Endothelial Wall Research Articles

Minocycline prevents monocrotaline-induced pulmonary hypertension through the attenuation of endothelial dysfunction and vascular wall thickening

Minocycline prevents monocrotaline-induced pulmonary hypertension through the attenuation of endothelial dysfunction and vascular wall thickening

High-Resolution Modeling of Aqueous Humor Dynamics in the Conventional Outflow Pathway of a Normal Human Donor Eye

Background and Objective: The conventional aqueous outflow pathway, which includes the trabecular meshwork (TM), juxtacanalicular tissue (JCT), and inner wall endothelium of Schlemm's canal (SC) and its basement membrane, plays a significant role in regulating intraocular pressure (IOP) by controlling aqueous humor outflow resistance. Despite its significance, the biomechanical and hydrodynamic properties of this region remain inadequately understood. Fluid-structure interaction (FSI) and computational fluid dynamics (CFD) modeling using high-resolution microstructural images of the outflow pathway provides a comprehensive method to estimate these properties under varying conditions, offering valuable understandings beyond the capabilities of current imaging techniques.Methods: In this study, we utilized high-resolution 3D serial block-face scanning electron microscopy (SBF-SEM) to image the TM/JCT/SC complex of a normal human donor eye perfusion-fixed at an IOP of 7 mm Hg. We developed a detailed 3D finite element (FE) model of the pathway using SBF-SEM images to simulate the biomechanical environment. The model included the TM/JCT/SC complex (structure) with interspersed aqueous humor (fluid). We employed a 3D, inverse FE algorithm to calculate the unloaded geometry of the TM/JCT/SC complex and utilized FSI to simulate the pressurization of the complex from 0 to 15 mm Hg.Results: Our simulations revealed that the resultant velocity distribution in the aqueous humor across the TM/JCT/SC complex is heterogeneous. The JCT and its deepest regions, specifically the basement membrane of the inner wall of SC, exhibited a volumetric average velocity of ∼0.011 mm/s, which is higher than the TM regions, with a volumetric average velocity of ∼0.007 mm/s. Shear stress analysis indicated that the maximum shear stress, based on our FE code criteria, was 0.5 Pa starting from 10 µm into the TM from the anterior chamber and increased to 0.95 Pa in the JCT and its adjacent SC inner wall basement membrane. Also, the tensile stress and strain distributions showed significant variations, with the first principal stress reaching up to 57 Pa (compressive volumetric average) and the first principal strain reaching up to 3.5% in areas of high mechanical loading. The resultant stresses, strains, and velocities exhibited relatively similar average values across the TM, JCT, and SC regions, primarily due to the uniform elastic moduli assigned to these components. Our computational fluid dynamics (CFD) analysis revealed that while the velocity of the aqueous humor remained consistent, the maximum shear stress was reduced by a factor of thirty.Conclusion: The uneven distribution of shear stress and velocity within the TM/JCT/SC complex highlights the complex biomechanical environment that regulates aqueous humor outflow.

Retinal G-protein-coupled receptor deletion exacerbates AMD-like changes via the PINK1-parkin pathway under oxidative stress.

The intake of high dietary fat has been correlated with the progression of age-related macular degeneration (AMD), affecting the function of the retinal pigment epithelium through oxidative stress. A high-fat diet (HFD) can lead to lipid metabolism disorders, excessive production of circulating free fatty acids, and systemic inflammation by aggravating the degree of oxidative stress. Deletion of the retinal G-protein-coupled receptor (RGR-d) has been identified in drusen. In this study, we investigated how the RGR-d exacerbates AMD-like changes under oxidative stress, both invivo and invitro. Fundus atrophy became evident, at 12 months old, particularly in the RGR-d + HFD group, and fluorescence angiography revealed narrower retinal vessels and a reduced perfusion area in the peripheral retina. Although rod electroretinography revealed decreasing trends in the a- and b-wave amplitudes in the RGR-d + HFD group at 12 months, the changes were not statistically significant. Mice in the RGR-d + HFD group showed a significantly thinner and more fragile retinal morphology than those in the WT + HFD group, with disordered and discontinuous pigment distribution in the RGR-d + HFD mice. Transmission electron microscopy revealed a thickened Bruch's membrane along the choriocapillaris endothelial cell wall in the RGR-d + HFD mice, and the outer nuclear layer structure appeared disorganized, with reduced nuclear density. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated significantly lower levels of 25(OH)-vitamin D3 metabolites in the RGR-d + HFD group. Under oxidative stress, RGR-d localized to the mitochondria and reduced the levels of the PINK1-parkin pathway. RGR-d mice fed an HFD were used as a new animal model of dry AMD. Under high-fat-induced oxidative stress, RGR-d accumulated in the mitochondria, disrupting normal mitophagy and causing cellular damage, thus exacerbating AMD-like changes both invivo and invitro.

