AIM: To characterize the human ITB1 gene function as a candidate therapeutic target for cardiovascular disease. We recently identified ITB1, a novel gene that has a role in regulating cell-to-cell communication, promoting endothelial cell sprouting and migration and new blood vessel formation. As chronic inflammation or localized insult to blood vessels are often associated with increased number of inflammatory leukocytes in the adventitia or lesions of blood vessels, in our current research, we are studying the role of ITB1 in endothelial to leukocyte cell communication in normal and disease cardiovascular development. METHODS: To study the role of ITB1 in human cardiovascular disease, live cells from 119 vascular tissue samples were collected from adult patients undergoing venous or arterial surgical procedures. Samples were collected as living cells for tissue culture, gene expression and epigenetic analysis. Samples collected include: 44 venous varices from lower limb, 28 carotid plaque samples from thrombo-endoarterectomy (TEA) procedures, 26 femoral plaques from TEA procedures, 13 abdominal aortic samples from open repair procedures of abdominal aortic aneurysms, 4 femoral superficial veins and 4 surface femoral artery samples from thigh amputations. Peripheral venous blood samples were also collected from both disease patients and healthy patients (control group). RESULTS: Endothelial, macrophage, dendritic, foam cell, lymphocyte and other inflammatory cells were isolated the vascular tissue samples cells by enzymatic and mechanical dissociation followed by fluorescent activated cell sorting (FACS). ITB1 gene expression level was analyzed from both the surgical samples and whole blood from disease patients and controls. Using either transgenically modified cells stably over-expressing ITB1 or cells in which ITB1 expression is down-regulated, we determined that the mechanism by which signaling of endothelial cell to inflammatory cell occurs is by ITB1 regulating vesicle extra cellular trafficking. CONCLUSIONS: Preliminary analysis suggests that ITB1 is a marker for cardiovascular disease. We will investigate whether ITB1 can be used as a candidate marker for early detection of cardiovascular disease. Additionally, as ITB1 may be a target for epigenomic based intervention in disease treatment or management, we are investigating the molecular pathways and targets to identify ITB1 co-interactors.

Characterisation of the human ITB1 gene as a modulator for neo angiogenesis and a candidate therapeutic target for cardiovascular disease / D. Mazzaccaro, L. Muzzarelli, V. Martino, E. Piscitelli, E. Pelucchi, E. Abeni, I. Zucchi, R. Reinbold, G. Nano. ((Intervento presentato al convegno Vascular and Endovascular CONTROVERSIES Update tenutosi a London nel 2018.

Characterisation of the human ITB1 gene as a modulator for neo angiogenesis and a candidate therapeutic target for cardiovascular disease

D. Mazzaccaro
;
L. Muzzarelli;V. Martino;E. Piscitelli;G. Nano
2018-04

Abstract

AIM: To characterize the human ITB1 gene function as a candidate therapeutic target for cardiovascular disease. We recently identified ITB1, a novel gene that has a role in regulating cell-to-cell communication, promoting endothelial cell sprouting and migration and new blood vessel formation. As chronic inflammation or localized insult to blood vessels are often associated with increased number of inflammatory leukocytes in the adventitia or lesions of blood vessels, in our current research, we are studying the role of ITB1 in endothelial to leukocyte cell communication in normal and disease cardiovascular development. METHODS: To study the role of ITB1 in human cardiovascular disease, live cells from 119 vascular tissue samples were collected from adult patients undergoing venous or arterial surgical procedures. Samples were collected as living cells for tissue culture, gene expression and epigenetic analysis. Samples collected include: 44 venous varices from lower limb, 28 carotid plaque samples from thrombo-endoarterectomy (TEA) procedures, 26 femoral plaques from TEA procedures, 13 abdominal aortic samples from open repair procedures of abdominal aortic aneurysms, 4 femoral superficial veins and 4 surface femoral artery samples from thigh amputations. Peripheral venous blood samples were also collected from both disease patients and healthy patients (control group). RESULTS: Endothelial, macrophage, dendritic, foam cell, lymphocyte and other inflammatory cells were isolated the vascular tissue samples cells by enzymatic and mechanical dissociation followed by fluorescent activated cell sorting (FACS). ITB1 gene expression level was analyzed from both the surgical samples and whole blood from disease patients and controls. Using either transgenically modified cells stably over-expressing ITB1 or cells in which ITB1 expression is down-regulated, we determined that the mechanism by which signaling of endothelial cell to inflammatory cell occurs is by ITB1 regulating vesicle extra cellular trafficking. CONCLUSIONS: Preliminary analysis suggests that ITB1 is a marker for cardiovascular disease. We will investigate whether ITB1 can be used as a candidate marker for early detection of cardiovascular disease. Additionally, as ITB1 may be a target for epigenomic based intervention in disease treatment or management, we are investigating the molecular pathways and targets to identify ITB1 co-interactors.
Settore MED/22 - Chirurgia Vascolare
Characterisation of the human ITB1 gene as a modulator for neo angiogenesis and a candidate therapeutic target for cardiovascular disease / D. Mazzaccaro, L. Muzzarelli, V. Martino, E. Piscitelli, E. Pelucchi, E. Abeni, I. Zucchi, R. Reinbold, G. Nano. ((Intervento presentato al convegno Vascular and Endovascular CONTROVERSIES Update tenutosi a London nel 2018.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/587521
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