scholarly journals PC230. Microbial Colonization Restores Neointimal Hyperplasia Development After Arterial Injury in Germ-Free Mice

2019 ◽  
Vol 69 (6) ◽  
pp. e267-e268
Author(s):  
Edmund B. Chen ◽  
Katherine Shapiro ◽  
Thomas Kuntz ◽  
Betty Theriault ◽  
Michael Nooromid ◽  
...  
Keyword(s):  
Neointimal Hyperplasia ◽  
Arterial Injury ◽  
Microbial Colonization ◽  
Germ Free

scholarly journals Microbial Colonization of Germ‐Free Mice Restores Neointimal Hyperplasia Development After Arterial Injury

2020 ◽  
Vol 9 (5) ◽  
Author(s):  
Edmund B. Chen ◽  
Katherine E. Shapiro ◽  
Kelly Wun ◽  
Thomas Kuntz ◽  
Betty R. Theriault ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Neointimal Hyperplasia ◽  
Arterial Injury ◽  
Microbial Colonization ◽  
Causative Role ◽  
Fecal Transplantation ◽  
Germ Free ◽  
Comparison Groups ◽  
Arterial Restenosis

Background The potential role of the gut microbiome in cardiovascular diseases is increasingly evident. Arterial restenosis attributable to neointimal hyperplasia after cardiovascular procedures such as balloon angioplasty, stenting, and bypass surgery is a common cause of treatment failure, yet whether gut microbiota participate in the development of neointimal hyperplasia remains largely unknown. Methods and Results We performed fecal microbial transplantation from conventionally raised male C57BL/6 mice to age‐, sex‐, and strain‐matched germ‐free mice. Five weeks after inoculation, all mice underwent unilateral carotid ligation. Neointimal hyperplasia development was quantified after 4 weeks. Conventionally raised and germ‐free cohorts served as comparison groups. Conclusions Germ‐free mice have significantly attenuated neointimal hyperplasia development compared with conventionally raised mice. The arterial remodeling response is restored by fecal transplantation. Our results describe a causative role of gut microbiota in contributing to the pathogenesis of neointimal hyperplasia.

scholarly journals Su1093 – Fecal Transplantation Restores Neointimal Hyperplasia Development After Arterial Injury in Germ-Free Mice

2019 ◽  
Vol 156 (6) ◽  
pp. S-1438
Author(s):  
Edmund Chen ◽  
Katherine E. Shapiro ◽  
Betty Theriault ◽  
Michael Nooromid ◽  
Kelly Wun ◽  
...  
Keyword(s):  
Neointimal Hyperplasia ◽  
Arterial Injury ◽  
Fecal Transplantation ◽  
Germ Free

Inhibition of Leucocyte and Platelet Adhesion Reduces Neointimal Hyperplasia after Arterial Injury

1997 ◽  
Vol 77 (04) ◽  
pp. 783-788 ◽  
Author(s):  
Paolo Golino ◽  
Giuseppe Ambrosio ◽  
Massimo Ragni ◽  
Plinio Cirillo ◽  
Nicolino Esposito ◽  
...  
Keyword(s):  
Coronary Angioplasty ◽  
Neointimal Hyperplasia ◽  
Rabbit Model ◽  
Arterial Injury ◽  
Platelet Glycoprotein ◽  
Beneficial Effects ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Factor Interaction ◽  
Adhesion Complex

SummaryRestenosis following coronary angioplasty is thought to result from migration and proliferation of medial smooth muscle cells. However, the factors that initiate this proliferation are still unknown. In a rabbit model of carotid artery injury, we tested the hypothesis that activated platelets and leucocytes might contribute to the development of neointimal hyperplasia. Following arterial injury, rabbits received either no treatment, R15.7, a monoclonal antibody against the leucocyte CD ll/CD 18 adhesion complex, aurintricarboxylic acid (ATA), a sub stance that inhibits platelet glycoprotein Ib-von Willebrand factor interaction, or the combination of R15.7 and ATA. After 21 days, the extent of neointimal hyperplasia was evaluated by planimetry on histological arterial sections. The area of neointima averaged 0.51 ±0.07 mm2 in control animals and it was significantly reduced by administrationof either R15.7 or ATA alone to 0.12 ± 0.05 and 0.20 ±0.01 mm2, respectively (p <0.05 vs controls for both groups). The animals that received the combination of R15.7 and ATA showed a further reduction in neointimal hyperplasia, as compared to animals that received ATA alone (p <0.05 vs ATA alone). These data indicate that platelets and leucocytes play animportant role in the pathophysi ology of neointimal hyperplasia in this experimental model. Interven tions that reduce platelet and leucocyte adhesion to vessel wall might have beneficial effects in reducing restenosis following coronary angioplasty.