Impact of Age on Ultrastructural Changes in Internal Thoracic Artery in Patients Undergoing Coronary Artery Bypass Grafting

AIM: Age is a known risk factor for cardiovascular disease and plays a role in the atherosclerotic process. The purpose of this study was to look at the impact of aging and associated risk factors on the ultrastructure of internal thoracic arteries in patients undergoing coronary artery bypass grafting. MATERIALS&METHODS: We enrolled 27 patients undergoing elective coronary artery bypass grafting at our institute between August-October 2018. Age groups were classified into three: 50-59, 60-69, and 70-79 years. A 2-mm distal portion of the vessel was excised when the ITA was surgically harvested. Transmission electron microscopy was used to investigate the ultrastructural changes. Cell structure, tissue edema, and endothelial mitochondria were all assessed and rated by using semiquantitative analysis. RESULTS: The ultrastructure of the vessel wall exhibited no significant changes in Group-I. Endothelial wall irregularity with endothelial cells of varying thickness was seen in Group-II. Group-III showed subendothelial edema and localized endothelial wall discontinuity. These changes were particularly severe in the elderly and patients with comorbidities. The greatest permanent cell alterations, such as massive vacuoles and organelle loss, were identified in two patients with kidney failure and hypertension. The average scores assessing the severity of changes in endotohelial cell structure (P  .001), tissue edema (P  .001), and mitochondria (P  .001) were significantly different between groups showing more severe changes with aging. CONCLUSIONS: In elderly patients with comorbidities, the ITA endothelium may exhibit severe ultrastructural alterations, with the most permanent abnormalities reported in those with hypertension and kidney failure. However, The ITA remains the gold standard in CABG with its native resistance to atherosclerosis.

Investigation of Type A Aortic Dissection Using Computational Modelling.

Aortic dissection is a catastrophic failure of the endothelial wall that could lead to malperfusion or rupture. Computational modelling tools may help detect arterial damage. Technological advancements have led to more sophisticated forms of modelling being made available to low-grade computers. These devices can create 3D models with clinical data, where the clinical blood pressure waveforms' model can be used to form boundary conditions for assessing hemodynamic parameters, modelling blood flow propagation along the aorta to predict the development of cardiovascular disease. This study presents patient-specific data for a rare case of severe Type A aortic dissection. CT scan images were taken nine months apart, consisting of the artery both before and after dissection. The results for the pre-dissection CT showed that the pressure waveform at the ascending aorta was higher, and the systolic pressure was lagging at the descending aorta. For the post-dissection analysis, we observed the same outcome; however, the amplitude for the waveform (systolic pressure) at the ascending aorta increased in the false lumen by 25% compared to the true lumen by 3%. Also, the waveform peak (systolic) was leading by 0.01 s. The hemodynamic parameter of wall shear stress (WSS) predicted the aneurysm's existence at the ascending aorta, as well as potential aortic dissection. The high WSS contours were located at the tear location at the peak blood flow of 0.14 s, which shows the potential of this tool for earlier diagnosis of aortic dissection.

