INTRODUCTION: Rheumatoid arthritis (RA) is associated with heightened cardiovascular disease and increased susceptibility to osteoporosis, with shared underlying mechanisms. This study aimed to investigate the association between vascular function and bone mineral density (BMD). METHODS: We conducted a cross-sectional study of 49 patients with RA at Tan Tock Seng Hospital, Singapore. Endothelial function was measured as reactive hyperaemia index (RHI)-endothelial peripheral arterial tonometry and aortic stiffness as carotid-femoral pulse wave velocity (cf-PWV) using SphygmoCor. Univariable and multivariable linear regression analyses were performed to evaluate the associations between BMD and vascular function. We used natural logarithm RHI (lnRHI) and cf-PWV as response variables, and each BMD as covariate, adjusting for body mass index, positive anti-cyclic citrullinated peptide, cumulative prednisolone dose, hydroxychloroquine use and Systematic COronary Risk Evaluation 2. RESULTS: We recruited 49 patients (mean age 61.08 ± 8.20 years), of whom 44 (89.80%) were women and 39 (81.25%) were Chinese. Significant associations were found between lnRHI and BMD at the lumbar spine (β = 0.4289, P = 0.037) and total hip (β = 0.7544, P = 0.014) in univariable analyses. Multivariable analyses confirmed these associations, showing that lower BMD at the lumbar spine (β = 0.7303, P = 0.001), femoral neck (β = 0.8694, P = 0.030) and total hip (β = 0.8909, P = 0.010) were significantly associated with worse lnRHI. No significant associations were found between BMD and cf-PWV. CONCLUSION Lower BMD is associated with endothelial dysfunction, but not aortic stiffness in patients with RA. Further longitudinal studies are needed to confirm these associations and understand the underlying mechanisms.
Humans ; Arthritis, Rheumatoid/complications* ; Female ; Male ; Bone Density ; Middle Aged ; Cross-Sectional Studies ; Vascular Stiffness ; Aged ; Singapore ; Pulse Wave Analysis ; Osteoporosis/complications* ; Endothelium, Vascular/physiopathology* ; Cardiovascular Diseases/complications* ; Carotid-Femoral Pulse Wave Velocity ; Hyperemia

Sepsis-related organ dysfunction is associated with increased morbidity and mortality. Previous studies have found that the endothelium plays crucial roles in maintaining the vascular permeability during sepsis, as well as in regulating inflammation and thrombosis. During sepsis, endothelial cells may release cytokines, chemokines, and pro-coagulant factors, as well as express adhesion molecules. In general, endothelial responses during sepsis typically inhibit bacterial transmission and coordinate leukocyte recruitment to promote bacterial clearance. However, excessive or prolonged endothelial activation can lead to impaired microcirculation, tissue hypoperfusion, and organ dysfunction. Given the structural and functional heterogeneity of endothelial cells in different organs, there are potential differences in endothelial responses by organ type, and the risk of organ damage may vary accordingly. This article reviews the endothelial response observed in sepsis and its effects on organ function, summarizes current progress in the development of therapeutic interventions targeting the endothelial response, and discusses future research directions to serve as a reference for researchers in the field.
Sepsis/complications* ; Humans ; Multiple Organ Failure/etiology* ; Endothelium, Vascular/physiopathology* ; Endothelial Cells/metabolism* ; Cytokines/metabolism* ; Animals

Atherosclerotic cardiovascular disease (ASCVD) is the deadliest disease in the world, with endothelial injury occurring throughout the course of the disease. Therefore, improvement in endothelial function is of essential importance in the prevention of ASCVD. Red yeast rice (RYR), a healthy traditional Chinese food, has a lipid modulation function and also plays a vital role in the improvement of endothelial reactivity and cardiovascular protection; thus, it is significant in the prevention and treatment of ASCVD. This article reviews the molecular mechanisms of RYR and its related products in the improvement of endothelial function in terms of endothelial reactivity, anti-apoptosis of endothelial progenitor cells, oxidative stress alleviation and anti-inflammation.
Apoptosis ; drug effects ; Atherosclerosis ; pathology ; physiopathology ; prevention & control ; Biological Products ; chemistry ; pharmacology ; therapeutic use ; Cardiovascular Diseases ; pathology ; physiopathology ; prevention & control ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; therapeutic use ; Endothelium, Vascular ; cytology ; drug effects ; physiology ; Humans ; Inflammation ; prevention & control ; Lipid Metabolism ; drug effects ; Oxidative Stress ; drug effects

