scholarly journals Small GTPases and Their Role in Vascular Disease

2019 ◽  
Vol 20 (4) ◽  
pp. 917 ◽  
Author(s):  
Alison Flentje ◽  
Richa Kalsi ◽  
Thomas Monahan
Keyword(s):  
Cardiovascular Disease ◽  
Endothelial Cells ◽  
Blood Vessel ◽  
Vascular Disease ◽  
The United States ◽  
Small Gtpases ◽  
Endothelial Cell Migration ◽  
Open Reconstruction ◽  
End Stage

Over eighty million people in the United States have cardiovascular disease that can affect the heart causing myocardial infarction; the carotid arteries causing stroke; and the lower extremities leading to amputation. The treatment for end-stage cardiovascular disease is surgical—either endovascular therapy with balloons and stents—or open reconstruction to reestablish blood flow. All interventions damage or destroy the protective inner lining of the blood vessel—the endothelium. An intact endothelium is essential to provide a protective; antithrombotic lining of a blood vessel. Currently; there are no agents used in the clinical setting that promote reendothelialization. This process requires migration of endothelial cells to the denuded vessel; proliferation of endothelial cells on the denuded vessel surface; and the reconstitution of the tight adherence junctions responsible for the formation of an impermeable surface. These processes are all regulated in part and are dependent on small GTPases. As important as the small GTPases are for reendothelialization, dysregulation of these molecules can result in various vascular pathologies including aneurysm formation, atherosclerosis, diabetes, angiogenesis, and hypertension. A better understanding of the role of small GTPases in endothelial cell migration is essential to the development for novel agents to treat vascular disease.

scholarly journals Emerging Role of AP-1 Transcription Factor JunB in Angiogenesis and Vascular Development

2021 ◽  
Vol 22 (6) ◽  
pp. 2804
Author(s):  
Yasuo Yoshitomi ◽  
Takayuki Ikeda ◽  
Hidehito Saito-Takatsuji ◽  
Hideto Yonekura
Keyword(s):  
Endothelial Cells ◽  
Transcription Factor ◽  
Blood Vessel ◽  
Vascular Endothelial Cells ◽  
Vascular Development ◽  
Endothelial Cell Migration ◽  
Vascular Endothelial ◽  
Blood Vessel Formation ◽  
Vessel Formation

Blood vessels are essential for the formation and maintenance of almost all functional tissues. They play fundamental roles in the supply of oxygen and nutrition, as well as development and morphogenesis. Vascular endothelial cells are the main factor in blood vessel formation. Recently, research findings showed heterogeneity in vascular endothelial cells in different tissue/organs. Endothelial cells alter their gene expressions depending on their cell fate or angiogenic states of vascular development in normal and pathological processes. Studies on gene regulation in endothelial cells demonstrated that the activator protein 1 (AP-1) transcription factors are implicated in angiogenesis and vascular development. In particular, it has been revealed that JunB (a member of the AP-1 transcription factor family) is transiently induced in endothelial cells at the angiogenic frontier and controls them on tip cells specification during vascular development. Moreover, JunB plays a role in tissue-specific vascular maturation processes during neurovascular interaction in mouse embryonic skin and retina vasculatures. Thus, JunB appears to be a new angiogenic factor that induces endothelial cell migration and sprouting particularly in neurovascular interaction during vascular development. In this review, we discuss the recently identified role of JunB in endothelial cells and blood vessel formation.

Reactive oxygen species mediate Rac-induced loss of cell-cell adhesion in primary human endothelial cells

2002 ◽  
Vol 115 (9) ◽  
pp. 1837-1846 ◽  
Author(s):  
Sandra van Wetering ◽  
Jaap D. van Buul ◽  
Safira Quik ◽  
Frederik P. J. Mul ◽  
Eloise C. Anthony ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Cell Migration ◽  
Cell Adhesion ◽  
Endothelial Cell ◽  
Reactive Oxygen ◽  
Small Gtpases ◽  
Endothelial Cell Migration ◽  
Oxygen Species ◽  
Cell Cell

