Vascular Effects Research Articles

Cardiovascular effects and safety of classic psychedelics.

Psychedelics, used for millennia in spiritual and healing practices, have emerged as promising treatments for mental health conditions including depression, post-traumatic stress disorder (PTSD), substance use disorders and anxiety. Despite the therapeutic potential of psychedelics and their increasing use in both medical and nonmedical settings, there is a paucity of data on their cardiovascular safety. Here we review current evidence on the cardiovascular effects and safety of this unique class of therapeutic agents. The cardiovascular effects and associated risks of classic psychedelics are categorized into three areas: electrophysiological effects and arrhythmia risk, structural effects and valvular heart disease risk, and vascular effects including hypertension and ischemia risks. The Review also emphasizes crucial knowledge gaps that require further basic and clinical investigation including studies in individuals with underlying cardiovascular disease, characterization of important drug-drug interactions and studies on the safety of repetitive, long-term (including microdosing) exposure to classic psychedelics.

RBT-1, a "preconditioning" agent, mitigates syndecan-1 shedding in patients undergoing "on pump" cardiac surgery and following experimental AKI.

During systemic stress, syndecan-1 (SDC-1) shedding into plasma results, implying endothelial damage. RBT-1, a "preconditioning" agent, has been shown to mitigate postoperative complications following cardiac surgeries. This study assessed whether RBT-1 preconditioning attenuated SDC-1 shedding in these patients, implying a vascular protective effect. Patients (n, 112) were randomized to receive low-dose RBT-1, high-dose RBT-1, or placebo 24-48 h prior to surgery. Plasma samples were obtained before and 2 days postsurgery and assayed for SDC-1 (ELISA). To gain further insights, male CD-1 mice were subjected to acute renal injuries, and RBT-1's impact on plasma SDC-1 increases, vascular/aortic stress responses (NGAL/KIM-1/IL-6 gene induction), and two vascular cytoprotective pathways (Nrf2; ferritin) were assessed. Baseline plasma SDC-1 levels did not differ between patient groups. The placebo group developed an approximate 50% plasma SDC-1 (ng/mL) increase (p, 0.012). Conversely, no significant SDC-1 increases were seen in the RBT-1 treatment groups. Experimental injury markedly increased plasma SDC-1 concentrations, and these were significantly blunted by RBT-1 preconditioning. RBT-1 also mitigated AKI-induced aortic NGAL/KIM-1/IL-6 mRNA increases, activated aortic Nrf2, and increased vascular ferritin levels. RBT-1 preconditioning diminishes SDC-1 release and upregulates vascular ferritin and Nrf2. Hence, RBT-1 preconditioning can confer select vasoprotective effects.

Abstract TP386: Impaired Bioenergetics in the Aging Cerebral Microvasculature: Effect of Angiotensin-(1-7) or Alamandine

Background: Aging increases risk for the development of vascular cognitive impairment and dementia (VCID). Impaired bioenergetics, mitochondrial oxidative phosphorylation (OxPhos) and glycolysis, in the brain microvascular endothelium induce neurovascular uncoupling, which is one of the underlying mechanisms of VCID. Angiotensin (Ang)-(1-7) and Alamandine (Ala) are vascular protective peptides of renin angiotensin system. Ang-(1-7) is generated by angiotensin-converting enzyme-2 (ACE2) from Ang II, and produces vascular protective effects by acting on Mas receptor (MasR). Ala has been shown to be derived from Ang A by ACE2 or from Ang-(1-7) by an enzyme, which is yet to be characterized, with decarboxylase activity or Mas related G-protein-coupled receptor, member D (MrgD), respectively. This study evaluated the effect of aging on cellular bioenergetics in brain microvasculature (BMV) and tested the potential beneficial effects of Ang-(1-7) or Ala. Methods: BMVs were obtained from Young (Y) and Old (O) mice of age 3 - 4 and 22 – 24 months, respectively, by using ultracentrifugation method. Protein expression of receptors or mitochondrial complexes in BMVs were evaluated by western blotting. Seahorse bioanalyzer was used to determine OxPhos and glycolysis in BMVs. Results: Expression of MasR or MrgD was higher in the O-BMVs compared to the Young ( P < 0.05, n = 4). Expression of mitochondrial respiratory complex proteins, II, IV and V, was lower in the O-BMVs (vs Y-BMVs, P < 0.05, n = 4). MitoStress test revealed that the basal and maximal respiration, and the spare capacity are lower in the O-BMVs compared to the Y-BMVs ( P < 0.05). Ang-(1-7) or Ala (100 nM) increased the basal and maximal respiration, spare capacity and ATP production in the O-BMVs compared to the untreated ( P < 0.05). Glycolysis rate assay (GRA) showed that basal glycolysis and basal proton efflux rate were lower in the O-BMVs ( P < 0.01 vs Y-BMVs) that were increased by Ang-(1-7) or Ala. Conclusion: The study shows that aging is associated with impaired cellular bioenergetics in the brain microvasculature and that the angiotensin peptides, Ang-(1-7) or Ala, restore the bioenergetics therefore have the potential to reverse neurovascular uncoupling in aging.

