Adenovirus-Mediated Human Tissue Kallikrein Gene Delivery Inhibits Neointima Formation Induced by Interruption of Blood Flow in Mice

Emanueli, Costanza; Salis, Maria Bonaria; Chao, Julie; Chao, Lee; Agata, Jun; Lin, King‐Fu; Munaò, Antonella; Straino, Stefania; Minasi, Alessandra; Capogrossi, Maurizio C.; Madeddu, Paolo

doi:10.1161/01.atv.20.6.1459

Cited by 28 publications

(16 citation statements)

References 44 publications

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“…Furthermore, a low-dose combination of an ACE inhibitor and the diuretic indapamide induces neovascularization in ischemic rat hindlimbs (122). Gene transfer of tissue kallikrein increased urinary kinins, cGMP, and cAMP and had a protective effect on neointima formation (40). This protective effect was not seen when gene transfer was performed in the BKB2R Ϫ/Ϫ mouse (40).…”

Section: The Interaction Of the Plasma Kks And Ras In Angiogenesismentioning

confidence: 99%

The kallikrein-kinin and the renin-angiotensin systems have a multilayered interaction

Schmaier

2003

American Journal of Physiology-Regulatory, Integrative and Comp

150

127

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Understanding the physiological role of the plasma kallikrein-kinin system (KKS) has been hampered by not knowing how the proteins of this proteolytic system, when assembled in the intravascular compartment, become activated under physiological conditions. Recent studies indicate that the enzyme prolylcarboxypeptidase, an ANG II inactivating enzyme, is a prekallikrein activator. The ability of prolylcarboxypeptidase to act in the KKS and the renin-angiotensin system (RAS) indicates a novel interaction between these two systems. This interaction, along with the roles of angiotensin converting enzyme, cross talk between bradykinin and angiotensin-(1-7) action, and the opposite effects of activation of the ANG II receptors 1 and 2 support a hypothesis that the plasma KKS counterbalances the RAS. This review examines the interaction and cross talk between these two protein systems. This analysis suggests that there is a multilayered interaction between these two systems that are important for a wide array of physiological functions.

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Section: The Interaction Of the Plasma Kks And Ras In Angiogenesismentioning

confidence: 99%

The kallikrein-kinin and the renin-angiotensin systems have a multilayered interaction

Schmaier

2003

American Journal of Physiology-Regulatory, Integrative and Comp

150

127

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“…The response to carotid artery ligation has been shown to be mediated by factors affecting inflammation, 14 vascular tone, 16,68,69 plasma proteins, 1,11,12,70 cytoskeletal components, 50 and hormones/ growth factors. 71,72 After ligation, OPN-null mice demonstrated greater initial constrictive remodeling and less neointima formation compared with wild type.…”

