Mechanobiology of Endothelial Cells Related to the Formation of Arterial Disease

2016 ◽  
pp. 141-157 ◽  
Author(s):  
Noriyuki Kataoka
Keyword(s):  
Endothelial Cells ◽  
Arterial Disease

scholarly journals Analyses of the pericyte transcriptome in ischemic skeletal muscles

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yuan-chi Teng ◽  
Alfredo Leonardo Porfírio-Sousa ◽  
Giulia Magri Ribeiro ◽  
Marcela Corso Arend ◽  
Lindolfo da Silva Meirelles ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Limb Ischemia ◽  
Inflammatory Cells ◽  
Cell Types ◽  
Arterial Disease ◽  
The Body ◽  
Time Points

Abstract Background Peripheral arterial disease (PAD) affects millions of people and compromises quality of life. Critical limb ischemia (CLI), which is the most advanced stage of PAD, can cause nonhealing ulcers and strong chronic pain, and it shortens the patients’ life expectancy. Cell-based angiogenic therapies are becoming a real therapeutic approach to treat CLI. Pericytes are cells that surround vascular endothelial cells to reinforce vessel integrity and regulate local blood pressure and metabolism. In the past decade, researchers also found that pericytes may function as stem or progenitor cells in the body, showing the potential to differentiate into several cell types. We investigated the gene expression profiles of pericytes during the early stages of limb ischemia, as well as the alterations in pericyte subpopulations to better understand the behavior of pericytes under ischemic conditions. Methods In this study, we used a hindlimb ischemia model to mimic CLI in C57/BL6 mice and explore the role of pericytes in regeneration. To this end, muscle pericytes were isolated at different time points after the induction of ischemia. The phenotypes and transcriptomic profiles of the pericytes isolated at these discrete time points were assessed using flow cytometry and RNA sequencing. Results Ischemia triggered proliferation and migration and upregulated the expression of myogenesis-related transcripts in pericytes. Furthermore, the transcriptomic analysis also revealed that pericytes induce or upregulate the expression of a number of cytokines with effects on endothelial cells, leukocyte chemoattraction, or the activation of inflammatory cells. Conclusions Our findings provide a database that will improve our understanding of skeletal muscle pericyte biology under ischemic conditions, which may be useful for the development of novel pericyte-based cell and gene therapies.

Abstract 3321: Gender Impacts Capillary Density and Skeletal Muscle Composition in Patients With Peripheral Arterial Disease

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
William S Jones ◽  
Brian D Duscha ◽  
Jennifer L Robbins ◽  
Amy J Aldrich ◽  
Judy G Regensteiner ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Gender Differences ◽  
Endothelial Cells ◽  
Muscle Fiber ◽  
Fiber Type ◽  
Capillary Density ◽  
Arterial Disease ◽  
Healthy Controls ◽  
Muscle Composition ◽  
Peripheral Arterial

Background : Peripheral arterial disease (PAD) is a disorder characterized by impaired blood flow to the legs and maladaptive changes in the skeletal muscle. It is generally accepted that the skeletal muscle characteristics in patients with PAD include decreased capillary density and an altered percentage of oxidative myofibers. The scientific literature is conflicting, and it is based on studies with small sample size and older methodologies of skeletal muscle analysis. In addition, women are under-represented or not included at all in these studies. Hypothesis : We hypothesized that there would be differences in skeletal muscle composition in PAD patients compared to healthy controls. We further hypothesized that there would be gender differences in skeletal muscle composition in PAD patients versus healthy controls. Methods : Thirty -one patients with PAD and 31 age-, gender-, and activity-matched healthy controls underwent gastrocnemius muscle biopsy. Capillary density analysis and muscle fiber type determination were performed using immunohistochemistry techniques. Capillary density was measured as endothelial cells per muscle fiber and endothelial cells per area (mm 2 ). Results : There was no significant difference in capillary density in patients with PAD versus healthy controls when measured as endothelial cells per fiber (mean = 1.45 ± 0.43 vs. 1.50 ± 0.35, NS) or area (mean = 1.20 ± 0.29 vs. 1.29 ± 0.33, NS). There was also no difference in muscle fiber type composition between the groups. In the PAD cohort, capillary density was significantly lower in the men versus the women (mean = 1.36 ± 0.35 vs. 1.59 ± 0.51, p=0.005). In our cohort of women, there was no difference in capillary density in patients with PAD versus healthy controls (N=12). In men, capillary density was significantly lower in the PAD group versus healthy controls (N=19, mean = 1.09 ± 0.20 vs. 1.28 ± 0.34, p=0.043). Conclusions : Our data fail to confirm the belief that patients with PAD have a decreased capillary density and an altered percentage of oxidative myofibers. However, we did find that gender has an important impact on these characteristics. Further study of skeletal muscle composition in PAD may help to better understand the functional relevance of the gender differences.