The integrity of the endothelium is dependent on cell-cell adhesion, which is mediated by vascular-endothelial (VE)-cadherin. Proper VE-cadherin-mediated homotypic adhesion is, in turn, dependent on the connection between VE-cadherin and the cortical actin cytoskeleton. Rho-like small GTPases are key molecular switches that control cytoskeletal dynamics and cadherin function in epithelial as well as endothelial cells. We show here that a cell-penetrating, constitutively active form of Rac (Tat-RacV12) induces a rapid loss of VE-cadherin-mediated cell-cell adhesion in endothelial cells from primary human umbilical veins (pHUVEC). This effect is accompanied by the formation of actin stress fibers and is dependent on Rho activity. However,transduction of pHUVEC with Tat-RhoV14, which induces pronounced stress fiber and focal adhesion formation, did not result in a redistribution of VE-cadherin or an overall loss of cell-cell adhesion. In line with this observation, endothelial permeability was more efficiently increased by Tat-RacV12 than by Tat-RhoV14. The loss of cell-cell adhesion, which is induced by Tat-RacV12, occurred in parallel to and was dependent upon the intracellular production of reactive oxygen species (ROS). Moreover, Tat-RacV12 induced an increase in tyrosine phosphorylation of a component the VE-cadherin-catenin complex, which was identified as α-catenin. The functional relevance of this signaling pathway was further underscored by the observation that endothelial cell migration, which requires a transient reduction of cell-cell adhesion, was blocked when signaling through ROS was inhibited. In conclusion, Rac-mediated production of ROS represents a previously unrecognized means of regulating VE-cadherin function and may play an important role in the (patho)physiology associated with inflammation and endothelial damage as well as with endothelial cell migration and angiogenesis.

scholarly journals Mitochondrial Function, Biology, and Role in Disease

2016 ◽  
Vol 118 (12) ◽  
pp. 1960-1991 ◽  
Author(s):  
Elizabeth Murphy ◽  
Hossein Ardehali ◽  
Robert S. Balaban ◽  
Fabio DiLisa ◽  
Gerald W. Dorn ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Mitochondrial Function ◽  
The United States ◽  
Therapeutic Interventions ◽  
Therapeutic Approaches ◽  
Mitochondrial Defects ◽  
Exciting Time ◽  
Insight Into ◽  
Novel Therapeutic

Cardiovascular disease is a major leading cause of morbidity and mortality in the United States and elsewhere. Alterations in mitochondrial function are increasingly being recognized as a contributing factor in myocardial infarction and in patients presenting with cardiomyopathy. Recent understanding of the complex interaction of the mitochondria in regulating metabolism and cell death can provide novel insight and therapeutic targets. The purpose of this statement is to better define the potential role of mitochondria in the genesis of cardiovascular disease such as ischemia and heart failure. To accomplish this, we will define the key mitochondrial processes that play a role in cardiovascular disease that are potential targets for novel therapeutic interventions. This is an exciting time in mitochondrial research. The past decade has provided novel insight into the role of mitochondria function and their importance in complex diseases. This statement will define the key roles that mitochondria play in cardiovascular physiology and disease and provide insight into how mitochondrial defects can contribute to cardiovascular disease; it will also discuss potential biomarkers of mitochondrial disease and suggest potential novel therapeutic approaches.

Acid–Base Disturbances

2014 ◽  
pp. 594-602
Author(s):  
Julian L. Seifter
Keyword(s):  
United States ◽  
Cardiovascular Disease ◽  
Peritoneal Dialysis ◽  
Renal Transplantation ◽  
End Stage Renal Disease ◽  
The United States ◽  
Cardiovascular Complications ◽  
Diabetic Patients ◽  
Stage Renal Disease ◽  
End Stage

According to projections from the United States Renal Data Service (USRDS), 〉600,000 individuals in the United States will have end-stage renal disease (ESRD) by 2010. The leading cause of ESRD in the United State is diabetes, followed by hypertension. As the care of diabetic patients has improved, particularly in the area of cardiovascular disease, they are living through their cardiovascular complications long enough to develop ESRD. As a consequence, since the inception of the Medicare ESRD program. the dialysis population has gradually become older with increasing numbers of comorbid conditions. Renal replacement therapy in the form of hemodialysis or peritoneal dialysis may serve as a bridge to the best form of renal replacement, renal transplantation. The demand for suitable kidneys for transplantation far exceeds the supply, leaving many patients on dialysis for extended periods of time.

