Vascular System Research Articles

X-ray fluorescence mapping of brain tissue reveals the profound extent of trace element dysregulation in stroke pathophysiology.

The brain is a privileged organ with regards to its trace element composition and maintains a robust barrier system to sequester this specialized environment from the rest of the body and the vascular system. Stroke is caused by loss of adequate blood flow to a region of the brain. Without adequate blood flow ischemic changes begin almost immediately, triggering an ischemic cascade, characterized by ion dysregulation, loss of function, oxidative damage, cellular degradation, and break down of the barrier that helps maintain this environment. Ion dysregulation is a hallmark of stroke pathophysiology and we observe that most elements in the brain are dysregulated after stroke. X-ray fluorescence-based detection of physiological changes in the neurometallome after stroke reveals profound ion dysregulation within the lesion and surrounding tissue. Not only are most elements significantly dysregulated after stroke, but the level of dysregulation cannot be predicted from a cell-level description of dysregulation. X-ray fluorescence imaging reveals that the stroke lesion retains<25% of essential K+ after stroke, but this element is not concomitantly elevated elsewhere in the organ. Moreover, elements like Na+, Ca2+, and Cl- are vastly elevated above levels available in normal brain tissue (>400%, >200%, and>150%, respectively). We hypothesize that weakening of the blood-brain-barrier after stroke allows elements to freely diffuse down their concentration gradient so that the stroke lesion is in equilibrium with blood (and the compartments containing brain interstitial fluid and cerebrospinal fluid). The changes observed for the neurometallome likely has consequences for the potential to rescue infarcted tissue, but also presents specific targets for treatment.

Feeding postures as indicators of mutable collagenous tissue in extinct echinoderms.

Echinoderms are a diverse phylum with a rich fossil record. The five extant classes of echinoderms are characterised by a pentameral (or pseudo-pentameral) symmetry, a water vascular system, a mesodermal skeleton of calcite stereom, and Mutable Collagenous Tissue (MCT), a unique type of connective tissue. Difficulties in tracing the geologic history of these traits complicates phylogenetic analyses of echinoderms. We present evidence herein of MCT in an extinct class of echinoderms, the Blastoidea. Blastoids have composite hair-like structures, brachioles, which formed a feeding filtration fan. Rare specimens from the Devonian of Germany demonstrate the presence of MCT by preserving brachioles as long rigid structures making a feeding fan with MCT in a rigid state. Specimens show brachioles in different configurations in the same specimen, which may indicate nervous control of MCT in individual brachioles. Other specimens appear to indicate the transition of MCT from a rigid to a compliant state as rigid brachioles begin to curve. Still other specimens show a majority of brachioles as limp hair-like structures swept by currents while a minority of brachioles remain rigid. These remarkable specimens could capture MCT transitioning from its rigid to compliant states in individual specimens indicating rapid burial and preservation.

The relationship between dietary vitamin B1 intake and severe abdominal aortic calcification among the general population in the United States

BackgroundVitamin B1 deficiency is closely associated with vascular system damage, but the relationship between dietary vitamin B1 intake and abdominal aortic calcification (AAC) remains unclear and warrants further investigation.Methods2,640 participants from the National Health and Nutrition Examination Survey (NHANES) 2013–2014 were included in the study. Severe AAC was defined as Kauppila score &amp;gt;5. Multivariable logistic regression analysis and restricted cubic splines (RCS) were used to examine the relationship between dietary vitamin B1 and severe AAC.ResultsThe increase in dietary intake of vitamin B1 is significantly correlated with a decrease in the risk of severe AAC (OR: 0.601, 95% CI: 0.406, 0.892). Compared to the first quartile of dietary vitamin B1 intake, the fourth quartile had a significantly reduced risk of severe AAC (OR: 0.358, 95% CI: 0.172, 0.744). RCS indicated a decreasing trend in the risk of severe AAC with increasing dietary vitamin B1 intake.ConclusionOur research findings indicate that the increase in dietary intake of vitamin B1 is significantly associated with a decrease in the risk of severe AAC. Thus, increasing dietary vitamin B1 intake appropriately may reduce the risk of severe AAC.