Abstract 53: Ablation of Thrombin Signaling in Platelets but Not in Endothelial Cells Impairs Hemostasis in a Mouse Model of Spontaneous Gastrointestinal Bleeding

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Stephen J Wilson ◽  
Maria M Stevens ◽  
Shaun R Coughlin
Keyword(s):  
Myocardial Infarction ◽  
Endothelial Cells ◽  
Platelet Activation ◽  
Bleeding Risk ◽  
Arterial Disease ◽  
Gi Bleeding ◽  
Intestinal Polyposis ◽  
Wild Type ◽  
Spontaneous Bleeding ◽  
Peripheral Arterial

Human PAR1 is expressed in endothelial cells as well as in platelets where it facilitates the response to thrombin and platelet activation. Vorapaxar, a PAR1 antagonist, prevents myocardial infarction and stroke in patients with prior MI or peripheral arterial disease at a cost of increased bleeding risk. Par1 is also highly expressed in endothelial cells in mice, and Par1-deficiency is associated with bleeding in the mouse embryo at midgestation. Additionally, known actions of endothelial PAR1 activation suggest pro-hemostatic functions. This raises the question of whether inhibition of PAR1 function in endothelial cells (in addition to PAR1 inhibition in platelets) contributes to the bleeding risk associated with Vorapaxar treatment. Our previous work demonstrated that Par1 deficiency results in loss of thrombin signaling in mouse endothelial cells but not mouse platelets, while Par4 deficiency ablated thrombin-induced platelet activation in mice. Thus, mice allow us to separate loss of thrombin signaling in platelets from loss of thrombin signaling in endothelial cells. Accordingly, we used Apc min/+ mice, which develop intestinal polyposis and spontaneous GI bleeding, as a model to determine whether loss of thrombin signaling in platelets (Par4 KO) or endothelial and other cells (Par1 KO) exacerbates spontaneous bleeding. Hematocrit and other hematologic parameters were measured biweekly from 7 weeks through 15 weeks of age. Hematocrits in mice wild-type for Apc were stable over this period (41.48 ± 0.48 at 7 weeks; 40.48 ± 0.37 at 15 weeks, n=15). Hematocrits in Apc min/+ mice fell approximately linearly from 37.06 ± 0.82 at 7 weeks to 14.39 ± 1.12 at 15 weeks (n=15). Hematocrits in Par1-deficient Apc min/+ mice were indistinguishable from those in Apc min/+ without Par deficiency (14.39 ± 1.12 vs 14.47 ± 1.66 at 15 weeks; n=6-15). By contrast, Par4-deficient Apc min/+ mice were already severely anemic at 7 weeks compared to Apc min/+ mice (19 ± 2.0 vs 39 ± 3.6; p<0.01, n=4). Par-dependent differences in polyp count and size were not detected. Taken together, our results suggest that loss of thrombin signaling in platelets promotes spontaneous GI bleeding in the Apc min model while loss of thrombin signaling in endothelial cells is without effect in this system.

scholarly journals MicroRNA-133a impairs perfusion recovery after hindlimb ischemia in diabetic mice

2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Lingdan Chen ◽  
Chunli Liu ◽  
Dejun Sun ◽  
Tao Wang ◽  
Li Zhao ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Endothelial Cells ◽  
Arterial Disease ◽  
Tube Formation ◽  
Cgmp Level ◽  
Diabetic Mice ◽  
Rt Pcr ◽  
Patients With Diabetes ◽  
Peripheral Arterial ◽  
Ischemic Muscle