Sodium valproate reverses aortic hypercontractility in acute myocardial infarction in rabbits.

Sympathetic nervous system (SNS), endothelin 1 (ET-1) and angiotensin II (Ang II) are involved in the pathophysiology of acute myocardial infarction (AMI). Valproic acid (VPA) is under study for the treatment against AMI due to its beneficial cardiac effects. However, the vascular effects of VPA on the activation of the SNS, ET-1 and Ang II after AMI are not fully studied. In our study, we used aorta from New Zealand White rabbits without AMI, with AMI and AMI treated with VPA (500mg/kg/day). AMI was induced by occluding the left circumflex coronary artery for 1h, followed by reperfusion. After 5 weeks, we studied the ex vivo vascular reactivity in organ bath and measured protein expression by Western blot. Our findings indicated that AMI increased vasoconstriction to exogenous and endogenous NE and ET-1, which was reversed by VPA eliciting upregulation of α2-adrenergic and ETB receptors and downregulating ETA receptors. Although no changes in the vascular response to Ang II were observed in AMI or VPA-treated rabbits, an increase in Ang II type 2 receptor expression was found in VPA-treated rabbits. We conclude that VPA could be considered a vascular protector by modulating SNS, ET-1 and Ang II in the aorta, which together with its cardioprotective effect would make it a promising candidate for the treatment of AMI.

A rare vascular manifestation in chronic myeloid leukemia: a case report and literature review of Bier's spot development during nilotinib treatment.

Bier's spots are rare angiospastic macules often associated with physiologic vasoconstriction. This case report describes a 35-year-old man with chronic myeloid leukemia treated with nilotinib who developed Bier's spots, a previously unreported adverse effect of the drug. The patient presented with asymptomatic hypopigmented macules on the hands and legs that appeared during venous stasis and resolved with elevation. This case emphasizes the need to recognize potential vascular side effects of tyrosine kinase inhibitors and highlights Bier's spots as a benign but remarkable manifestation in patients undergoing nilotinib therapy.

Impact of the treatment with TNF inhibitors and JAK Inhibitors on arterial stiffness and lipid parameters in rheumatoid arthritis patients: a cross-sectional study

Abstract Introduction Rheumatoid arthritis (RA) is a chronic inflammatory joint disease associated with an increased cardiovascular risk. Treating disease activity with biologic and synthetic disease-modifying antirheumatic drugs (DMARDs) diminishes cardiovascular risk, but the vascular effects of different biologic and targeted synthetic drugs are poorly understood. Echo-tracking parameters of carotid artery can reveal arterial stiffness as a marker of subclinical atherosclerosis. Methods Patients with RA of at least 6 months of duration, treated with TNF inhibitors or JAK inhibitor - upadacitinib(UPA) and healthy subjects underwent ultrasound examination of carotid artery using the Aloka ProSound Alpha 7. The measurements included pulse-wave velocity (PWVβ), beta-stiffness, augmentation index (AI), arterial compliance (AC), and Ep (Elastic Modulus) and laboratory examination of lipid parameters. Disease activity of RA was measured using Disease activity scores - DAS28-CRP, DAS28-ESR, and Clinical Disease Activity Index (CDAI). Data were analyzed with SPSS v29 and the Kruskal-Wallis test was used to determine statistical differences among the three groups. Results 97 subjects, mean age 55.36±11.84, 83% females. Of them 38 on TNF inhibitors, 36 on UPA, and 23 controls. The three groups were similar in age, BMI, smoking status, and Framingham risk score. Disease activity and disease duration did not differ between the two patients groups. PWV was significantly higher in the UPA group compared to controls but not significantly different from the TNF group. (6.825 vs. 5.8022 vs. 6.468, p=0.034 UPA vs. Control, p=0.59 UPA vs. TNF) (fig.1). AC was lower and Ep was higher in the UPA group compared to controls (0.6511 vs. 0.8678, p=0.032 and132 kPa vs. 92.3, p=0.04 respectively). Total cholesterol levels were higher in the UPA group compared to TNF treated patients and to the control group (fig.2). Conclusion Echo-traching examination of the carotid artery is an easily perfomed, non-invasive and highly informative method of detecting early signs of vascular impairment in patients with RA treated with TNF inhibititors and JAK inhibitor. Treatment with UPA increases the levels of total cholesterol.