scholarly journals Obesity and Cancer: 27-Hydroxycholesterol, the Missing Link

2020 ◽  
Vol 21 (14) ◽  
pp. 4822
Author(s):  
Arvand Asghari ◽  
Michihisa Umetani
Keyword(s):  
United States ◽  
Cardiovascular Disease ◽  
Estrogen Receptor ◽  
Risk Factor ◽  
Cause Of Death ◽  
The United States ◽  
Missing Link ◽  
Receptor Modulator ◽  
Obesity And Cancer

Obesity is currently affecting more than 40% of the Americans, and if it progresses with this rate, soon one out of two Americans will be obese. Obesity is an important risk factor for several disorders including cardiovascular disease, the first cause of death in the United States. Cancer follows as the second deadliest disease, and a link between obesity and cancer has been suggested. However, it is very hard to establish an exact connection between obesity and cancers due to the multifactorial nature of obesity. Hypercholesterolemia is a comorbidity of obesity and also linked to several cancers. Recently a cholesterol metabolite 27-hydroxycholesterol (27HC) was found to be an endogenous selective estrogen receptor modulator (SERM), which opened new doors toward several interesting studies on the role of this molecule in biological disorders. It is speculated that 27HC might be the missing link in the obesity and cancer chain. Here, we explored the effects of 27-hydroxycholesterol on obesity and cancers with a focus on the SERM capacity of 27HC.

scholarly journals Role of Berry Anthocyanins and Phenolic Acids on Cell Migration and Angiogenesis: An Updated Overview

Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 1075 ◽  
Author(s):  
Panagiotis Tsakiroglou ◽  
Natalie E. VandenAkker ◽  
Cristian Del Bo’ ◽  
Patrizia Riso ◽  
Dorothy Klimis-Zacas
Keyword(s):  
Wound Healing ◽  
Cell Migration ◽  
Phenolic Acids ◽  
Rho Gtpase ◽  
Small Gtpases ◽  
Endothelial Cell Migration ◽  
Berry Extracts

Cell migration is a critical process that is highly involved with normal and pathological conditions such as angiogenesis and wound healing. Important members of the RHO GTPase family are capable of controlling cytoskeleton conformation and altering motility characteristics of cells. There is a well-known relationship between small GTPases and the PI3K/AKT pathway. Endothelial cell migration can lead to angiogenesis, which is highly linked to wound healing processes. Phenolics, flavonoids, and anthocyanins are major groups of phytochemicals and are abundant in many natural products. Their antioxidant, antimicrobial, anti-inflammatory, antidiabetic, angiogenenic, neuroprotective, hepatoprotective, and cardioprotective properties have been extensively documented. This comprehensive review focuses on the in vitro and in vivo role of berry extracts and single anthocyanin and phenolic acid compounds on cell migration and angiogenesis. We aim to summarize the most recent published studies focusing on the experimental model, type of berry extract, source, dose/concentration and overall effect(s) of berry extracts, anthocyanins, and phenolic acids on the above processes.

scholarly journals Vasculogenesis and Angiogenesis: Molecular and Cellular Controls

2003 ◽  
Vol 9 (3) ◽  
pp. 239-248 ◽  
Author(s):  
N. Kubis ◽  
B.I. Levy
Keyword(s):  
Endothelial Cells ◽  
Growth Factors ◽  
Endothelial Cell Migration ◽  
Angiogenic Growth Factors ◽  
Blood Vessel Formation ◽  
Vasculogenesis And Angiogenesis ◽  
Cell Migration And Proliferation ◽  
Extracellular Proteolysis ◽  
Coagulation And Fibrinolysis

Angiogenesis, defined as a new blood vessel formation from a pre-existing vessel, is initiated by angiogenic growth factors and their receptors that induce endothelial cell migration and proliferation. Extracellular proteolysis is essential for deassembly and reassembly of endothelial cells to their environmental matrix. The aim of this review is to update data on the role of the coagulation and fibrinolysis system, metalloproteinases and adhesion molecules during this step of angiogenesis.

Lipids and cardiovascular disease: where does dietary intervention sit alongside statin therapy?