The incidence and mortality rates of diabetes with cardiovascular complications are continually rising, and diabetic cardiovascular disease is becoming a major public health issue that threatens human health. Acute endothelial dysfunction and chronic cellular damage caused by diabetes are important risk factors for diabetic cardiovascular disease and related mortality. Adiponectin is an adipocyte-derived molecule with significant cytoprotective effects, including the protection against diabetes-induced vascular endothelial injury. Here we review the mechanisms of adiponectin protective effects on acute vascular endothelial dysfunction and chronic structural damage induced by diabetes.
Adiponectin ; physiology ; Cardiovascular Diseases ; complications ; Diabetes Mellitus ; pathology ; Endothelium, Vascular ; physiopathology ; Humans

Angiotensin II (Ang II) is involved in endothelium injury during the development of hypertension. Tribulus terrestris (TT) is used to treat hypertension, arteriosclerosis, and post-stroke syndrome in China. The present study aimed to determine the effects of aqueous TT extracts on endothelial injury in spontaneously hypertensive rats (SHRs) and its protective effects against Ang II-induced injury in human umbilical vein endothelial cells (HUVECs). SHRs were administered intragastrically with TT (17.2 or 8.6 g·kg·d) for 6 weeks, using valsartan (13.5 mg·kg·d) as positive control. Blood pressure, heart rate, endothelial morphology of the thoracic aorta, serum levels of Ang II, endothelin-1 (ET-1), superoxide dismutase (SOD) and malonaldehyde (MDA) were measured. The endothelial injury of HUVECs was induced by 2 × 10 mol·L Ang II. Cell Apoptosisapoptosis, intracellular reactive oxygen species (ROS) was assessed. Endothelial nitric oxide synthase (eNOS), ET-1, SOD, and MDA in the cell culture supernatant and cell migration were assayed. The expression of hypertension-linked genes and proteins were analyzed. TT decreased systolic pressure, diastolic pressure, mean arterial pressure and heart rate, improved endothelial integrity of thoracic aorta, and decreased serum leptin, Ang II, ET-1, NPY, and Hcy, while increased NO in SHRs. TT suppressed Ang II-induced HUVEC proliferation and apoptosis and prolonged the survival, and increased cell migration. TT regulated the ROS, and decreased mRNA expression of Akt1, JAK2, PI3Kα, Erk2, FAK, and NF-κB p65 and protein expression of Erk2, FAK, and NF-κB p65. In conclusion, TT demonstrated anti-hypertensive and endothelial protective effects by regulating Erk2, FAK and NF-κB p65.
Angiotensin II ; metabolism ; Animals ; Antihypertensive Agents ; administration & dosage ; Apoptosis ; drug effects ; Blood Pressure ; drug effects ; Endothelium, Vascular ; drug effects ; metabolism ; Human Umbilical Vein Endothelial Cells ; drug effects ; Humans ; Hypertension ; drug therapy ; genetics ; metabolism ; physiopathology ; Male ; NF-kappa B ; genetics ; metabolism ; Nitric Oxide Synthase Type III ; genetics ; metabolism ; Oxidative Stress ; drug effects ; Plant Extracts ; administration & dosage ; Proto-Oncogene Proteins c-akt ; genetics ; metabolism ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Reactive Oxygen Species ; metabolism ; Tribulus ; chemistry

