Endothelial Cells Overexpressing Interleukin-8 Receptors Reduce Inflammatory and Neointimal Responses to Arterial Injury

Xing, Dong; Liu, Mingchun; Gong, Kaizheng; Yang, Zhonghai; Yu, Hao; Hage, Fadi G.; Oparil, Suzanne; Chen, Yiu-Fai

doi:10.1161/circulationaha.111.078436

Cited by 30 publications

(72 citation statements)

References 35 publications

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“…To perform the femoral vein catheterization, rats were anesthetized with ketamine (80 mg/kg ip) and xylazine (15 mg/kg ip), and the right femoral vein was isolated. A PE catheter (PE-10 fused with PE-50) was implanted into right femoral vein for transfusion of ECs (23,35). During the surgery, respiratory rate were monitored continuously and toe pinch reflex was tested every 3 to 5 min to verify the depth of anesthesia.…”

Section: Animals and Proceduresmentioning

confidence: 99%

“…Results are means Ϯ SE; (n) ϭ number of rats. with a GFP gene were prepared as described previously (35). Transduced ECs or vehicle were transfused through the femoral venous catheter that had been implanted one day before the LAD coronary artery ligation surgery.…”

Section: Animals and Proceduresmentioning

confidence: 99%

“…Rat aortic ECs (purchased from VEC Technologies, Cat No. RAEC/T-75) that overexpress IL8RA-GFP, IL8RB-GFP, or Null-GFP (empty adenoviral vector control) were generated using adenoviral vectors that contain human IL8RA and/or IL8RB cDNAs and the GFP gene using the AdEasy Adenoviral Vector System (Stratagene) as reported previously (35).…”

Section: Animals and Proceduresmentioning

confidence: 99%

“…We have demonstrated that acute intravenous transfusion of ECs equipped with the neutrophil IL-8 receptors results in targeting and adherence of the transformed ECs to injured carotid arteries, decreasing infiltration of activated neutrophils, inhibiting pro-inflammatory responses, and reducing neointima formation (adverse remodeling) (35).…”

mentioning

confidence: 99%

“…We have recently developed an innovative strategy to overcome the hurdles of cell-based therapy by intravenously transfusing endothelial cells (ECs) overexpressing IL8RA and IL8RB into rats with balloon injury of the carotid artery (35). We have demonstrated that acute intravenous transfusion of ECs equipped with the neutrophil IL-8 receptors results in targeting and adherence of the transformed ECs to injured carotid arteries, decreasing infiltration of activated neutrophils, inhibiting pro-inflammatory responses, and reducing neointima formation (adverse remodeling) (35).…”

mentioning

confidence: 99%

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Endothelial cells overexpressing IL-8 receptor reduce cardiac remodeling and dysfunction following myocardial infarction

Zhao

Zhang

Xing

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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The endothelium is a dynamic component of the cardiovascular system that plays an important role in health and disease. This study tested the hypothesis that targeted delivery of endothelial cells (ECs) overexpressing neutrophil membrane IL-8 receptors IL8RA and IL8RB reduces acute myocardial infarction (MI)-induced left ventricular (LV) remodeling and dysfunction and increases neovascularization in the area at risk surrounding the infarcted tissue. MI was created by ligating the left anterior descending coronary artery in 12-wk-old male Sprague-Dawley rats. Four groups of rats were studied: group 1: sham-operated rats without MI or EC transfusion; group 2: MI rats with intravenous vehicle; group 3: MI rats with transfused ECs transduced with empty adenoviral vector (Null-EC); and group 4: MI rats with transfused ECs overexpressing IL8RA/RB (1.5 ϫ 10 6 cells post-MI). Two weeks after MI, LV function was assessed by echocardiography; infarct size was assessed by triphenyltetrazolium chloride (live tissue) and picrosirus red (collagen) staining, and capillary density and neutrophil infiltration in the area at risk were measured by CD31 and MPO immunohistochemical staining, respectively. When compared with the MI ϩ vehicle and MI-Null-EC groups, transfusion of IL8RA/RB-ECs decreased neutrophil infiltration and pro-inflammatory cytokine expression and increased capillary density in the area at risk, decreased infarct size, and reduced MI-induced LV dysfunction. These findings provide proof of principle that targeted delivery of ECs is effective in repairing injured cardiac tissue. Targeted delivery of ECs to infarcted hearts provides a potential novel strategy for the treatment of acute MI in humans. myocardial infarction; cell therapy; endothelial cells; interleukin-8 receptors; neovascularization CELL-BASED THERAPIES FOR CARDIOVASCULAR diseases have proliferated over the past decade, but with limited success (13, 30). Cell-based therapies have been shown to alleviate left ventricular (LV) remodeling and dysfunction after acute myocardial infarction (MI) in animal models and in humans (1,2,4,5,15,16,19,20,22,26,31,32). Intracoronary administration of stem cells (e.g., bone marrow-derived cells or circulating cardiac progenitor cells) can be effective in regenerating cardiac tissue and ameliorating LV remodeling and dysfunction in rodent models of acute MI, both in the setting of permanent coronary occlusion and as a result of transient occlusion followed by reperfusion (15,16,26,31,32). An important limitation of this approach is that because these cells lack a selective homing device targeting ischemic/infarcted tissues, they must be injected directly into the affected myocardium or infused into the aortic root, procedures that are invasive, costly, and difficult to adapt for widespread clinical use. Other major hurdles for successful cell therapies include 1) cell type selection (e.g., progenitor vs. differentiated), 2) cell delivery mode (e.g., peripheral vs. directly into tissue), 3) timing of cell delivery (e....