The role of pharmacological interventions in managing hyperlipidemia: A closer look at different drugs

Hyperlipidemia is a medical condition characterized by an increase in plasma lipids, including triglycerides, cholesterol, cholesterol esters, phospholipids, and plasma lipoproteins, which is a leading risk factor for cardiovascular diseases. The pathophysiology of hyperlipidemia is influenced by endothelial damage to blood vessels, leading to a loss of nitric oxide, increased inflammation, and lipid accumulation in the deepest layer of the endothelial wall. Lipid-lowering drugs like statins can reduce LDL levels by 25-60%, but they have negative impacts on clinical outcomes. Lipoprotein metabolism involves various enzymes, and atherosclerosis accumulates fat, cholesterol, and calcium in artery linings, creating fibrous plaques that reduce blood flow and oxygen supply, leading to heart damage and death. Lipoprotein metabolism involves various enzymes, including lipoprotein lipase (LPL), hepatic lipase (HL), lecithin cholesterol acyl transferase (LCAT), cholesterol ester transfer protein (CETP), microsomal triglyceride protein (MTP), and acyl Co-A transferase (ACAT). Atherosclerosis accumulates fat, cholesterol, and calcium in artery linings, creating fibrous plaques. This leads to reduced blood flow and oxygen supply, causing heart damage and death. Reducing LDL and total cholesterol can significantly lower the incidence of strokes. Reducing LDL and total cholesterol can significantly lower the incidence of strokes. Traditional antihyperlipidemic medicines have negative effects, and herbal treatments like onion, garlic, guggul, and Asparagus racemosus have been shown to have anti-diabetic and antihyperlipidemic properties.

Current and Emerging Approaches for Primary Prevention of Coronary Artery Disease Using Cardiac Computed Tomography.

To summarize the current use of cardiac computed tomography (CT) technologies as well as their pertinent evidence in regards to prevention of coronary artery disease (CAD). Cardiac CTA has now become a main non-invasive method for the evaluation of symptomatic CAD. In addition to coronary calcium score, other CT technologies such as atherosclerotic plaque analysis, fractional flow reserve estimation by CT, pericoronary fat attenuation, and endothelial wall shear stress have emerged. Whether the use of CT modalities can enhance risk prediction and prevention in CAD has not been fully answered. We discuss the evidence for coronary artery calcium scoring and coronary CT angiography in primary prevention and the current barriers to their use. We attempt to delineate what can be done to expand use and what studies are needed to broaden adoption in the future. We also examine the potential roles of emerging CT technologies. Finally, we describe potential clinical approaches to prevention that would incorporate cardiac CT technologies.

Free Fatty Acids and Free Fatty Acid Receptors: Role in Regulating Arterial Function.

The metabolic network's primary sources of free fatty acids (FFAs) are long- and medium-chain fatty acids of triglyceride origin and short-chain fatty acids produced by intestinal microorganisms through dietary fibre fermentation. Recent studies have demonstrated that FFAs not only serve as an energy source for the body's metabolism but also participate in regulating arterial function. Excess FFAs have been shown to lead to endothelial dysfunction, vascular hypertrophy, and vessel wall stiffness, which are important triggers of arterial hypertension and atherosclerosis. Nevertheless, free fatty acid receptors (FFARs) are involved in the regulation of arterial functions, including the proliferation, differentiation, migration, apoptosis, inflammation, and angiogenesis of vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs). They actively regulate hypertension, endothelial dysfunction, and atherosclerosis. The objective of this review is to examine the roles and heterogeneity of FFAs and FFARs in the regulation of arterial function, with a view to identifying the points of intersection between their actions and providing new insights into the prevention and treatment of diseases associated with arterial dysfunction, as well as the development of targeted drugs.