Psoriasis is a chronic inflammatory disease involving several systems. Recent epidemiological studies show that psoriasis is closely related to erectile dysfunction (ED) and may be an independent factor of ED. Psoriasis-induced ED may be associated with vascular endothelial injury, oxidative stress, mental depression, and so on. An insight into the incidence and pathogenesis of psoriasis-related ED will help to improve psoriasis patients' early understanding of ED, prevent its development and progression, and improve the patients' quality of life.
Depression ; complications ; Endothelium, Vascular ; physiopathology ; Erectile Dysfunction ; complications ; Humans ; Incidence ; Male ; Oxidative Stress ; Psoriasis ; complications ; Quality of Life ; Risk Factors

Heart failure with preserved ejection fraction (HFPEF) is a global health problem of considerable socioeconomic burden. It is projected to worsen with the aging population worldwide. The lack of effective therapies underscores our incomplete understanding of this complex heterogeneous syndrome. A novel paradigm has recently emerged, in which central roles are ascribed to systemic inflammation and generalized endothelial dysfunction in the pathophysiology of HFPEF. In this review, we discuss the role of the endothelium in cardiovascular homeostasis and how deranged endothelial-related signaling pathways contribute to the development of HFPEF. We also review the novel therapies in various stages of research and development that target different components of this signaling pathway.
Animals ; Endothelium, Vascular/*physiopathology ; Heart Failure/diagnosis/metabolism/*physiopathology/therapy ; Humans ; Inflammation/diagnosis/metabolism/*physiopathology/therapy ; Inflammation Mediators/metabolism ; Prognosis ; Risk Factors ; Signal Transduction ; *Stroke Volume ; *Ventricular Function, Left

OBJECTIVETo investigate the role of aqueous extracts of Tribulus terrestris (TT) against oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVECs) dysfunction in vitro.

METHODSHUVECs were pre-incubated for 60 min with TT (30 and 3 μg/mL respectively) or 10(-5) mol/L valsartan (as positive controls) and then the injured endothelium model was established by applying 100 μg/mL ox-LDL for 24 h. Cell viability of HUVECs was observed by real-time cell electronic sensing assay and apoptosis rate by Annexin V/PI staining. The cell migration assay was performed with a transwell insert system. Cytoskeleton remodeling was observed by immunofluorescence assay. The content of endothelial nitric oxide synthase (eNOS) was measured by enzyme-linked immunosorbent assay. Intracellular reactive oxygen species (ROS) generation was assessed by immunofluorescence and flow cytometer. Key genes associated with the metabolism of ox-LDL were chosen for quantitative real-time polymerase chain reaction to explore the possible mechanism of TT against oxidized LDL-induced endothelial dysfunction.

RESULTSTT suppressed ox-LDL-induced HUVEC proliferation and apoptosis rates significantly (41.1% and 43.5% after treatment for 3 and 38 h, respectively; P<0.05). It also prolonged the HUVEC survival time and postponed the cell's decaying stage (from the 69th h to over 100 h). According to the immunofluorescence and transwell insert system assay, TT improved the endothelial cytoskeletal network, and vinculin expression and increased cell migration. Additionally, TT regulated of the synthesis of endothelial nitric oxide synthase and generation of intracellular reactive oxygen species (P<0.05). Both 30 and 3 μg/mL TT demonstrated similar efficacy to valsartan. TT normalized the increased mRNA expression of PI3Kα and Socs3. It also decreased mRNA expression of Akt1, AMPKα1, JAK2, LepR and STAT3 induced by ox-LDL. The most notable changes were JAK2, LepR, PI3Kα, Socs3 and STAT3.

CONCLUSIONSTT demonstrated potential lowering lipid benefits, anti-hypertension and endothelial protective effects. It also suggested that the JAK2/STAT3 and/or PI3K/AKT pathway might be a very important pathway which was involved in the pharmacological mechanism of TT as the vascular protective agent.