CCN5 suppresses injury-induced vascular restenosis by inhibiting smooth muscle cell proliferation and facilitating endothelial repair via thymosin β4 and Cd9 pathway.

Members of the CCN matricellular protein family are crucial in various biological processes. This study aimed to characterize vascular cell-specific effects of CCN5 on neointimal formation and its role in preventing in-stent restenosis (ISR) after percutaneous coronary intervention (PCI). Stent-implanted porcine coronary artery RNA-seq and mouse injury-induced femoral artery neointima single-cell RNA sequencing were performed. Plasma CCN5 levels were measured by enzyme-linked immunosorbent assay. Endothelial cell (EC)- and vascular smooth muscle cell (VSMC)-specific CCN5 loss-of-function and gain-of-function mice were generated. Mass spectrometry and co-immunoprecipitation were conducted to identify CCN5 interacting proteins. Additionally, CCN5 recombinant protein (CCN5rp)-coated stents were deployed to evaluate its anti-ISR effects in a porcine model. Plasma CCN5 levels were significantly reduced and correlated closely with the degree of restenosis in ISR patients. CCN5 expression was significantly decreased in VSMCs of stent-implanted porcine coronary segments and injured mouse femoral arteries, especially in synthetic VSMCs. In contrast, elevated CCN5 expression was observed in regenerating ECs of injured vessels. Endothelial cell- and VSMC-specific CCN5 deletion mice exhibited exacerbation of injury-induced neointimal hyperplasia, while CCN5 gain-of-function alleviated neointimal formation. Mechanistic studies identified thymosin β4 (Tβ4) as a CCN5 interacting protein in ECs and EC-CCN5 promoted injury repair through Tβ4 cleavage product Ac-SDKP. Also, CCN5rp promoted EC repair to suppress neointimal hyperplasia via interaction with Cd9 extracellular domain. Moreover, implantation with CCN5rp-coated stent significantly increased stent strut coverage with ECs, which suppressed neointimal formation and ultimately alleviated ISR. CCN5 exerts a dual protective effect on ISR by inhibiting VSMC proliferation and facilitating EC repair. CCN5rp-coated stent might be promising in the prevention of ISR after PCI.

Cardiovascular Reactivity to Mental Stress and Adverse Cardiovascular Outcomes in Patients With Coronary Artery Disease.

Acute psychological stress may induce physiological changes predisposing individuals to adverse health outcomes through hemodynamic and vascular effects. We studied the association between the aggregated stress-induced changes in hemodynamic and vascular function tests with adverse cardiovascular outcomes in patients with coronary artery disease, after adjusting for sociodemographic and clinical factors. Individuals with stable coronary artery disease from 2 prospective cohort studies were studied. Hemodynamic reactivity, changes in endothelial function, and vasoconstriction during mental stress were evaluated using changes in rate-pressure product, brachial artery flow-mediated vasodilation, and peripheral arterial tonometry, respectively. A cardiovascular reactivity risk score was calculated by allotting 0 to 3 points for each quartile of increasing abnormality for each of the 3 reactivity responses and summing the quartile points from the MIPS (Mental Stress Ischemia Prognosis Study) to yield a cardiovascular reactivity risk score ranging from 0 to 9. The outcome was a composite of cardiovascular death, nonfatal myocardial infarction, and heart failure hospitalizations during follow-up. A total of 629 participants were included. After adjustment for demographic and traditional risk factors, a blunted hemodynamic response, a greater decrease in flow-mediated vasodilation, and a greater degree of peripheral vasoconstriction to mental stress were all independently associated with a higher risk of adverse outcomes in both cohorts. By adding the cardiovascular reactivity risk score, the C-statistic increased significantly by 10% (P<0.001). Among individuals with stable coronary artery disease, a risk score derived from cardiovascular reactivity to mental stress was predictive of adverse cardiovascular outcomes beyond traditional cardiovascular risk factors.