Charting the course of blood flow: vessel-on-a-chip technologies in thrombosis studies

Cardiovascular diseases, primarily driven by thrombosis, remain the leading cause of global mortality. Although traditional cell culture and animal models have provided foundational insights, they often fail to capture the complex pathophysiology of thrombosis, which hinders the development of targeted therapies for cardiovascular diseases. The advent of microfluidics and vascular tissue engineering has propelled the advancement of vessel-on-a-chip technologies, which enable the simulation of the key aspects of Virchow’s Triad: hypercoagulability, alteration in blood flow, and endothelial wall injury. With the ability to replicate patient-specific vascular architectures and hemodynamic conditions, vessel-on-a-chip models offer unprecedented insights into the mechanisms underlying thrombosis formation and progression. This review explores the evolution of microfluidic technologies in thrombosis research, highlighting breakthroughs in endothelialized devices and their roles in emulating conditions such as vessel stenosis, flow reversal, and endothelial damage. The limitations and challenges of the current vessel-on-a-chip systems are addressed, and future perspectives on the potential for personalized medicine and targeted therapies are presented. Vessel-on-a-chip technology holds immense potential for revolutionizing thrombosis research, enabling the development of targeted, patient-specific diagnostic tools and therapeutic strategies. Realizing this potential will require interdisciplinary collaboration and continued innovation in the fields of microfluidics and vascular tissue engineering.

Effect of Aspirin Use on the Adverse Outcomes in Patients Hospitalized for COVID-19.

Coronavirus disease 2019 (COVID-19) triggers multiple components of the immune system and causes inflammation of endothelial walls across vascular beds, resulting in respiratory failure, arterial and venous thrombosis, myocardial injury, and multi-organ failure leading to death. Early in the COVID-19 pandemic, aspirin was suggested for the treatment of symptomatic individuals, given its analgesic, antipyretic, anti-inflammatory, anti-thrombotic, and antiviral effects. This study aimed to evaluate the association of aspirin use with various clinical outcomes in patients hospitalized for COVID-19. This was a retrospective study involving patients aged ≥ 18 years and hospitalized for COVID-19 from March 2020 to October 2020. Primary outcomes were acute cardiovascular events (ST elevation myocardial infarction (STEMI), type 1 non-ST elevation myocardial infarction (NSTEMI), acute congestive heart failure (CHF), and acute stroke) and death. Secondary outcomes were respiratory failure, need for mechanical ventilation, and acute deep vein thrombosis (DVT)/pulmonary embolism (PE). Of 376 patients hospitalized for COVID-19, 128 were taking aspirin. Significant proportions of native Americans were hospitalized for COVID-19 in both aspirin (22.7%) and non-aspirin (24.6%) groups. Between aspirin and non-aspirin groups, no significant differences were found with regard to mechanical ventilator support (21.1% vs. 15.3%, P = 0.16), acute cardiovascular events (7.8% vs. 5.2%, P = 0.32), acute DVT/PE (3.9% vs. 5.2%, P = 0.9), readmission rate (13.3% vs. 12.9%, P = 0.91) and mortality (23.4% vs. 20.2%, P = 0.5); however, the median duration of mechanical ventilation was significantly shorter (7 vs. 9 days, P = 0.04) and median length of hospitalization was significantly longer (5.5 vs. 4 days, P = 0.01) in aspirin group compared to non-aspirin group. No significant differences were found in acute cardiovascular events, acute DVT/PE, mechanical ventilator support, and mortality rate between hospitalized COVID-19 patients who were taking aspirin compared to those not taking aspirin. However, larger studies are required to confirm our findings.

APEX2-based proximity proteomic analysis identifies candidate interactors for Plasmodium falciparum knob-associated histidine-rich protein in infected erythrocytes

The interaction of Plasmodium falciparum—infected red blood cells (iRBCs) with the vascular endothelium plays a crucial role in malaria pathology and disease. KAHRP is an exported P. falciparum protein involved in iRBC remodelling, which is essential for the formation of protrusions or “knobs” on the iRBC surface. These knobs and the proteins that are concentrated within them allow the parasites to escape the immune response and host spleen clearance by mediating cytoadherence of the iRBC to the endothelial wall, but this also slows down blood circulation, leading in some cases to severe cerebral and placental complications. In this work, we have applied genetic and biochemical tools to identify proteins that interact with P. falciparum KAHRP using enhanced ascorbate peroxidase 2 (APEX2) proximity-dependent biotinylation and label-free shotgun proteomics. A total of 30 potential KAHRP-interacting candidates were identified, based on the assigned fragmented biotinylated ions. Several identified proteins have been previously reported to be part of the Maurer’s clefts and knobs, where KAHRP resides. This study may contribute to a broader understanding of P. falciparum protein trafficking and knob architecture and shows for the first time the feasibility of using APEX2-proximity labelling in iRBCs.