Objective: Peripheral arterial disease (PAD) patients with diabetes mellitus suffer from impaired neovascularization after ischemia which results in poorer outcomes. MicroRNA (miR)-133a is excessively expressed in endothelial cells under diabetic conditions. Here, we test whether diabetes-induced miR-133a up-regulation is involved in the impaired capability of neovascularization in experimental PAD models. Methods and results: MiR-133a level was measured by quantitative RT-PCR and showed a higher expression level in the ischemic muscle from diabetic mice when compared with nondiabetic mice. Knockdown of miR-133a using antagomir improved perfusion recovery and angiogenesis in experimental PAD model with diabetes day 21 after HLI. On the other hand, overexpression of miR-133a impaired perfusion recovery. Ischemic muscle was harvested day 7 after experimental PAD for biochemical test, miR-133a antagonism resulted in reduced malondialdehyde, and it increased GTP cyclohydrolase 1 (GCH1), and cyclic guanine monophosphate (cGMP) levels. In cultured endothelial cells, miR-133a antagonism resulted in reduced reactive oxygen species level, and it increased tube formation, nitric oxide (NO), and cGMP level. Moreover, miR-133a antagonism-induced angiogenesis was abolished by GCH1 inhibitor. In contrary, miR-133a overexpression impairs angiogenesis and it reduces GCH1, NO, and cGMP levels in nondiabetic models. Conclusion: Diabetes mellitus-induced miR-133a up-regulation impairs angiogenesis in PAD by reducing NO synthesis in endothelial cells. MiR-133a antagonism improves postischemic angiogenesis.

scholarly journals Reversibility of endothelial dysfunction in diabetes: role of polyphenols

2016 ◽  
Vol 116 (2) ◽  
pp. 223-246 ◽  
Author(s):  
N. Suganya ◽  
E. Bhakkiyalakshmi ◽  
D. V. L. Sarada ◽  
K. M. Ramkumar
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Vessel Wall ◽  
Molecular Mechanisms ◽  
Vascular System ◽  
Microvascular Complications ◽  
Arterial Disease ◽  
Cellular Adhesion ◽  
Vascular Homeostasis

AbstractThe endothelium, a thin single sheet of endothelial cells, is a metabolically active layer that coats the inner surface of blood vessels and acts as an interface between the circulating blood and the vessel wall. The endothelium through the secretion of vasodilators and vasoconstrictors serves as a critical mediator of vascular homeostasis. During the development of the vascular system, it regulates cellular adhesion and vessel wall inflammation in addition to maintaining vasculogenesis and angiogenesis. A shift in the functions of the endothelium towards vasoconstriction, proinflammatory and prothrombic states characterise improper functioning of these cells, leading to endothelial dysfunction (ED), implicated in the pathogenesis of many diseases including diabetes. Major mechanisms of ED include the down-regulation of endothelial nitric oxide synthase levels, differential expression of vascular endothelial growth factor, endoplasmic reticulum stress, inflammatory pathways and oxidative stress. ED tends to be the initial event in macrovascular complications such as coronary artery disease, peripheral arterial disease, stroke and microvascular complications such as nephropathy, neuropathy and retinopathy. Numerous strategies have been developed to protect endothelial cells against various stimuli, of which the role of polyphenolic compounds in modulating the differentially regulated pathways and thus maintaining vascular homeostasis has been proven to be beneficial. This review addresses the factors stimulating ED in diabetes and the molecular mechanisms of natural polyphenol antioxidants in maintaining vascular homeostasis.

scholarly journals Induced endothelial cells from peripheral arterial disease patients and neonatal fibroblasts have comparable angiogenic properties

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255075
Author(s):  
Jack D. Hywood ◽  
Sara Sadeghipour ◽  
Zoe E. Clayton ◽  
Jun Yuan ◽  
Colleen Stubbs ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Peripheral Arterial Disease ◽  
Murine Model ◽  
Arterial Disease ◽  
Scid Mice ◽  
Laser Doppler ◽  
Cytokine Secretion ◽  
Endothelial Phenotype ◽  
Peripheral Arterial

Induced endothelial cells (iECs) generated from neonatal fibroblasts via transdifferentiation have been shown to have pro-angiogenic properties and are a potential therapy for peripheral arterial disease (PAD). It is unknown if iECs can be generated from fibroblasts collected from PAD patients and whether these cells are pro-angiogenic. In this study fibroblasts were collected from four PAD patients undergoing carotid endarterectomies. These cells, and neonatal fibroblasts, were transdifferentiated into iECs using modified mRNA. Endothelial phenotype and pro-angiogenic cytokine secretion were investigated. NOD-SCID mice underwent surgery to induce hindlimb ischaemia in a murine model of PAD. Mice received intramuscular injections with either control vehicle, or 1 × 106 neonatal-derived or 1 × 106 patient-derived iECs. Recovery in perfusion to the affected limb was measured using laser Doppler scanning. Perfusion recovery was enhanced in mice treated with neonatal-derived iECs and in two of the three patient-derived iEC lines investigated in vivo. Patient-derived iECs can be successfully generated from PAD patients and for specific patients display comparable pro-angiogenic properties to neonatal-derived iECs.

scholarly journals Cell Type Dependent Suppression of Inflammatory Mediators by Myocardin Related Transcription Factors