Computational Evaluation of Improved HIPEC Drug Delivery Kinetics via Bevacizumab-Induced Vascular Normalization

Background: Oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) using the original 30 min protocol has shown limited benefits in patients with peritoneal metastasis of colorectal cancer (PMCRC), likely due to the short duration, which limits drug penetration into tumor nodules. Bevacizumab, an antiangiogenic antibody that modifies the tumor microenvironment, may improve drug delivery during HIPEC. This in silico study evaluates the availability of oxaliplatin within tumor nodules when HIPEC is performed after bevacizumab treatment. Methods: Using a computational fluid dynamics (CFD) model of HIPEC, the temperature and oxaliplatin distribution within the rat abdomen were calculated, followed by a model of drug transport within tumor nodules located at various sites in the peritoneum. The vascular normalization effect of the bevacizumab treatment was incorporated by adjusting the biophysical parameters of the tumor nodules. The effective penetration depth values, including the thermal enhancement ratio of cytotoxicity, were then compared between HIPEC alone and HIPEC combined with the bevacizumab treatment. Results: After bevacizumab treatments at doses of 0.5 mg/kg and 5 mg/kg, the oxaliplatin availability increased by up to 20% and 45% when HIPEC was performed during the vascular normalization phase, with the penetration depth increasing by 1.5-fold and 2.3-fold, respectively. Tumors with lower collagen densities and larger vascular pore sizes showed higher oxaliplatin enhancement after the combined treatment. Bevacizumab also enabled a reduction in the oxaliplatin dose (up to half at 5 mg/kg bevacizumab) while maintaining effective drug levels in the tumor nodules, potentially reducing systemic toxicity. Conclusions: These findings suggest that administering oxaliplatin-based HIPEC during bevacizumab-induced vascular normalization could significantly improve drug penetration and enhance treatment efficacy.

A bioactive Hydrogel Patch Accelerates Revascularization in Ischemic Lesions for Tissue Repair

Abstract Background Magnesium ions play crucial roles in maintaining cellular functions. Research has shown that Mg2+ can promote angiogenesis, indicating its potential for treating cardiovascular ischemic diseases. However, conventional intravenous or oral administration of Mg2+ presents several challenges, including the risk of systemic side effects, diminished bioavailability, and a lack of targeted delivery mechanisms. In this study, we designed a Mg2+-releasing adhesive tissue patch (MgAP) that enables the dural release of Mg2+ ions. Methods A novel Mg2+-releasing adhesive patch (MgAP) was developed on the basis of ionic crosslinking. Fourier transform infrared spectroscopy confirmed the chemical structure, whereas rheological analysis demonstrated stable mechanical properties and adaptability to dynamic loads. Sustained Mg2+ release was quantified over 7 days by inductively coupled plasma–mass spectrometry. In a rat acute myocardial infarction model, we performed echocardiography and strain analysis to assess cardiac function and histological staining to evaluate adverse remodeling. We also verified the proangiogenic effect through in vitro tube formation and in vivo immunofluorescence assays. Furthermore, transcriptomics and Western blotting were performed to explore the underlying mechanism. Additional assessments were also carried out in a rat model of lower limb ischemia. Results Compared with intravenous administration of magnesium chloride, MgAP application effectively improved cardiac function and reduced adverse remodeling in the myocardial infarction rat model. The left ventricular ejection fraction increased by 20.3 ± 6.6%, and the cardiac radial strain improved by 27.4 ± 4.1%. The cardiac fibrosis area and cell apoptosis rate decreased by 10.9 ± 1.2% and 32.1 ± 5.5%, respectively. RNA sequencing analysis also highlighted the upregulation of genes related to cardiac electrophysiological properties, structural and functional intercellular connections, and revascularization. The increased gap junction protein expression and restored local blood supply could contribute to the cardiac repair process posttreatment. The proangiogenic effect of MgAP was also observed in the rat limb ischemia model. Conclusions The above results revealed the convincing vascular regeneration effect of an ion therapy-based hydrogel, which enabled the local delivery of Mg2+ to the targeted ischemic tissue, aiding in cardiac and lower limb repair. This study presents a novel strategy and highlights its potential for use across various ischemic conditions.