Neuro-inflammatory interactions as a mediator of the Exaggerated Exercise Pressor Reflex (EPR) in a mouse model of Peripheral Artery Disease

Introduction and rationale: The Exercise pressor reflex (EPR) is a physiological mechanism in which the contraction of skeletal muscle results in a rise in heart rate (HR) and mean arterial pressure (MAP). In patients with Peripheral Artery Disease (PAD), this reflex is exaggerated, leading to abnormally high elevations in blood pressure during exercise. These cardiovascular responses in patients with PAD have been linked to increased morbidity and mortality, thus limiting the prescription of exercise for these patients. Using a novel murine model of the EPR, our laboratory has demonstrated that mice with femoral artery ligation (a well-established model of PAD), exhibit augmented increases in MAP which is mediated by PIEZO2 positive, mechanosensitive afferent neurons. We have demonstrated that inhibition of PIEZO2 expressing channels normalizes the MAP response to exercise. Patients with PAD also display increased macrophage infiltration in their ischemia-injured limbs, indicating a pro-inflammatory environment. Sensory neurons have been reported to detect various signals produced by immune cells including IL-1β and TNFα. The immune-derived signals can sensitize the peripheral terminals of the sensory neurons, thereby reducing their firing threshold and increasing their responsiveness. Previous studies have also reported the enhancement of Piezo2-mediated mechanosensitive currents in the presence of inflammatory signals. Hypothesis: We, therefore, hypothesize that in mice with femoral artery ligation, muscle inflammation increases the expression and activation of resident ion channels (e.g., Piezo2) in mechanosensitive afferent neurons to mediate the exaggerated EPR in PAD.Study objective: To mechanistically investigate the interaction between muscle inflammation and Piezo2 in mechanosensitive afferent neurons.Methods: We performed sham surgery or ligation of the femoral artery ipsilaterally in C57BL/6 mice. After 72 hours, we harvested the gastrocnemius muscle for histological and molecular analyses.Data and summary and results: Our preliminary findings reveal that there is significantly increased expression of pro-inflammatory genes and infiltrating immune cells in the ischemic muscle when compared to non-ischemic muscle.Specifically, H&E staining revealed the presence and accumulation of inflammatory cells, including macrophages, in the ischemic muscle compared to control, along with observed necrosis. Transcript analysis of the ischemic gastrocnemius muscle showed significantly increased IL-1β and TNFα, two pan-proinflammatory genes that encode cytokines released by macrophages. TNFα is known to induce the synthesis of adhesion molecules (E-selectin and ICAM-1) on endothelial cells, allowing leukocytes to adhere and cross the endothelial wall into the injured tissue. Indeed, we observed significantly increased ICAM-1 and E-selectin transcripts in the ischemic muscle compared to controls. MCP1, a well-established chemokine, was also significantly increased, further emphasizing the recruitment of leukocytes to the ischemic muscle. In addition, inducible NOS ( iNOS), which is known to be expressed in IL-1β- and TNFα-rich proinflammatory environment was also significantly increased in our FAL model compared to Sham. These data establish that the ischemic muscle of a femoral-artery ligated mouse has a high proinflammatory phenotype. We are currently exploring the impact of proinflammatory mediators on Piezo2 channel expression and activity, as well as the effect of macrophage depletion on Piezo2 in afferent neurons. The data from these studies will provide novel insights regarding the influence of neuroimmune interactions on cardiovascular responses to exercise in PAD. These data hold the potential to reveal innovative therapies enabling safe prescription of exercise, thus alleviating the burden of PAD, and improving the quality of life for those affected by this condition. Internal sources. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

E-selectin is associated with stable angina and myocardial infarction in a sample of Kurdish population.