Section: Myers Et Al Arterial Physiology In Opn-null Micementioning

confidence: 99%

Alterations of Arterial Physiology in Osteopontin-Null Mice

Myers

Harmon

Lindner

et al. 2003

ATVB

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Objective-In this study, we characterized the effects of an osteopontin (OPN)-null mutation in normal arterial function and remodeling in a murine model. Methods and Results-OPN-null mutant mice were compared with wild-type mice before and after carotid artery ligation.Before ligation, OPN-null mice had increased heart rate, lower blood pressure, and increased circulating lymphocytes compared with wild-type mice. OPN-null vessels also demonstrated greater compliance accompanied by a loosely organized collagen network. After carotid artery ligation, significant differences were also found in the remodeling response of OPN-null animals. 16,17 and shear stress. 9,18,19 We previously found that inhibiting osteopontin (OPN) function after endothelial denudation led to a significant decrease in the extent of neointimal formation in rats. 20 In this study, the arterial effects resulting from the removal of OPN (product of the spp1 gene) were examined.OPN is a secreted integrin-binding protein that is present in small amounts in uninjured arteries 21 but is abundantly expressed by smooth muscle cells, endothelial cells, 21,22 and activated inflammatory cells [23][24][25] in injured arteries. Abundant OPN expression has also been observed in human atherosclerotic lesions 26 and thoracic aneurysms. 27 The functional significance of this increased vascular expression was suggested by work demonstrating OPN activity as a chemoattractant/adhesive substrate for endothelial cells 28 and vascular smooth muscle cells, 29 an inhibitor of vascular smooth muscle calcification, 30,31 and a chemoattractant/activator of inflammatory cells. 32,33 In vivo studies confirmed these important functions of OPN during tissue remodeling and repair. Chiba et al 34 observed that hematopoietic cell overexpression of OPN resulted in increased atherosclerotic lesion formation. In OPN-null mice, recent data have indicated that the nonredundant functions of OPN in vivo involve widespread participation in tissue remodeling, inflammation, 24,32 tumor progression, 35 and angiogenesis. 36 Defective tissue remodeling on an OPN-null background has been observed in tissues including the myocardium, 37 bone, 36,38 -40 skin, 41 kidney, 42-44 lymph nodes, 45 joints, 46 and malignant tissues. 35 Two phenotypes that characterize many of these studies are a change in the immune response and altered matrix remodeling. Therefore, the widespread participation of OPN in tissue remodeling is likely due to its unique functions in basic repair processes. In addition, the role of OPN as a physiological inhibitor of vascular calcification was demonstrated in studies showing that spontaneous vascular calcification in the matrix of Gla protein-null mice was significantly increased on an OPN-null background. 47 Recently, constitutive overexpression of OPN in mice was observed to result in increased neointima formation after cuffing of the femoral artery. 48 Interestingly, this overexpression of OPN in uninjured mice did not result in accumulation of leukocytes in the vessel...

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“…Of the 35 angiogenesis trials either ongoing or completed (as registered on the NIH website), 22 utilize VEGF as either plasmid DNA or in an adenoviral vector. A number of other genes have been studied in vitro and in animal models with varying success including FGF, 127,138 angiopoietin-1, 139 hepatocyte growth factor, 140−143 eNOS, 144 hypoxia induced factor-1,α 145,146 tissue kallikrein, 147,148 Del-1, 149 and thrombopoietin. 150 VEGF, also known as vascular permeability factor and vasculotropin, is a glycoprotein that exists in six different sizes including 121,138,145,165,189, and 206 amino acids.…”

Section: Candidate Genesmentioning

confidence: 99%

The Emerging Role of Gene Therapy in the Treatment of Cardiovascular Diseases

Barbato

Kibbe

Tzeng

2003

Critical Reviews in Clinical Laboratory Sciences

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Cardiovascular disease is the number one source of morbidity and mortality in the United States. Therapies directed at a variety of cardiovascular diseases have blossomed over the last several decades. The advent of gene therapy, first as an intriguing tool, and subsequently with the early successes of gene trials involving the treatment of SCID, led to the development of gene therapy as a potentially exciting and viable therapy in cardiovascular diseases. A variety of novel vector technologies and delivery systems have been developed to more efficiently deliver the gene product to the desired organ or tissue bed. Early clinical trials focused on stimulating angiogenesis. Subsequently, a number of other aspects of cardiovascular disease have been identified as potential targets for gene therapy, including the prevention of restenosis, the prevention and treatment of thrombosis, and the prevention of transplant vasculopathy. With over forty clinical human trials either completed or currently enrolling, cardiovascular gene therapy has proven to be safe and initial results suggest its efficacy.

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Adenovirus-Mediated Human Tissue Kallikrein Gene Delivery Inhibits Neointima Formation Induced by Interruption of Blood Flow in Mice

Cited by 28 publications

References 44 publications

The kallikrein-kinin and the renin-angiotensin systems have a multilayered interaction

The kallikrein-kinin and the renin-angiotensin systems have a multilayered interaction

Alterations of Arterial Physiology in Osteopontin-Null Mice

The Emerging Role of Gene Therapy in the Treatment of Cardiovascular Diseases

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