BN SO31 - Pedicle First; a Paved Laparoscopic Approach for Huge Splenomegaly

Abstract Background Since its introduction for the first time by Delaitre et al1 in 1991, laparoscopic splenectomy (LS) has become the minimal invasive approach of choice for the management of the hematological splenic disorders2. Many agreed benefits have been achieved with this approach regarding the hospital stay, blood loss, duration of recovery, aesthetic results and quality of life; however, massive spleens remain a real technical challenge in front of achieving those benefits. The complex and non-typical variable configurations of the vascular system for the pancreatic body and tail which come from the splenic artery represents another faced point of anatomical complications3. Method From March 2020 to February 2024, a prospective study has included 30 patients presented with benign hematological disorders and massive splenomegaly (more than 20 cm longitudinal axis) who underwent laparoscopic splenectomy in our institution. Detailed data regarding their demographics, splenic size, operative time, blood loss, conversion rate, postoperative serum amylase and hospital stay were collected. Standardized anterior approach operative steps were adopted by the same surgeon for all patients with early control of the arterial system of the splenic circulation before mobilization (short gastric vessels and splenic artery 2 to 4 cm away from hilum). Results Thirty patients presented with huge splenomegaly have underwent laparoscopic splenectomy with a conversion rate of 6.6% (2 patients due to extensive perisplenic adhesions). The mean longitudinal splenic dimension was 24 ± 1.5 cm (range from 20 to 27 cm), mean operative time was 110 ± 16 minutes, mean operative blood loss was 160 ± 20 ml, mean hospital stay was 4 ± 1.5 days, postoperative rate of hyperamylasemia in 20% (asymptomatic 6 patients with no operative evidence of pancreatic injury), respiratory complications in 16.6 % (5 patients), and reactive thrombocytosis in 6.6% (2 patients). Conclusion Early laparoscopic control of the arterial system away from the splenic hilum can enable us to lessen the conversion rate for massive splenomegaly patients and achieve successfully the benefits of laparoscopy for those patients on the expense of the elevated postoperative hyperamylasemia rate.

Mouse Models Enable the Functional Investigation of Tertiary Lymphoid Structures in Cancer.

Tertiary lymphoid structures (TLSs) are organized lymphoid aggregates that form within nonlymphoid tissue, including tumors, in response to persistent inflammatory stimulation. In cancer patients, TLSs are generally associated with positive clinical outcomes. However, the cellular composition and spatial distribution of TLSs can vary depending on the underlying disease state, complicating interpretations of their prognostic significance. Murine models are indispensable for providing a deeper insight into the mechanisms involved in TLS formation and function. Studies using these models can complement current clinical efforts to characterize TLSs via genetic sequencing and histopathology of human samples. Several features of TLSs resemble that of secondary lymphoid organs (SLOs). Consequently, vascular system components and structural support elements are important for TLS formation and maintenance. Furthermore, TLSs in different tissue environments can exhibit distinct characteristics, necessitating careful consideration when selecting mouse models for study. Herein, we discuss critical aspects to consider when modeling TLSs and describe recent findings of TLS studies in the mouse lung and intestinal gut environments as examples to highlight the importance of considering tissue-specific regulatory mechanisms for TLSs. In this chapter, we also summarize the mechanistic insights derived from murine models on the formation and function of TLSs, which may translate to the future therapeutic modulation of TLS in disease.

Transcriptomic profiling with vascular tension analyses reveals molecular targets and phenotypes in preeclamptic placental vasculature