2016 ◽  
Vol 7 (6) ◽  
pp. 2603-2614 ◽  
Author(s):  
Ian L. Megson ◽  
Phillip D. Whitfield ◽  
Ioannis Zabetakis
Keyword(s):  
Cardiovascular Disease ◽  
Blood Vessel ◽  
Statin Therapy ◽  
Dietary Intervention ◽  
Vessel Walls

The role of lipids at the onset of atherosclerosis in blood vessel walls.

Eicosanoid regulation of angiogenesis: role of endothelial arachidonate 12-lipoxygenase

Blood ◽  
2000 ◽  
Vol 95 (7) ◽  
pp. 2304-2311
Author(s):  
Daotai Nie ◽  
Keqin Tang ◽  
Clement Diglio ◽  
Kenneth V. Honn
Keyword(s):  
Endothelial Cells ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Cell Line ◽  
Critical Role ◽  
Endothelial Cell Migration ◽  
Vascular Endothelial ◽  
12 Lipoxygenase

Angiogenesis, the formation of new capillaries from preexisting blood vessels, is a multistep, highly orchestrated process involving vessel sprouting, endothelial cell migration, proliferation, tube differentiation, and survival. Eicosanoids, arachidonic acid (AA)-derived metabolites, have potent biologic activities on vascular endothelial cells. Endothelial cells can synthesize various eicosanoids, including the 12-lipoxygenase (LOX) product 12(S)-hydroxyeicosatetraenoic acid (HETE). Here we demonstrate that endogenous 12-LOX is involved in endothelial cell angiogenic responses. First, the 12-LOX inhibitor, N-benzyl-N-hydroxy-5-phenylpentanamide (BHPP), reduced endothelial cell proliferation stimulated either by basic fibroblast growth factor (bFGF) or by vascular endothelial growth factor (VEGF). Second, 12-LOX inhibitors blocked VEGF-induced endothelial cell migration, and this blockage could be partially reversed by the addition of 12(S)-HETE. Third, pretreatment of an angiogenic endothelial cell line, RV-ECT, with BHPP significantly inhibited the formation of tubelike/cordlike structures within Matrigel. Fourth, overexpression of 12-LOX in the CD4 endothelial cell line significantly stimulated cell migration and tube differentiation. In agreement with the critical role of 12-LOX in endothelial cell angiogenic responses in vitro, the 12-LOX inhibitor BHPP significantly reduced bFGF-induced angiogenesis in vivo using a Matrigel implantation bioassay. These findings demonstrate that AA metabolism in endothelial cells, especially the 12-LOX pathway, plays a critical role in angiogenesis.

The role of renal anemia and cardiovascular disease in the progression of chronic glomerulonephritis

2016 ◽  
Vol 88 (12) ◽  
pp. 57-61 ◽  
Author(s):  
I T Murkamilov ◽  
I G Gordeev ◽  
R R Kaliev
Keyword(s):  
Cardiovascular Disease ◽  
Disease Onset ◽  
Hemoglobin Concentration ◽  
Chronic Glomerulonephritis ◽  
Bicycle Ergometry ◽  
Reactive Protein ◽  
Persistent Proteinuria ◽  
Cell Counts ◽  
End Stage

Aim. To study the rate of chronic glomerulonephritis progression when added by anemia and cardiovascular disease (CVD). Subjects and methods. 231 patients (133 men and 98 women) with predialysis chronic glomerulonephritis (CGN) were examined. The patients’ mean age of was 35.8±11.8 years; the disease duration was 1 to 17 years. The disease onset was the date when urinalysis showed evidence of persistent proteinuria and (or) hematuria. Besides, the time when anemia developed and the clinical and instrumental signs of CVD appeared was taken as the initial reference point; the time when end-stage renal failure was diagnosed was taken to be the endpoint. Red blood cell counts with the inclusion of its indices, hemoglobin concentration, hematocrit values, daily proteinuria values, and glomerular filtration rate were analyzed. The biochemical parameters included the concentrations of electrolytes, creatinine, fibrinogen, iron, cholesterol, total protein and C-reactive protein (CRP). Electrocardiography and echocardiography, bicycle ergometry and 24-hour ECG monitoring were used to detect CVD. Results. The presence of anemia and CVD in patients with predialysis CGN versus those without anemia and CVD was associated with an increase in the concentrations of CRP [36.2 and 12.6%; respectively; (p

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