Apoptosis ; drug effects ; Cell Movement ; drug effects ; Cell Survival ; drug effects ; Cytoskeleton ; drug effects ; metabolism ; Endothelium, Vascular ; drug effects ; pathology ; physiopathology ; Enzyme-Linked Immunosorbent Assay ; Fluorescent Antibody Technique ; Gene Expression Regulation ; drug effects ; Human Umbilical Vein Endothelial Cells ; drug effects ; Humans ; Lipoproteins, LDL ; adverse effects ; Nitric Oxide Synthase Type III ; metabolism ; Plant Extracts ; pharmacology ; Protective Agents ; pharmacology ; Reactive Oxygen Species ; metabolism ; Tribulus ; chemistry ; Vinculin ; metabolism ; Water ; chemistry

PURPOSE: Endothelial dysfunction (ED) is a pivotal phenomenon in the development of cardiovascular disease (CVD) in patients receiving hemodialysis (HD). Indoxyl sulfate (IS) is a known uremic toxin that induces ED in patients with chronic kidney disease. The aim of this study was to investigate whether AST-120, an absorbent of IS, improves microvascular or macrovascular ED in HD patients. MATERIALS AND METHODS: We conducted a prospective, case-controlled trial. Fourteen patients each were enrolled in respective AST-120 and control groups. The subjects in the AST-120 group were treated with AST-120 (6 g/day) for 6 months. Microvascular function was assessed by laser Doppler flowmetry using iontophoresis of acetylcholine (Ach) and sodium nitroprusside (SNP) at baseline and again at 3 and 6 months. Carotid arterial intima-media thickness (cIMT) and flow-mediated vasodilation were measured at baseline and 6 months. The Wilcoxon rank test was used to compare values before and after AST-120 treatment. RESULTS: Ach-induced iontophoresis (endothelium-dependent response) was dramatically ameliorated at 3 months and 6 months in the AST-120 group. SNP-induced response showed delayed improvement only at 6 months in the AST-120 group. The IS level was decreased at 3 months in the AST-120 group, but remained stable thereafter. cIMT was significantly reduced after AST-120 treatment. No significant complications in patients taking AST-120 were reported. CONCLUSION: AST-120 ameliorated microvascular ED and cIMT in HD patients. A randomized study including a larger population will be required to establish a definitive role of AST-120 as a preventive medication for CVD in HD patients.
Acetylcholine ; Adult ; Carbon/*therapeutic use ; Cardiovascular Diseases/etiology/*prevention & control ; Carotid Intima-Media Thickness ; Endothelium, Vascular/*physiopathology ; Female ; Humans ; Iontophoresis ; Kidney Failure, Chronic/complications/*physiopathology/*therapy ; Laser-Doppler Flowmetry ; Male ; Microcirculation/physiology ; Middle Aged ; Nitroprusside ; Oxides/*therapeutic use ; Prospective Studies ; *Renal Dialysis ; Young Adult

OBJECTIVETo assess the relationship between visit-to-visit blood pressure (BP) variability (BPV) and vascular endothelial function in a cohort of elderly hypertensive patients.

METHODSA total of 174 elderly patients with essential hypertension were included in the study. The participants had their office BP measured during the 12-month follow-up. Right brachial artery diameter was assessed at rest, during reactive hyperemia (flow-mediated dilation, FMD), and after nitroglycerin administration (nitroglycerin-mediated dilation, NMD). The participants were divided into two groups according to FMD% or FMD/NMD ratio. The correlations between BPV and endothelial function were analyzed by univariate analysis and multiple linear regression analysis.

RESULTSThe participants classified as having a decreased endothelial function according to FMD/NMD ratio had significantly lower FMD% and higher BPV and NMD% (P<0.05). The percentage of CCBs use in normal endothelial function group was significantly higher than that in decreased endothelial function group (79.55% vs 63.95%, P<0.05). Multiple linear regression analysis revealed a significant negative association between FMD/NMD ratio and BPV, and this association remained significant after adjustment for age, body mass index, and mean BP levels.

CONCLUSIONSFMD/NMD ratio is a better marker of endothelial function than FMD, and an increased visit-to-visit variability of BP is associated with a decreased endothelial function.

Aged ; Blood Pressure ; Brachial Artery ; Endothelium, Vascular ; physiopathology ; Essential Hypertension ; Humans ; Hypertension ; Multivariate Analysis ; Nitroglycerin ; Regression Analysis ; Vasodilation