Endothelial dysfunction is the main factor that causes the onset of CAD. Leukocyte adhesion to the endothelium of the active blood artery wall has been demonstrated to be one of the early indicators of arteriosclerosis. This process is regulated by selectins. The purpose of this study is to ascertain the relationship between the polymorphisms in the E-selectin gene that have been linked to ischemic heart disease. We looked at the functional impact of the E-selectin gene polymorphism 7170G>C in Iraqi patients with IHD. This study was conducted on 200 participants who were admitted to the surgical specialty hospital-cardiac center in Erbil City, Iraq between October 2021 and May 2022. Based on the outcomes of the clinical examination, laboratory tests, coronary angiography (COA), acute myocardial infarction (MI) type ST-elevation myocardial infarction (STEMI), stable angina pectoris (SAP), and healthy control groups were tested. Each sample was subjected to Sanger sequencing. The polymorphism was significantly linked to stable angina and myocardial infarction Genotype CC was higher in SAP when compared with MI and control groups which was statistically significant with (p-value<0.05). A higher proportion of C allele was observed in SAP patients (15.7%) which was significantly higher than MI (14.58%) and control (10.8%). The statistical chi-square analysis for allele G frequency showed insignificant differences (p-value>0.05) between patients and the control group. Genetic variation in E-selectin such as polymorphism in nucleotide 7170 G>C at exon 4 region can significantly affect the outcome of cardiovascular diseases.

Determinants of Risk Factors Associated with Aortic Atherosclerosis: A Quantitative Study in Forensic Autopsies

ABSTRACT: Background: Cardiovascular diseases have become a major burden in the whole world and the top of it is atherosclerosis causing deaths. It is characterized as the thickening of the arterial walls with the fatty material which includes cholesterol, cellular wastes, and fibrin. The atherosclerosis can be hereditary, due to aging, any autoimmune disease causing inflammation of endothelial or because of the sedentary lifestyle. Atherosclerosis is a consequence of dysfunction of endothelial done by low-density lipoprotein and changes in it by the internal wall of arteries. Smoking increases the oxidation stress and decreases the accessibility of nitric oxide to the endothelial wall which leads to vasodilatory response. These changes are irreversible. Pre-mature aging also contributes to the destruction of the epithelial wall of arteries eventually leading to hypertension, which if left untreated can cause atherosclerosis. Method: This is a cross-sectional study conducted for a period of one year and the sample size of 110 was taken of which 65.5% were male and the rest were females. This study includes all those patients` bodies who can go through autopsy and excludes patients whose bodies are mutilated or decomposed or those patients` bodies whose history is not properly available. Consents were taken from the relatives of the victims. The autopsy was done after the proper identification and examination of the patient`s body. The thoracic cavity was cut and opened. The aorta was cut from its origin to the diaphragm. The operational criterion was determined by grading from 1 to 5 based on the severity and thickness of aortic atherosclerosis. The data was statistically analyzed by applying the student`s t-test. The significant value of p&lt;0.01 was considered. Result: Mostly males were affected. Out of 110 deceased more than 50% were from rural areas. 58% of the population have grade 1 and grade 2 atheromatous plaques. Most affected males were in the age of 50 years to 59 years and females were most affected in 60years to 69 years in their lifetime. This study also reveals that out of 110 dead bodies 64 patients died due to cardiac issues the rest died due to non-cardiac causes. The study also tells about the direct relation of atherosclerosis with hypertension, hyperlipidemia, hyperglycemia, and smoking habits with a significance level of p&lt;0.001. Conclusion: The present study shows that it is more common in males than females and victims belonged to the age group of 5th to 8th decade. This reveals that aging is the dominating factor of residence. Rural people have it more than urban due to lack of awareness and diagnostic facilities Also a direct correlation between atherosclerosis and hypertension, hyperlipidemia, hyperglycemia, and smoking has been seen and confirmed through statistical significant.

