Cell-based ex vivo delivery of angiogenic growth factors for cardiac repair.
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Biomedical subjects
Publications and source records attributed to Ye Lei.
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Therapeutic angiogenesis improves tissue ischemia by supplementing and supporting the intrinsic process of angiogenesis. Besides direct administration of angiogenic growth factor proteins, injection of naked DNA, non-viral vectors and viral vector constructs carrying angiogenic genes have been used. A novel approach is to achieve therapeutic angiogenesis through cell mediated gene transfer. Genetically modulated cells carrying exogenous genes encoding for angiogenic factors and the cells with inherent ability to secrete angiogenic cytokines, such as bone marrow stem cells, embryonic stem cells and endothelial progenitor cells, have been used to achieve revascularization. This review discusses proof of the concept pre-clinical studies and phase-I/II human trials using VEGF, and cellular angiogenesis at length in the light of the literature and analyzes the problems and considerations of these approaches as a treatment strategy in the clinical perspective for the treatment of ischemic heart disease.
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BACKGROUND: To investigate the dose dependent effect of aprotinin on aggravated pro-inflammatory cytokines in patients with pulmonary hypertension (PH) after cardiopulmonary bypass (CPB). METHODS: Thirty-two patients with pulmonary arterial pressure (PAP) above 60 mmHg were recruited. They were assigned randomly to control (Group A, n = 8), and treated groups (Group B with aprotinin = 0.5 x 10(5) KIU/Kg, and Group C with aprotinin = 1.0 x 10(5) KIU/Kg, n = 12 each group). Blood samples were collected at various intervals of time and analyzed, from "0" hour (before CPB as baseline), at the completion of CPB, 4 hours and 24 hours after CPB, to measure the concentrations of interleukin 1beta (IL-1beta), interleukin-8 (IL-8), interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-alpha). RESULTS: All the biomarkers significantly increased after CPB. There was no significant difference in cytokine levels between Group A and group B after CPB. But IL-1beta, IL-8 and TNF-alpha of Group C were not only significantly lower than Group A (p < 0.05), but also lower than Group B at various time points after CPB (p < 0.05). IL-10 of group C was significantly higher than Group A and Group B after CPB (p < 0.05). CONCLUSIONS: High dose aprotinin can suppress the release of pro-inflammatory cytokines IL-1beta, IL-8 and TNF-alpha, and enhance the release of IL-10 in patients with PH after CPB. For patients having PH, there exists a simple and potential way to reduce the inflammatory response by applying high dose aprotinin.
OBJECTIVE: Pulmonary arterial hypertension [PAH] and cardiopulmonary bypass [CPB] induce systemic inflammatory cytokines that are critical factors related to postoperative mortality of open heart surgery. We studied the expression of proinflammatory cytokines and cyclic guanosine monophosphate [cGMP] in patients suffering from PAH after CPB. METHODS: Seventy-six patients who underwent valve replacement surgery were recruited and divided into two groups according to their pulmonary arterial pressure [< 50 mmHg for Group A and > or = 50 mmHg for Group B]. Blood samples were taken to measure the concentrations of interleukin-1 beta [IL-1 beta], tumour necrosis factor alpha [TNF-alpha], interleukin-10 [IL-10] and cGMP. RESULTS: IL-1 beta and TNF-alpha were significantly higher in Group B [28.6 +/- 9.1 mmHg] than in Group A [65.8 +/- 10.2 mmHg] at baseline. After CPB, IL-1 beta of both groups rose significantly, while only TNF-alpha of Group B rose significantly higher. There were significant differences between the two groups after CPB. IL-10 and cGMP in Group B were lower than in Group A at baseline. They all decreased significantly after CPB. Significant differences were seen between the groups after CPB. CONCLUSION: Patients suffering from PAH had different levels of proinflammatory and anti-inflammatory cytokines compared to normal patients. PAH aggravates the production of IL-1 beta and TNF-alpha, while it decreases the production of IL-10 and cGMP after CPB.