IntroductionThe placental vascular system plays an important role in the development of pregnancy hypertension in preeclampsia. The gene profiles of whole placental tissue (containing blood vessels and many other structural components) and pure vascular tissue should be very different. All previous reports using RNA-seq analysis in the placenta have tested its whole tissue or the villous part, and thus the gene profiles in the pure placental blood vessels are unknown.MethodsThis study was the first to address this point with RNA-seq in human placenta at the transcript level. Isolated placental micro-vessels from normal and preeclamptic pregnancies were used for RNA-seq analysis, real-time quantitative polymerase chain reaction (RT-qPCR) verification, and vascular function tests. Furthermore, a vascular function-centric core network was constructed to show the gene-gene interactions and gene-function associations in the placental vessel system.ResultsDifferential expression analysis identified a total of 486 significantly changed transcripts. Bioinformatics analysis further confirmed that multiple genes were highly related to blood vessel and placental phenotypes. Several hub genes, including ELMO1, YWHAE, and IL6ST, were significantly reduced in the placental vessels in preeclampsia. Vascular tension experiments showed that angiotensin II-mediated vasoconstriction and exogenous NO donor sodium nitroprusside-induced vasodilation were decreased, while phenylephrine-mediated vascular responses were unchanged in placental micro-vessels in preeclampsia.DiscussionThe results provide important insights into the pathological process in the placental vasculature in preeclampsia and offer great potential for further investigation of these molecular targets in the human placental vascular system.

Early and late phases of liver sinusoidal endothelial cell (LSEC) defenestration in mouse model of systemic inflammation.

Liver sinusoidal endothelial cells (LSECs) have transcellular pores, called fenestrations, participating in the bidirectional transport between the vascular system and liver parenchyma. Fenestrated LSECs indicate a healthy phenotype of liver while loss offenestrations (defenestration) in LSECs is associated with liver pathologies. We introduce a unique model of systemic inflammation triggered by the deletion ofMcpip1 in myeloid leukocytes (Mcpip1fl/flLysMCre) characterised by progressive alterations in LSEC phenotype. We implement multiparametric characterisation of LSECs by using novel real-time atomic force microscopy supported with scanning electron microscopy and quantitative fluorescence microscopy. In addition, we provide genetic profiling, searching for characteristic genes encoding proteins that might be connected with the structure of fenestrations. We demonstrate that LSECs in Mcpip1fl/flLysMCre display two phases of defenestration: the early phase, with modest defenestration that was fully reversible using cytochalasin B and the late phase, with severe defenestration that is mostly irreversible. By thorough analysis of LSEC porosity, elastic modulus and actin abundance in Mcpip1fl/flLysMCre and in response to cytochalasin B, we demonstrate that proteins other than actin must be additionally responsible for inducing open fenestrations. We highlight several genes that were severely affected in the late but not in the early phase of LSEC defenestration shedding a light on complex structure of individual fenestrations. The presented model of LSEC derived from Mcpip1fl/flLysMCre provides avaluable reference for developing novel strategies for LSEC refenestration in the early and late phases of liver pathology.

Angiogenesis of Avascular Necrosis of the Femoral Head: A Classic Treatment Strategy

Avascular necrosis of the femoral head (ANFH) is a type of osteonecrosis due to the cessation of blood supply, characterized by persistent local pain and collapse of the joint. The etiology of ANFH is multifaceted, and while its precise pathogenesis remains elusive, it is currently widely believed that the femoral head is highly dependent on the vascular system. A large number of studies have shown that vascular injury is the initial factor in the onset of ANFH. In this review, we briefly introduced the process of angiogenesis and the blood supply to the femoral head, with a focus on summarizing the existing research on promoting angiogenesis for the treatment of ANFH. We conclude that providing alternative pathways through angiogenesis to resolve the problem of the obstructed free flow of the blood is an important means of treating ANFH. Moreover, we also looked forward to the mechanism of endothelial metabolism, which has not yet been studied in femoral head necrosis models, providing potential strategies for more effective use of angiogenesis for the treatment of femoral head necrosis.

Phytochemicals and Their Nanoformulations for Targeting Hepatocellular Carcinoma: Exploring Potential and Targeting Strategies.