A Systematic Review and Meta-Analysis of the Pathology Underlying Aneurysm Enhancement on Vessel Wall Imaging.

Intracranial aneurysms are common, but only a minority rupture and cause subarachnoid haemorrhage, presenting a dilemma regarding which to treat. Vessel wall imaging (VWI) is a contrast-enhanced magnetic resonance imaging (MRI) technique used to identify unstable aneurysms. The pathological basis of MR enhancement of aneurysms is the subject of debate. This review synthesises the literature to determine the pathological basis of VWI enhancement. PubMed and Embase searches were performed for studies reporting VWI of intracranial aneurysms and their correlated histological analysis. The risk of bias was assessed. Calculations of interdependence, univariate and multivariate analysis were performed. Of 228 publications identified, 7 met the eligibility criteria. Individual aneurysm data were extracted for 72 out of a total of 81 aneurysms. Univariate analysis showed macrophage markers (CD68 and MPO, p = 0.001 and p = 0.002), endothelial cell markers (CD34 and CD31, p = 0.007 and p = 0.003), glycans (Alcian blue, p = 0.003) and wall thickness (p = 0.030) were positively associated with enhancement. Aneurysm enhancement therefore appears to be associated with inflammatory infiltrate and neovascularisation. However, all these markers are correlated with each other, and the literature is limited in terms of the numbers of aneurysms analysed and the parameters considered. The data are therefore insufficient to determine if these associations are independent of each other or of aneurysm size, wall thickness and rupture status. Thus, the cause of aneurysm-wall enhancement currently remains unknown.

Evaluation of biophysical alterations in the epithelial and endothelial layer of patients with Bullous Keratopathy

The cornea is a fundamental ocular tissue for the sense of sight. Thanks to it, the refraction of two-thirds of light manages to participate in the visual process and protect against mechanical damage. Because it is transparent, avascular, and innervated, the cornea comprises five main layers: Epithelium, Bowman's layer, stroma, Descemet's membrane, and endothelium. Each layer plays a key role in the functionality and maintenance of ocular tissue, providing unique ultrastructural and biomechanical properties. Bullous Keratopathy (BK) is an endothelial dysfunction that leads to corneal edema, loss of visual acuity, epithelial blisters, and severe pain, among other symptoms. The corneal layers are subject to changes in their biophysical properties promoted by Keratopathy. In this context, the Atomic Force Microscopy (AFM) technique in air was used to investigate the anterior epithelial surface and the posterior endothelial surface, healthy and with BK, using a triangular silicone tip with a nominal spring constant of 0.4 N/m. Six human corneas (n = 6) samples were used for each analyzed group. Roughness data, calculated by third-order polynomial adjustment, adhesion, and Young's modulus, were obtained to serve as a comparison and identification of morphological and biomechanical changes possibly associated with the pathology, such as craters and in the epithelial layer and exposure of a fibrotic layer due to loss of the endothelial cell wall. Endothelial cell membrane area and volume data were calculated, obtaining a relevant comparison between the control and patient. Such results may provide new data on the physical properties of the ocular tissue to understand the physiology of the cornea when it has pathology.

SALTWATER FISH CONSUMPTION AND THE RISK OF STROKE IN COASTAL POPULATION

Indonesia, consisting of tens of thousands of islands, has a rather long coastline with relatively high percentage of it is population that lives in the coastal area. High consumption of saltwater fish in the coastal population is an inevitability. Several studies have observed a relation between saltwater fish consumption and the risk of stroke with contradicting results, protective effect on one side and harmful on the other. The protective effect is mainly mediated by the poly-unsaturated fatty acid (PUFA) content of the saltwater fish while the harmful effect is mediated by the sodium content. PUFA exerts its protective effect through it is antioxidant effect on the endothelial wall, anti-inflammatory effect and the activation of anti-apoptotic pathways in the state of ischemic stroke while sodium increases the risk of hypertension which is the main predisposing factor for stroke and induces anatomical remodeling of the endothelial wall as well as functional abnormalities. Several public health interventions have been carried out to mitigate the harmful effect of the sodium content of saltwater fish yet there hasn’t been a specific intervention for coastal population.