2021 ◽  
Vol 12 ◽  
Author(s):  
Li Liu ◽  
Elisabeth Bankell ◽  
Catarina Rippe ◽  
Björn Morén ◽  
Karin G. Stenkula ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Transcription Factors ◽  
Vascular Inflammation ◽  
Arterial Disease ◽  
Suppressive Effect ◽  
Cell Type ◽  
Human Coronary Artery ◽  
Anti Inflammatory ◽  
The Impact

Myocardin related transcription factors (MRTFs: MYOCD/myocardin, MRTF-A, and MRTF-B) play a key role in smooth muscle cell differentiation by activating contractile genes. In atherosclerosis, MRTF levels change, and most notable is a fall of MYOCD. Previous work described anti-inflammatory properties of MRTF-A and MYOCD, occurring through RelA binding, suggesting that MYOCD reduction could contribute to vascular inflammation. Recent studies have muddled this picture showing that MRTFs may show both anti- and pro-inflammatory properties, but the basis of these discrepancies remain unclear. Moreover, the impact of MRTFs on inflammatory signaling pathways in tissues relevant to human arterial disease is uncertain. The current work aimed to address these issues. RNA-sequencing after forced expression of myocardin in human coronary artery smooth muscle cells (hCASMCs) showed reduction of pro-inflammatory transcripts, including CCL2, CXCL8, IL6, and IL1B. Side-by-side comparison of MYOCD, MRTF-A, and MRTF-B in hCASMCs, showed that the anti-inflammatory impact was shared among MRTFs. Correlation analyses using human arterial transcriptomic datasets revealed negative correlations between MYOCD, MRTFA, and SRF, on the one hand, and the inflammatory transcripts, on the other. A pro-inflammatory drive from lipopolysaccharide, did not change the size of the suppressive effect of MRTF-A in hCASMCs on either mRNA or protein levels. To examine cell type-dependence, we compared the anti-inflammatory impact in hCASMCs, with that in human bladder SMCs, in endothelial cells, and in monocytes (THP-1 cells). Surprisingly, little anti-inflammatory activity was seen in endothelial cells and monocytes, and in bladder SMCs, MRTF-A was pro-inflammatory. CXCL8, IL6, and IL1B were increased by the MRTF-SRF inhibitor CCG-1423 and by MRTF-A silencing in hCASMCs, but depolymerization of actin, known to inhibit MRTF activity, had no stimulatory effect, an exception being IL1B. Co-immunoprecipitation supported binding of MRTF-A to RelA, supporting sequestration of this important pro-inflammatory mediator as a mechanism. Dexamethasone treatment and silencing of RelA (by 76 ± 1%) however only eliminated a fraction of the MRTF-A effect (≈25%), suggesting mechanisms beyond RelA binding. Indeed, SRF silencing suggested that MRTF-A suppression of IL1B and CXCL8 depends on SRF. This work thus supports an anti-inflammatory impact of MRTF-SRF signaling in hCASMCs and in intact human arteries, but not in several other cell types.

Vascular Surgery

2020 ◽  
pp. 277-290
Author(s):  
Jad M. Abdelsattar ◽  
Moustafa M. El Khatib ◽  
T. K. Pandian ◽  
Samuel J. Allen ◽  
David R. Farley
Keyword(s):  
Myocardial Infarction ◽  
Endothelial Cells ◽  
Blood Vessel ◽  
Vascular Surgery ◽  
Ct Angiography ◽  
Heart Attack ◽  
Vessel Wall ◽  
Vascular Diseases ◽  
Arterial Disease ◽  
Blood Vessel Wall

Blood vessels are formed from mesoderm-derived endothelial cells. Arteries, arterioles, and capillaries carry blood from the heart to tissues; venules and veins return blood to the heart. The force exerted by blood on the blood vessel wall is BP and is expressed in mm Hg. Vascular diseases present in various forms, such as bleeding, clotting, stroke, headache, and heart attack. Arteriography was the standard for evaluating arterial disease, but CT angiography and MRI are useful and ever improving. Postoperative concerns include bleeding, clotting, ischemia, stroke, and myocardial infarction.

Antibodies against monocytes and endothelial cells in the sera of patients with atherosclerotic peripheral arterial disease

1988 ◽  
Vol 74 (1-2) ◽  
pp. 99-105 ◽  
Author(s):  
C DANASTASIO ◽  
M IMPALLOMENI ◽  
G MCPHERSON ◽  
W CLEMENTS ◽  
G HOWELLS ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Peripheral Arterial Disease ◽  
Arterial Disease ◽  
Peripheral Arterial
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