Not to Be Forgotten, Pulmonary Vascular Effects of Nonmyeloablative Hematopoietic Cell Transplant for Sickle Cell Disease.

Not to Be Forgotten, Pulmonary Vascular Effects of Nonmyeloablative Hematopoietic Cell Transplant for Sickle Cell Disease.

Reply to Holbert and Fraidenburg: Not to Be Forgotten, Pulmonary Vascular Effects of Nonmyeloablative Hematopoietic Cell Transplant for Sickle Cell Disease.

Reply to Holbert and Fraidenburg: Not to Be Forgotten, Pulmonary Vascular Effects of Nonmyeloablative Hematopoietic Cell Transplant for Sickle Cell Disease.

Aspirin and Hemocompatibility After LVAD Implantation in Patients With Atherosclerotic Vascular Disease

The Aspirin and Hemocompatibility Events With a Left Ventricular Assist Device in Advanced Heart Failure (ARIES-HM3) study demonstrated that aspirin may be safely eliminated from the antithrombotic regimen after HeartMate 3 (HM3 [Abbott Cardiovascular]) left ventricular assist device (LVAD) implantation. This prespecified analysis explored whether conditions requiring aspirin (prior percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG], stroke, or peripheral vascular disease [PVD]) would influence outcomes differentially with aspirin avoidance. To analyze aspirin avoidance on hemocompatibility-related adverse events (HRAEs) at 1 year after implant in patients with a history of CABG, PCI, stroke, or PVD. This was an international, multicenter, prospective, double-blind, placebo-controlled, randomized clinical trial including patients implanted with a de novo HM3 LVAD across 51 centers. Data analysis was conducted from April to July 2024. Patients were randomized in a 1:1 ratio to receive aspirin (100 mg per day) or placebo, in addition to a vitamin K antagonist (VKA) targeted to an international normalized ratio of 2 to 3 in both groups. Primary end point (assessed for noninferiority) was a composite of survival free of any nonsurgical (>14 days after implant) HRAEs including stroke, pump thrombosis, bleeding, and arterial peripheral thromboembolism at 12 months. Secondary end points included nonsurgical bleeding, stroke, and pump thrombosis events. Among 589 of 628 patients (mean [SD] age, 57.1 [13.7] years; 456 male [77.4%]) who contributed to the primary end point analysis, a history of PCI, CABG, stroke, or PVD was present in 41% (240 of 589 patients). There was no interaction between the presence of an atherosclerotic vascular condition and effect of aspirin compared with placebo (P for interaction= .23). The preset 10% noninferiority margin was not crossed for the studied subgroup of patients. Thrombotic events were rare, with no differences between aspirin and placebo in patients with and without vascular disease (P for interaction = .77). Aspirin treatment was associated with a higher rate of nonsurgical major bleeding events in the group with prior vascular condition history compared with those without aspirin (rate ratio for placebo compared with aspirin, 0.52; 95% CI, 0.35-0.79). Results of this prespecified analysis of the ARIES-HM3 randomized clinical trial demonstrate that in patients with advanced heart failure who have classical indications for antiplatelet therapy use at the time of LVAD implantation, aspirin avoidance was safe and not associated with increased thrombosis risk. Importantly, elimination of aspirin was associated with no increased thrombosis but a reduction in nonsurgical bleeding events in patients with a history of PCI, CABG, stroke, or PVD. ClinicalTrials.gov Identifier: NCT04069156.

The Molecular Biology of Placental Transport of Calcium to the Human Foetus.

From fertilisation to delivery, calcium must be transported into and within the foetoplacental unit for intracellular signalling. This requires very rapid, precisely located Ca2+ transfers. In addition, from around the eighth week of gestation, increasing amounts of calcium must be routed directly from maternal blood to the foetus for bone mineralisation through a flow-through system, which does not impact the intracellular Ca2+ concentration. These different processes are mediated by numerous membrane-sited Ca2+ channels, transporters, and exchangers. Understanding the mechanisms is essential to direct interventions to optimise foetal development and postnatal bone health and to protect the mother and foetus from pre-eclampsia. Ethical issues limit the availability of human foetal tissue for study. Our insight into the processes of placental Ca2+ handling is advancing rapidly, enabled by developing genetic, analytical, and computer technology. Because of their diverse sources, the reports of new findings are scattered. This review aims to pull the data together and to highlight areas of uncertainty. Areas needing clarification include trafficking, membrane expression, and recycling of channels and transporters in the placental microvilli; placental metabolism of vitamin D in gestational diabetes and pre-eclampsia; and the vascular effects of increased endothelial Orai expression by pregnancy-specific beta-1-glycoproteins PSG1 and PSG9.