Do Blood group and Sickle cell trait protect against placental malaria?

Blood group O is reported to confer some degree of protection from severe malaria in endemic setting. This protection is believed to be due to reduced and smaller rosette formation in people of blood group O which can easily be cleared by the host immune system. Also, sickle cell trait (HbAS) is reported to disrupt the adhesion of infected erythrocytes to microvascular endothelial walls, which could protect pregnant women from placental malaria. We determined the association between HbAS and ABO blood group, and placental malaria amongst pregnant women of all parities. The study enrolled 221 pregnant women. Peripheral blood samples were taken for malaria smears, ABO blood grouping and haemoglobin (Hb) electrophoresis. A struc‑ tured questionnaire was used to age, bed net usage, and the number of Sulphadoxine‑pyrimethamine (SP) doses taken by a pregnant woman. Two hundred and twenty‑one (221) pregnant women were enrolled and out of this number, 110 (49.8%) were primiparae and 111 (50.2%) multiparae, with a mean age of 23.7±5.2. Placental malaria (PM) prevalence by PCR detection was 19.4% (43/221). Of those who were malaria positive 58.1% (25/43) were primiparae. Primiparae who are of blood group O were more susceptible to PM [P=0.04, (OR); 2.85, 95% (Cl), 1.12‑9.01]. But sickle cell trait did not reduce the prevalence of PM [P=0.84 (OR); 0.92, 95% (Cl), 0.43‑1.99]. Non‑blood group O primiparae women were protected against placental malaria. This could be why some primiparae women are protected from PM, just like multiparae women.

Do Blood group and Sickle cell trait protect against placental malaria?

Blood group O is reported to confer some degree of protection from severe malaria in endemic setting. This protection is believed to be due to reduced and smaller rosette formation in people of blood group O which can easily be cleared by the host immune system. Also, sickle cell trait (HbAS) is reported to disrupt the adhesion of infected erythrocytes to microvascular endothelial walls, which could protect pregnant women from placental malaria. We determined the association between HbAS and ABO blood group, and placental malaria amongst pregnant women of all parities. The study enrolled 221 pregnant women. Peripheral blood samples were taken for malaria smears, ABO blood grouping and haemoglobin (Hb) electrophoresis. A structured questionnaire was used to age, bed net usage, and the number of Sulphadoxine-pyrimethamine (SP) doses taken by a pregnant woman. Two hundred and twenty-one (221) pregnant women were enrolled and out of this number, 110 (49.8%) were primiparae and 111 (50.2%) multiparae, with a mean age of 23.7±5.2. Placental malaria (PM) prevalence by PCR detection was 19.4% (43/221). Of those who were malaria positive 58.1% (25/43) were primiparae. Primiparae who are of blood group O were more susceptible to PM [P=0.04, (OR); 2.85, 95% (Cl), 1.12-9.01]. But sickle cell trait did not reduce the prevalence of PM [P=0.84 (OR); 0.92, 95% (Cl), 0.43-1.99]. Non-blood group O primiparae women were protected against placental malaria. This could be why some primiparae women are protected from PM, just like multiparae women.

An emerging view on vascular fibrosis molecular mediators and relevant disorders: from bench to bed.

Vascular fibrosis is a widespread pathologic condition that arises during vascular remodeling in cardiovascular dysfunctions. According to previous studies, vascular fibrosis is characterized by endothelial matrix deposition and vascular wall thickening. The RAAS and TGF-β/Smad signaling pathways have been frequently highlighted. It is, however, far from explicit in terms of understanding the cause and progression of vascular fibrosis. In this review, we collected and categorized a large number of molecules which influence the fibrosing process, in order to acquire a better understanding of vascular fibrosis, particularly of pathologic dysfunction. Furthermore, several mediators that prevent vascular fibrosis are discussed in depth in this review, with the aim that this will contribute to the future prevention and treatment of related conditions.