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Section: Animals and Proceduresmentioning

confidence: 99%

Section: Animals and Proceduresmentioning

confidence: 99%

Section: Animals and Proceduresmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Endothelial cells overexpressing IL-8 receptor reduce cardiac remodeling and dysfunction following myocardial infarction

Zhao

Zhang

Xing

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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Induced Pluripotent Stem Cell-Derived Endothelial Cells Overexpressing Interleukin-8 Receptors A/B and/or C-C Chemokine Receptors 2/5 Inhibit Vascular Injury Response

Giordano

Zhao

Chen

et al. 2017

Stem Cells Translational Medicine

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Recruitment of neutrophils and monocytes/macrophages to the site of vascular injury is mediated by binding of chemoattractants to interleukin (IL) 8 receptors RA and RB (IL8RA/B) C‐C chemokine receptors (CCR) 2 and 5 expressed on neutrophil and monocyte/macrophage membranes. Endothelial cells (ECs) derived from rat‐induced pluripotent stem cells (RiPS) were transduced with adenovirus containing cDNA of IL8RA/B and/or CCR2/5. We hypothesized that RiPS‐ECs overexpressing IL8RA/B (RiPS‐IL8RA/B‐ECs), CCR2/5 (RiPS‐CCR2/5‐ECs), or both receptors (RiPS‐IL8RA/B+CCR2/5‐ECs) will inhibit inflammatory responses and neointima formation in balloon‐injured rat carotid artery. Twelve‐week‐old male Sprague‐Dawley rats underwent balloon injury of the right carotid artery and intravenous infusion of (a) saline vehicle, (b) control RiPS‐Null‐ECs (ECs transduced with empty virus), (c) RiPS‐IL8RA/B‐ECs, (d) RiPS‐CCR2/5‐ECs, or (e) RiPS‐IL8RA/B+CCR2/5‐ECs. Inflammatory mediator expression and leukocyte infiltration were measured in injured and uninjured arteries at 24 hours postinjury by enzyme‐linked immunosorbent assay (ELISA) and immunohistochemistry, respectively. Neointima formation was assessed at 14 days postinjury. RiPS‐ECs expressing the IL8RA/B or CCR2/5 homing device targeted the injured arteries and decreased injury‐induced inflammatory cytokine expression, neutrophil/macrophage infiltration, and neointima formation. Transfused RiPS‐ECs overexpressing IL8RA/B and/or CCR2/5 prevented inflammatory responses and neointima formation after vascular injury. Targeted delivery of iPS‐ECs with a homing device to inflammatory mediators in injured arteries provides a novel strategy for the treatment of cardiovascular diseases. Stem Cells Translational Medicine 2017;6:1168–1177

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Pulmonary Hypertension in Patients Without Pulmonary Arterial Hypertension

Huston

Hatton

Ryan

2016

Pulmonary Hypertension

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Endothelial Cells Overexpressing Interleukin-8 Receptors Reduce Inflammatory and Neointimal Responses to Arterial Injury

Cited by 30 publications

References 35 publications

Endothelial cells overexpressing IL-8 receptor reduce cardiac remodeling and dysfunction following myocardial infarction

Endothelial cells overexpressing IL-8 receptor reduce cardiac remodeling and dysfunction following myocardial infarction

Induced Pluripotent Stem Cell-Derived Endothelial Cells Overexpressing Interleukin-8 Receptors A/B and/or C-C Chemokine Receptors 2/5 Inhibit Vascular Injury Response

Pulmonary Hypertension in Patients Without Pulmonary Arterial Hypertension

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