Exercised gut microbiota improves vascular and metabolic abnormalities in sedentary diabetic mice through gut‒vascular connection.

Exercise elicits cardiometabolic benefits, reducing the risks of cardiovascular diseases and type 2 diabetes. This study aimed to investigate the vascular and metabolic effects of gut microbiota from exercise-trained donors on sedentary mice with type 2 diabetes and the potential mechanism. Leptin receptor-deficient diabetic (db/db) and nondiabetic (db/m+) mice underwent running treadmill exercise for 8 wk, during which fecal microbiota transplantation (FMT) was parallelly performed from exercise-trained to sedentary diabetic (db/db) mice. Endothelial function, glucose homeostasis, physical performance, and vascular signaling of recipient mice were assessed. Vascular and intestinal stresses, including inflammation, oxidative stress, and endoplasmic reticulum (ER) stress, were investigated. RNA sequencing analysis on mouse aortic and intestinal tissues was performed. Gut microbiota profiles of recipient mice were evaluated by metagenomic sequencing. Chronic exercise improved vascular and metabolic abnormalities in donor mice. Likewise, FMT from exercised donors retarded body weight gain and slightly improved grip strength and rotarod performance in recipient mice. Exercise-associated FMT enhanced endothelial function in different arteries, suppressed vascular and intestinal stresses, and improved glucose homeostasis in recipient mice, with noted microRNA-181b upregulation in aortas and intestines. Altered gut microbiota profiles and gut-derived factors (e.g., short-chain fatty acids and glucagon-like peptide-1) as well as improved intestinal integrity shall contribute to the cardiometabolic benefits, implying a gut‒vascular connection. This proof-of-concept study indicates that exercised microbiota confers cardiometabolic benefits on sedentary db/db mice, extending the beneficial mechanism of exercise through gut‒vascular communication. The findings open up new therapeutic opportunities for cardiometabolic diseases and shed light on the development of exercise mimetics by targeting the gut microbiota.

Consuming Pecans as a Snack Improves Lipids/Lipoproteins and Diet Quality Compared to Usual Diet in Adults at Increased Risk for Cardiometabolic Diseases: A Randomized Controlled Trial.

The vascular and cardiometabolic effects of pecans are relatively under-studied. The aim was to examine how substitution of usual snack foods with 57 g/day of pecans affects vascular health, risk factors for cardiometabolic diseases and diet quality, compared to continuing usual intake in individuals at risk for cardiometabolic diseases. A 12-week single-blinded, parallel, randomized controlled trial was conducted. Adults with ≥1 criterion for metabolic syndrome who were free from cardiovascular disease and type 2 diabetes were included. Participants were provided with 57 g/day of pecans and instructed to replace the snacks usually consumed with the provided pecans. The control group was instructed to continue consuming their usual diet. Flow mediated dilation (FMD; primary outcome), blood pressure, carotid-femoral pulse wave velocity (cf-PWV), lipids/lipoproteins, and glycemic control were measured at baseline and following the intervention. Participants completed three 24-hour recalls at three timepoints (baseline, week 6, and week 12) during the study (9 recalls in total). The Healthy Eating Index-2020 (HEI-2020) was calculated to assess diet quality. In total, 138 participants (Mean±SD;46±13 years, 29.8±3.7 kg/m2) were randomized (69 per group). No between group differences in FMD, cf-PWV or blood pressure were observed. Compared to the usual diet group, pecan intake reduced total cholesterol (-8.1 mg/dL; 95%CI -14.5, -1.7), LDL-C (-7.2 mg/dL; 95%CI -12.3, -2.1), non-HDL-C (-9.5 mg/dL; 95%CI -15.3, -3.7) and triglycerides (-16.4 mg/dL; 95%CI -30.0, -2.9). Weight tended to increase in the pecan group compared with the usual diet group (0.7 kg; 95%CI -0.1, 1.4). The HEI-2020 increased by 9.4 points (95%CI 5.0, 13.7) in the pecan group compared to the usual diet group. Replacing usual snacks with 57 g/day of pecans for 12-weeks improved lipids/lipoproteins and diet quality, but did not affect vascular health in adults at risk for cardiometabolic disease. clinicaltrials.gov NCT05071807.