Abstract 15691: The Novel High Mobility Group Protein Hmgxb4 Promotes Neointimal Formation in Response to Arterial Injury

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
xiangqin he ◽  
Kunzhe Dong ◽  
Jian Shen ◽  
Islam Osman ◽  
Guoqing Hu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Neointimal Hyperplasia ◽  
Critical Role ◽  
High Mobility ◽  
Arterial Injury ◽  
The Novel ◽  
Neointimal Formation ◽  
Vsmc Proliferation ◽  
And Migration

Introduction: Restenosis after percutaneous intervention is predominantly attributed to proliferation and migration of vascular smooth muscle cells (VSMCs). However, the key regulators responsible for VSMC proliferation and migration remain to be identified. Hypothesis: We previously reported that the novel high mobility group (HMG) nuclear protein HMGXB4 (HMG-Box containing 4) plays a critical role in the de-differentiation of vascular smooth muscle cells in vitro and in acute inflammatory response to septic shock. We hypothesize that HMGXB4 is critical for neointimal hyperplasia in response to inflammatory stimuli. Methods and Results: We found that the expression of HMGXB4 is dramatically induced in ligation or wire injury-induced neointimal hyperplasia and correlated with the activation of inflammatory signaling in mice. Using an inducible smooth muscle-specific Hmgxb4 KO (knockout) mice model, we found specific KO of Hmgxb4 in VSMCs ameliorates ligation- or wire- injury induced neointimal formation. Among an array of growth factors and inflammation cytokines, we found that TNFα and INFγ effectively induces the expression of HMGXB4 in VSMCs and correlates with the VSMC proliferation in vitro. Furthermore, we found deletion of HMGXB4 attenuates while over-expression of HMGXB4 promotes inflammation cytokines-induced VSMC proliferation in vitro. These results suggest injury-induced inflammatory signal triggers HMGXB4 induction, which, in turn, promotes the VSMC proliferation and neointimal formation. Conclusions: Our study not only demonstrates a critical role of HMGXB4 in promoting neointimal hyperplasia in response the arterial injury, but also suggests HMGXB4 is a potential novel target for the management of restenosis in human.

scholarly journals Oxidized LDL receptor LOX-1 is involved in neointimal hyperplasia after balloon arterial injury in a rat model

2006 ◽  
Vol 69 (1) ◽  
pp. 263-271 ◽  
Author(s):  
J HINAGATA ◽  
M KAKUTANI ◽  
T FUJII ◽  
T NARUKO ◽  
N INOUE ◽  
...  
Keyword(s):  
Rat Model ◽  
Oxidized Ldl ◽  
Neointimal Hyperplasia ◽  
Ldl Receptor ◽  
Arterial Injury

scholarly journals Insulin enhances the effect of nitric oxide at inhibiting neointimal hyperplasia in a rat model of type 1 diabetes

2010 ◽  
Vol 299 (3) ◽  
pp. H772-H779 ◽  
Author(s):  
Vinit N. Varu ◽  
Sadie S. Ahanchi ◽  
Melissa E. Hogg ◽  
Hussein A. Bhikhapurwala ◽  
Amy Chen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Type 1 Diabetes ◽  
Neointimal Hyperplasia ◽  
Arterial Injury ◽  
Diabetic Rats ◽  
Insulin Administration ◽  
No Donor ◽  
Normal Glucose ◽  
High Insulin