Hepatocellular carcinoma (HCC) continues to pose a global health concern, necessitating the exploration of innovative therapeutic approaches. In the recent decade, targeting tumor stroma consisting of extracellular matrix (ECM), immune cells, vascular system, hypoxia, and also suppressive mechanisms in HCC has attracted interest in repressing tumor growth and metastasis. Phytochemicals have attained considerable attention because of their manifold biological effects and high capacity for anticancer activities. These chemical agents have shown the capability to modulate different cells and secretions within the stroma of malignancies. In recent years, the development of nanoformulations has further enhanced the therapeutic potential of phytochemicals by improving their solubility, bioavailability, and targeted delivery to tumor tissues. This review aims to provide an encyclopedic overview of the potential of phytochemicals and their nanoformulations as promising therapeutic strategies for targeting HCC. The review initially highlights the broad array of phytochemicals exhibiting potent anticancer properties, including flavonoids, alkaloids, terpenoids, and phenolic compounds, among others. Then, the nanoformulations and modification of these agents will be reviewed. Finally, we will review the latest experiments that have examined the modulation of HCC using adjuvant phytochemicals and their nanoformulations.

Skeletal muscle reactive oxygen species and microvascular endothelial function in age-related hypertension: a study protocol using a microdialysis technique.

Increased reactive oxygen species (ROS) generation and microvascular endothelial disruptions occur with natural ageing, but often transpire before the detection of cardiometabolic conditions including hypertension. Age-related increases in blood pressure are driven by complex systemic changes with poorly understood integrated mechanisms. The deconditioning experienced by ageing skeletal muscle from mid-life is associated with reduced microvascular blood flow and increased peripheral resistance, suggesting that vasodilatory decrements in the muscle may precede the age-related increases in blood pressure. Structural and functional changes within the vascular and skeletal muscle systems with advancing age can influence redox homeostasis, and vice versa, further compounding microvascular endothelial dysfunction. Therefore, comparisons between the microvascular environments of healthy and hypertensive cohorts can provide insights into the changes that occur during significant periods of functional decline. This comprehensive study protocol describes a microdialysis technique to assess the interactions of microvascular health and functional changes in the muscle, which currently cannot be otherwise addressed. Here, we detail an experimental protocol to simultaneously detect skeletal muscle ROS (H2O2 and indirect O2 -), determine nutritive blood flow and assess microvascular endothelial function in response to acetylcholine stimulation. We expect that healthy middle-aged individuals should not have increased ROS generation in the muscle at rest, compared to their hypertensive or older counterparts, but may exhibit perturbed microvascular function. The described technique allows for intricate exploration of microvascular physiology that will provide a critically novel insight into benchmarking potential age-related mechanisms involved in the development of age-related hypertension, and aid in early identification and prevention. KEY POINTS: Increased reactive oxygen species (ROS) production and microvascular endothelial dysfunction precede the onset of age-related cardiometabolic and vascular conditions such as hypertension. The profound structural and functional changes that occur within the vasculature and in skeletal muscle from middle age prompt a need to mechanistically explore the microvascular environment in healthy and hypertensive individuals. Using a novel microdialysis technique, we detail an experimental protocol to simultaneously detect skeletal muscle ROS (H2O2 and indirect O2 -), determine nutritive blood flow and assess microvascular endothelial function in response to acetylcholine stimulation. With this technique and study protocol, we can reveal functional insights into potential perturbations in ROS generation at rest and the microvascular endothelium, which play important roles in the development of age-related hypertension.

The interplay between ferroptosis and inflammation: therapeutic implications for cerebral ischemia-reperfusion

Stroke ranks as the second most significant contributor to mortality worldwide and is a major factor in disability. Ischemic strokes account for 71% of all stroke incidences globally. The foremost approach to treating ischemic stroke prioritizes quick reperfusion, involving methods such as intravenous thrombolysis and endovascular thrombectomy. These techniques can reduce disability but necessitate immediate intervention. After cerebral ischemia, inflammation rapidly arises in the vascular system, producing pro-inflammatory signals that activate immune cells, which in turn worsen neuronal injury. Following reperfusion, an overload of intracellular iron triggers the Fenton reaction, resulting in an excess of free radicals that cause lipid peroxidation and damage to cellular membranes, ultimately leading to ferroptosis. The relationship between inflammation and ferroptosis is increasingly recognized as vital in the process of cerebral ischemia-reperfusion (I/R). Inflammatory processes disturb iron balance and encourage lipid peroxidation (LPO) through neuroglial cells, while also reducing the activity of antioxidant systems, contributing to ferroptosis. Furthermore, the lipid peroxidation products generated during ferroptosis, along with damage-associated molecular patterns (DAMPs) released from ruptured cell membranes, can incite inflammation. Given the complex relationship between ferroptosis and inflammation, investigating their interaction in brain I/R is crucial for understanding disease development and creating innovative therapeutic options. Consequently, this article will provide a comprehensive introduction of the mechanisms linking ferroptosis and neuroinflammation, as well as evaluate potential treatment modalities, with the goal of presenting various insights for alleviating brain I/R injury and exploring new therapeutic avenues.