Hemodynamic Evaluation of Intra-Aortic Dual-Balloon Pump Based on Fluid-Structure Interaction.

The intra-aortic balloon pump (IABP) is a widely-used mechanical circulatory support device that enhances hemodynamics in patients with heart conditions. Although the IABP is a common clinical tool, its effectiveness in enhancing outcomes for patients with acute myocardial infarction and cardiogenic shock remains disputed. This study aimed to assess the effectiveness of intra-aortic dual-balloon pump (IADBP) and its impact on aortic hemodynamics compared with an IABP. Three-dimensional finite element models were constructed for the aorta, IABP, and IADBP, followed by numerical simulation using the fluid-structure coupling (FSI) method. Three simulations were conducted: Heart failure patients without assistive devices (Case A), those with IABP (Case B), and those with IADBP (Case C). The study assessed the IADBP's hemodynamic effects by measuring aortic branch blood flow, left ventricular afterload, aortic wall stress, and wall shear stress. IADBP outperformed IABP in enhancing blood flow to the coronary arteries, upper limbs, and brain vessels (left and right coronary arteries: 0.88 vs. 1.27, 1.27 vs. 1.99 mL/beat; brachiocephalic artery, left common carotid artery, and left subclavian artery: 6.08 vs. 12.39, 2.48 vs. 4.97, 2.31 vs. 5.08 mL/beat). IADBP also demonstrated superior performance in counterpulsation pressure and left ventricular ejection (counterpulsation phase: 97.41 mmHg vs. 110.03 mmHg; ventricular unloading phase: 72.21 mmHg vs. 66.46 mmHg). The use of IADBP elevates stress on the aortic wall and wall shear stress, potentially affecting vascular health. IADBP effectively addresses upper limb and cerebral hypoperfusion issues associated with IABP, demonstrating superior performance in enhancing counterpulsation pressure and left ventricular ejection. Despite potential vascular biomechanical effects, IADBP provide a promising clinical treatment option. Further studies are needed to refine IADBP 's design and evaluate its long-term clinical efficacy.

Retinal and Choroidal Circulation Impairments in Fanconi Anemia.

To evaluate the effects of Fanconi anemia (FA) on retinal and choroidal microvasculature using Optical Coherence Tomography (OCT) and Optical Coherence Tomography Angiography (OCTA). Cohort study with age-matched controls. This study included 11 eyes from 11 patients diagnosed with FA and 12 eyes from 12 age-matched healthy controls. Comprehensive ophthalmic examinations included best-corrected visual acuity (BCVA), intraocular pressure measurements, and OCT/OCTA imaging. Central macular thickness (CMT), subfoveal choroidal thickness (SCT), retinal nerve fiber layer (RNFL) thickness, and choroidal vascularity index (CVI) were measured using OCT. Superficial, deep, and choriocapillaris vessel density, foveal avascular zone (FAZ) parameters, along with radial peripapillary capillary plexus perfusion (RPCPD) and flux index (RPCFI), were assessed using OCTA. Statistical analyses were performed to compare both groups, with adjustments for axial length. Retinal and choroidal microvascular parameters, including CMT, SCT, RNFL thickness, CVI, vessel density, RPCPD, RPCFI and FAZ parameters. There was no significant difference in age or gender distribution between the FA and control groups (p = 0.98, p = 0.80, respectively). The mean age of FA patients was 19.6 ± 11.3 years (range: 6-43), while the mean age of controls was 19.4 ± 10.4 years (range: 8-40). FA patients exhibited significantly reduced SCT (252 ± 72 μm vs. 368 ± 93 μm, p=0.004) compared to controls. Vessel density in the superficial and deep capillary plexuses were significantly lower in FA patients (p=0.042 and p=0.019, respectively). Temporal (45.2 ± 2.3% vs. 48.8 ± 2.8%, p=0.047) and outer (43.6 ± 1.7% vs. 45.8 ± 1.3% p=0.037) RPCPD and temporal (0.43 ± 0.03 vs. 0.47 ± 0.02, p=0.040) and outer (0.41± 0.02 vs. 0.46± 0.02, p=0.010) RPCFI were notably reduced in FA group. CVI was comparable between groups (p=0.857), despite smaller luminal and total areas in FA patients. Fanconi anemia has a profound impact on retinal and choroidal microcirculation, characterized by reduced microvascular densities in the capillary plexi, a lower flux index in the optic nerve head, and thinning of the choroid, even in the absence of visible fundus abnormalities. These findings highlight the significant vascular effects of FA, affecting both the structural integrity and functional capacity of the retina and choroid.