Diabetes confers greater restenosis from neointimal hyperplasia following vascular interventions. While localized administration of nitric oxide (NO) is known to inhibit neointimal hyperplasia, the effect of NO in type 1 diabetes is unknown. Thus the aim of this study was to determine the efficacy of NO following arterial injury, with and without exogenous insulin administration. Vascular smooth muscle cells (VSMC) from lean Zucker (LZ) rats were exposed to the NO donor, DETA/NO, following treatment with different glucose and/or insulin concentrations. DETA/NO inhibited VSMC proliferation in a concentration-dependent manner to a greater extent in VSMC exposed to normal-glucose vs. high-glucose environments, and even more effectively in normal-glucose/high-insulin and high-glucose/high-insulin environments. G0/G1 cell cycle arrest and cell death were not responsible for the enhanced efficacy of NO in these environments. Next, type 1 diabetes was induced in LZ rats with streptozotocin. The rat carotid artery injury model was performed. Type 1 diabetic rats experienced no significant reduction in neointimal hyperplasia following arterial injury and treatment with the NO donor PROLI/NO. However, daily administration of insulin to type 1 diabetic rats restored the efficacy of NO at inhibiting neointimal hyperplasia (60% reduction, P < 0.05). In conclusion, these data demonstrate that NO is ineffective at inhibiting neointimal hyperplasia in an uncontrolled rat model of type 1 diabetes; however, insulin administration restores the efficacy of NO at inhibiting neointimal hyperplasia. Thus insulin may play a role in regulating the downstream beneficial effects of NO in the vasculature.

scholarly journals Crucial Role of the CCL2/CCR2 Axis in Neointimal Hyperplasia After Arterial Injury in Hyperlipidemic Mice Involves Early Monocyte Recruitment and CCL2 Presentation on Platelets

2004 ◽  
Vol 95 (11) ◽  
pp. 1125-1133 ◽  
Author(s):  
Andreas Schober ◽  
Alma Zernecke ◽  
Elisa A. Liehn ◽  
Philipp von Hundelshausen ◽  
Sandra Knarren ◽  
...  
Keyword(s):  
Crucial Role ◽  
Neointimal Hyperplasia ◽  
Arterial Injury ◽  
Monocyte Recruitment

scholarly journals Microbial Colonization in Adulthood Shapes the Intestinal Macrophage Compartment

2019 ◽  
Vol 13 (9) ◽  
pp. 1173-1185 ◽  
Author(s):  
Franziska Schmidt ◽  
Katja Dahlke ◽  
Arvind Batra ◽  
Jacqueline Keye ◽  
Hao Wu ◽  
...  
Keyword(s):  
Intestinal Wall ◽  
Functional Restoration ◽  
Microbial Colonization ◽  
Germ Free ◽  
Adult Mice ◽  
Immune Mediated ◽  
Complete Restoration ◽  
Specific Pathogen ◽  
Intestinal Macrophage ◽  
The Impact

Abstract Background and Aims Contact with distinct microbiota early in life has been shown to educate the mucosal immune system, hence providing protection against immune-mediated diseases. However, the impact of early versus late colonization with regard to the development of the intestinal macrophage compartment has not been studied so far. Methods Germ-free mice were colonized with specific-pathogen-free [SPF] microbiota at the age of 5 weeks. The ileal and colonic macrophage compartment were analysed by immunohistochemistry, flow cytometry, and RNA sequencing 1 and 5 weeks after colonization and in age-matched SPF mice, which had had contact with microbiota since birth. To evaluate the functional differences, dextran sulfate sodium [DSS]-induced colitis was induced, and barrier function analyses were undertaken. Results Germ-free mice were characterized by an atrophied intestinal wall and a profoundly reduced number of ileal macrophages. Strikingly, morphological restoration of the intestine occurred within the first week after colonization. In contrast, ileal macrophages required 5 weeks for complete restoration, whereas colonic macrophages were numerically unaffected. However, following DSS exposure, the presence of microbiota was a prerequisite for colonic macrophage infiltration. One week after colonization, mild colonic inflammation was observed, paralleled by a reduced inflammatory response after DSS treatment, in comparison with SPF mice. This attenuated inflammation was paralleled by a lack of TNFα production of LPS-stimulated colonic macrophages from SPF and colonized mice, suggesting desensitization of colonized mice by the colonization itself. Conclusions This study provides the first data indicating that after colonization of adult mice, the numeric, phenotypic, and functional restoration of the macrophage compartment requires the presence of intestinal microbiota and is time dependent.

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