A novel friction coefficient model parameters identification method for needle-tissue insertion procedure

Abstract In endoscopic liver vascular insertion surgeries, during the process of angiographic operation, the success of vascular staining depends on precise needle insertion control which heavily relies on experienced surgeons. Endoscopic vascular insertion surgical navigation system shows the potential to improve position precision, however it relies on needle-tissue interaction model and parameter identification to provide essential information for improving needle insertion accuracy, in which the friction coefficient is important parameters but difficult to determine. In this paper, a novel needle-tissue friction coefficient identification method was proposed with unknown tissue Young's modulus under endoscopic liver surgery scenarios. A modified friction coefficient model was proposed including the adhesion and elastic friction component to describe needle-tissue dynamic interaction process which can predict the friction coefficient more precisely. The proposed parameter estimation method based on the modified friction model can simultaneously estimate friction coefficient and Young's modulus. The proposed method was demonstrated by the friction coefficient measurement experiment. The results showed that the friction coefficient model prediction results agreed well with expected value. The proposed method can be applied to provide essential tissue-needle interactive information to improve needle insertion precision in the endoscopic liver vascular insertion surgery scenarios.

Advancements in Organoid Culture Technologies: Current Trends and Innovations.

Organoids have emerged as valuable tools in investigating disease mechanisms, drug efficacy, and personalized medicine due to their capacity to recapitulate crucial aspects of tissue physiology, including cell-cell interactions, heterogeneity, microenvironmental cues, and drug responses. Despite their broad applicability across various research domains, conventional organoid culture methods are plagued by several limitations that hinder research progress. These limitations include the inability to faithfully recreate tissue microenvironments, immune contexts, and vascular systems. Fortunately, ongoing advancements in organoid culture techniques are addressing these shortcomings. In this review, we provide a comprehensive overview of current mainstream organoid culture protocols. By evaluating these protocols, researchers can identify the most suitable experimental methods, thereby optimizing resource allocation and experimental outcomes.

Understanding the anatomical diversity of leaves in the Aspicarpoid clade: New insights for Malpighiaceae systematics

The Aspicarpoid clade represents a strongly supported group within the Stigmaphylloid lineage. The group is composed of four neotropical genera: Aspicarpa Rich., Gaudichaudia Kunth, Janusia A.Juss. and Peregrina W.R.Anderson. In this study, we studied the utility of leaf anatomy characters to support groups recovered in molecular phylogenies and define synapomorphies that can be used in future infra- and supra-generic classifications. Camarea axillaris A.St.-Hil. (1823: 10) and Cottsia Dubard &amp; Dop (1908: 20) were used as outgroups for comparison. Dry leaf samples were re-hydrated, sectioned, stained, and analyzed using a microscope and a stereomicroscope. Characters such as presence and absence of glands, their location and morphotype, petiole and midrib contour, presence of trichomes, accessory bundles, vascular system organization and mesophyll type were utilized for species comparison, showing high taxonomic value for the group. Leaf glands, accessory bundles, sheath extension in the mesophyll and presence of druses and prismatic crystals were the most valuable characters in an evolutionary approach for the clade. Our work confirms the power of leaf anatomy as a taxonomic and evolutionary tool in Malpighiaceae Juss. (1789: 252), as well as its contribution to the delimitation of phylogenetic groups in the Aspicarpoid clade.

In situ isotropic 3D imaging of vasculature perfusion specimens using x-ray microscopic dual-energy CT.

