess demonstrate increased cardiovascular risk and mortality. We aimed to determine the impact of adrenal disorders on the inflammation marker GlycA, total branched-chain amino acids (BCAA), ketone bodies and the gut microbiome-derived metabolites trimethylamine N-oxide (TMAO) and betaine. We conducted a single-center cross-sectional study of patients with nonfunctioning adenomas (NFA), mild autonomous cortisol secretion (MACS), primary aldosteronism (PA), Cushing syndrome (CS), pheochromocytoma/paragangliomas (PPGL), other benign or malignant adrenal masses, and adrenocortical carcinoma (ACC) between January 2015 and July 2022 (n=802). Referent subjects included participants of the PREVEND (Prevention of Renal and Vascular End-stage Disease) study (n=5241). GlycA, BCAA, ketone bodies, TMAO, and betaine were measured using nuclear magnetic resonance spectroscopy. Multivariable logistic analyses were adjusted for age, sex, BMI, smoking, hypertension, diabetes mellitus and statin therapy. In age-and sex-adjusted comparison to referent subjects, increased GlycA was noted in all patient categories, increased BCAA in NFA, MACS, CS, PA and ACC, increased TMAO in patients with other malignant adrenal masses, increased betaine in NFA and MACS, and increased ketone bodies in NFA, CS and ACC. Essentially similar findings were observed in fully adjusted analysis and after exclusion of subjects with diabetes and cardiovascular disease. Patients with functioning and non-functioning adrenal masses demonstrated increased GlycA and BCAA, biomarkers associated with adverse cardiometabolic disorders and mortality. Patients with NFA demonstrated an adverse metabolic profile similar to patients with MACS and CS.