Relaxant Effect of Rosuvastatin in Isolated Rat Aorta with Perivascular Adipose Tissue

Objective: Rosuvastatin displays favorable pleiotropic effects on vascular system to reduce the risk of cardiovascular events besides providing an intensive reduction in LDL-C levels. The role of perivascular adipose tissue (PVAT) in modulating the vasorelaxant effect of rosuvastatin is not evaluated so far. The present study aimed to investigate the vascular relaxant effect of rosuvastatin in rat aortic rings with intact PVAT, as well as to evaluate the possible mechanisms underlying this effect in relation to nitric oxide (NO) and prostaglandin pathways. Methods: Thoracic aorta rings with intact PVAT, isolated from male Wistar rats (n=5), were mounted on an isolated organ bath system. Endothelium-dependent responses to acetylcholine (Ach,10-6-10-4M) were obtained in aortic rings precontracted submaximally with phenylephrine (Phe,10-6-3x105M). The concentration-dependent relaxant effect of rosuvastatin (10-7-10-4M) was examined in the absence and presence of NO inhibitor, L-NOARG (10-4M, 30min.) and cyclooxygenase inhibitor, indomethacin (10-5M, 30min.). Vascular relaxation capacity of aortic rings was checked by the nitrovasodilator, sodium nitroprusside (SNP,10-6 M) at the end of the experiments. Results: Rosuvastatin (10-7-10-4M) produced concentration-dependent relaxations in Phe-precontracted rat aortic rings with intact PVAT. Pretreatment with L-NOARG significantly attenuated the relaxant responses to rosuvastatin in isolated rat aortic rings with intact PVAT. However, pretreatment with indomethacin did not modify the relaxations to rosuvastatin. In the aortic rings, maximal relaxation responses to Ach and SNP were determined to be 75.87±2.68% and 102.54±2.92%, respectively. Conclusions: This study will provide a basis for investigating the interaction between PVAT and statins in vascular homeostasis.

Postprandial Vascular Effects of a High Potassium Meal in Patients with Treated Hypertension.

There is compelling evidence of an inverse association between potassium intake and blood pressure (BP). A potential mechanism for this effect may be dietary potassium-mediated augmentation of endothelium-dependent relaxation. To date, studies have investigated potassium intake supplementation over several weeks in healthy volunteers with variable results on vascular function. There is no assessment of the acute vascular effects of potassium supplementation achieved by the ingestion of potassium-rich food in a hypertensive population. The purpose of this study was to investigate the effect of a high potassium meal on postprandial endothelial function as measured by flow-mediated dilatation (FMD). We performed an investigator-blinded randomized crossover trial in 33 treated hypertensive individuals. Participants consumed both a high (~2400 mg) and low (~543 mg) K+ meal, separated by a one-week washout period. The primary endpoint was endothelial function as assessed by FMD pre-meal and postprandially at 60 and 120 min. Meals were compared at each time point using the Hills-Armitage approach. 33 individuals were included in the study (48% male, mean age 68). In the fasting state (Baseline), and at 60 min postprandial, radial artery FMD was not significantly different between the participants after consumption of either meal (baseline: high K+ 4.2 ± 2% versus Low K+ 2.6 ± 3%, p = 0.93; 60 min: high K+ 3.8 ± 4% versus Low K+ 4.1 ± 3%, p = 0.69). However, at 120 min, FMD tended to be higher in participants after the high K+ meal (5.2 ± 4.1%) than after the low K+ meal (3.9 ± 4.1%) (p = 0.07). There were no differences in participants' radial artery diameter and blood flow between meals. This study does not support our hypothesis that a single high K+ meal improves vascular function in individuals with treated hypertension. This does not contradict the clinical evidence relating greater K+ intake with lower BP, but suggests that mechanistic investigations of increased K+ intake through diet alone and its impact on endothelial function as a mediator to reducing BP are complex and not simply due to single nutrient-mediated improvement in vascular function.