Ex vivo x-ray angiography provides high-resolution, three-dimensional information on vascular phenotypes down to the level of capillaries. Sample preparation for ex vivo angiography starts with the removal of blood from the vascular system, followed by perfusion with an x-ray dense contrast agent mixed with a carrier such as gelatine or a polymer. Subsequently, the vascular micro-architecture of harvested organs is imaged in the intact fixed organ. In the present study, we present novel microscopic dual-energy CT (microDECT) imaging protocols that allow to visualise and analyse microvasculature in situ with reference to the morphology of hard and soft tissue. We show that the spectral contrast of µAngiofil and Micropaque barium sulphate in perfused specimens allows for the effective separation of vasculature from mineralised skeletal tissues. Furthermore, we demonstrate the counterstaining of perfused specimens using established x-ray dense contrast agents to depict blood vessels together with the morphology of soft tissue. Phosphotungstic acid (PTA) is used as a counterstain that shows excellent spectral contrast in both µAngiofil and Micropaque barium sulphate-perfused specimens. A novel Sorensen-buffered PTA protocol is introduced as a counterstain for µAngiofil specimens, as the polyurethane polymer is susceptible to artefacts when using conventional staining solutions. Finally, we demonstrate that counterstained samples can be automatically processed into three separate image channels (skeletal tissue, vasculature and stained soft tissue), which offers multiple new options for data analysis. The presented microDECT workflows are suited as tools to screen and quantify microvasculature and can be implemented in various correlative imaging pipelines to target regions of interest for downstream light microscopic investigation.

Claudin2 is involved in the interaction between Megalocytivirus-induced virus-mock basement membrane (VMBM) and lymphatic endothelial cells

The genus Megalocytivirus, belonging to the family Iridoviridae, is one of the most detrimental virus groups to fish aquaculture. Megalocytivirus creates a virus-mock basement membrane (VMBM) on the surface of infected cells. This membrane provides attachment sites for lymphatic endothelial cells (LECs), disrupting fish's endothelial cell-extracellular matrix system. This disruption triggers injury to the vascular system and can result in death. Exploring the VMBM-cell interaction mechanism is crucial for uncovering the pathogenesis of Megalocytivirus and identifying therapeutic targets. Claudins, a class of tetra transmembrane proteins, play a key role in creating tight junctions between endothelial or epithelial cells. In this study, we demonstrated that the expression of Claudin2, a member of the Claudin family in fish, was significantly up-regulated by Megalocytivirus infection. Claudin2 was found in LECs attached to the surface of infected cells. It interacted with the VMBM viral components VP23R, VP08R, and VP33L at multiple binding sites through its two extracellular loops. However, it did not interact with the host basement membrane’s nidogen. Therefore, Claudin2 is involved in the interaction of LEC with VMBM and plays a role in the disturbed distribution of extracellular matrix and endothelial cells in Megalocytivirus-infected fish tissues. This study aims to uncover the molecular mechanisms by which Megalocytivirus infection leads to pathological changes in the vascular system.

Effects of systemic ventricular assist in failing Fontan patients: a theoretical analysis using a computational model

Mechanical circulatory support is a potential treatment for failing Fontan patients. In this study, we performed a theoretical analysis using a computational model to clarify the effects of systemic ventricular assist device (VAD) in failing Fontan patients. Cardiac chambers and vascular systems were described using the time-varying elastance model and modified Windkessel model, respectively. A VAD was simulated as a nonlinear function. In systolic and diastolic ventricular dysfunction and atrioventricular valve regurgitation models, systemic VAD increased the cardiac index and decreased the central venous pressure (CVP). However, in the high pulmonary vascular resistance model, CVP became extremely high above 15 mmHg to maintain the cardiac index when the pulmonary vascular resistance index (PVRI) was above 5 Wood units m2. In Fontan patients with ventricular dysfunction or atrioventricular valve regurgitation, systemic VAD efficiently improves the hemodynamics. In Fontan patients with PVRI of > 5 Wood units m2, systemic VAD seems ineffective.

Mechanism of CXCL8 regulation of methionine metabolism to promote angiogenesis in gliomas

BackgroundGliomas are the most common malignant brain tumors characterized by angiogenesis and invasive growth. A detailed understanding of its molecular characteristics could provide potential therapeutic targets. In the present study, we sought to explore the key gene CXCL8 in methionine metabolism in gliomas and its potential role in angiogenesis.MethodsU251 glioma cells were divided into control and methionine-restriction tolerant (constructed with 1/4 of the standard level of methionine in the culture medium) groups for transcriptome and metabolome analysis. To confirm the functions and mechanism of CXCL8 in glioma, heat map, volcano map, Go enrichment, gene set enrichment analysis (GSEA), protein–protein interaction network analysis, RT-PCR, western blotting assays, chicken embryo chorioallantoic membrane (CAM) test, chicken embryo yolk sac membrane (YSM) test and transplantation tumor nude mice model were performed. The TCGA database, CGGA database and clinical tissue samples were used to analyze CXCL8’s significance on prognosis for patients with glioma.ResultsCXCL8 expression was significantly up-regulated in methionine-restricted tolerance cells, it also activated vascular system development and triggered angiogenesis. CXCL8 expression is negatively correlated with survival prognosis in gliomas.ConclusionsGlioma cells promote angiogenesis in methionine-restricted environments through the activation of CXCL8, compensating for nutrient deprivation, and possibly contributing to the failure of antiangiogenic therapy.

The role for ω-3 polyunsaturated and short chain fatty acids in hypertension: an updated view on the interaction with gut microbiota

As of 2024, arterial hypertension is still considered the leading modifiable cardiovascular risk factor and, due to high rates of undertreatment and poor blood pressure control, the major contributor to human morbidity and mortality. Development of new treatment options and better interventions in lifestyle correction have become a priority of experimental and clinical research. In the last decades, dietary supplementation of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) and generation of gut microbiota-derived short chain fatty acids (SCFAs) have surged as potential and promising interventions for hypertension and cardiovascular prevention. ω-3 PUFAs are considered “essential” fatty acids that can be obtained only from dietary sources. Although previous intervention trials were not consistent in reporting a significant benefit of ω-3 PUFAs, the recent REDUCE-IT trial has provided robust evidence in support of their role in cardiovascular prevention. Recent studies have also identified the intestinal microbiota as a potential player in the pathophysiology and progression of hypertension. Although this might occur through many pathways, generation of SCFAs that is highly dependent on dietary fiber intake is primarily involved, providing an additional target for the development of novel therapeutic strategies. For these reasons, some scientific societies currently recommend dietary supplementation of ω-3 PUFAs and fiber-containing foods in patients with hypertension. In this narrative review, we summarize the results of studies that examined the effects of ω-3 PUFAs and SCFAs on blood pressure, highlighting the mechanisms of action on the vascular system and their possible impact on hypertension, hypertension-related organ damage and, ultimately, cardiovascular outcomes.

Identification of Vascular Genes Differentially Expressed in the Brain of Patients with Alzheimer's Disease.

Alzheimer's disease (AD) plays a prominent role as the most common form of dementia. Moreover, the traditional mechanism of AD does not explain the microvascular damage observed in about 25-30 years between the onset of AD, which results in late application treatment that inhibits or delays neurodegeneration. Our objective was to identify differentially expressed genes in human brain samples associated with vascular disruption in AD. We analyzed 1633 post-mortem brain samples in the GEO to database and, after applying clinical and bioinformatic exclusion criteria, worked with 581 prefrontal and frontal samples. All datasets were analyzed using GEO2R from NCBI. We identified common genes using the Venny tool, and their metabolic relevance associated with AD and the vascular system was analyzed using MetaboAnalyst tools. Our bioinformatic analysis identified PRKCB, MAP2K2, ADCY1, GNA11, GNAQ, PRKACB, KCNMB4, CALD1, and GNAS as potentially involved in AD pathogenesis. These genes are associated with signal transductions, cell death signaling, and cytoskeleton, suggesting potential modulation of cellular physiology, including endoplasmic reticulum and mitochondrial activity. This study generates hypotheses regarding the roles of novel genes over critical pathways relevant to AD and its relation with vascular dysfunction. These findings suggest potential new targets for further investigation into the pathogenesis of dementia and AD.