Abstract:
:First-generation, E1-deleted adenoviral vectors (E1-AV) can transduce the vascular endothelium with high efficiency, but their use is limited by the resulting acute endothelial injury and the long-term development of intimal hyperplasia. To reduce the impact of viral proteins on the gene-modified cells, a second-generation adenoviral vector with an additional pair of deletions in the E4 region was developed. To determine whether this E1/E4-AV vector would be useful for vascular gene transfer, we directly compared the efficiency of gene transfer to uninjured rabbit carotid arteries using either an E1/E4-AV or an E1-AV vector encoding beta-galactosidase. Both vectors efficiently transduced vascular endothelium; however, the E1/E4-AV vector gene-modified vessels showed higher beta-galactosidase expression 10 days after gene transfer. Importantly, the E1/E4-AV vector produced substantially less endothelial cell activation, less inflammation, and reduced neointimal hyperplasia compared with the E1-AV vector-treated vessels. The E1-AV vector-transduced vessels also demonstrated significantly impaired endothelium-dependent relaxation whereas the E1/E4-AV vector did not impact vasomotor function, even at doses of virus in 5-fold excess of the amount required for >90% transduction of the endothelium. We conclude that the E1/E4-AV vector is superior to the E1-AV vector for vascular gene therapy because of the prolonged transgene expression, reduced vascular inflammation, reduced intimal hyperplasia, and maintenance of normal vasomotor function.
journal_name
Circ Resjournal_title
Circulation researchauthors
Qian HS,Channon K,Neplioueva V,Wang Q,Finer M,Tsui L,George SE,McArthur Jdoi
10.1161/hh0901.090926subject
Has Abstractpub_date
2001-05-11 00:00:00pages
911-7issue
9eissn
0009-7330issn
1524-4571journal_volume
88pub_type
杂志文章abstract::Phospholamban is a key regulatory protein that defines diastolic function. Proinflammatory cytokines interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) can depress contractility and intracellular Ca2+ currents and transients. An alteration in phospholamban expression is a possible pathway by wh...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.81.4.493
更新日期:1997-10-01 00:00:00
abstract::The role of the central nervous system in the mechanism(s) involved in acute carotid baroreflex resetting was studied in six conscious, chronically instrumented, aortic-denervated dogs. Dogs were prepared for reversible vascular isolation of the carotid sinuses. Acute baroreflex resetting was induced by holding the le...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.65.1.63
更新日期:1989-07-01 00:00:00
abstract:RATIONALE:Obesity leads to increased ischemic heart disease (IHD) risk, but the risk is thought to be mediated through intermediate variables and may not be caused by increased weight per se. OBJECTIVE:To test the hypothesis that the increased IHD risk because of obesity is mediated through lipoproteins, blood pressur...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.304846
更新日期:2015-02-13 00:00:00
abstract::To test the hypothesis that early interventional treatment with insulin-like growth factor-1 (IGF-1) alleviates subsequent development of dilated cardiomyopathy, cardiac-specific IGF-1 expression was introduced by selective cross-breeding into a transgenic mouse model of heart failure that displays phenotypic characte...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000013780.77774.75
更新日期:2002-04-05 00:00:00
abstract::Patients with peripheral artery disease (PAD) are at heightened risk of both systemic cardiovascular adverse events, as well as limb-related morbidity. The optimal management of patients with PAD requires a comprehensive treatment strategy incorporating both lifestyle changes, including smoking cessation and exercise,...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.114.303505
更新日期:2015-04-24 00:00:00
abstract:RATIONALE:Lymphatic vasculature plays important roles in tissue fluid homeostasis maintenance and in the pathology of human diseases. Yet, the molecular mechanisms that control lymphatic vessel maturation remain largely unknown. OBJECTIVE:We analyzed the gene expression profiles of ex vivo isolated lymphatic endotheli...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.112.269399
更新日期:2012-08-03 00:00:00
abstract:RATIONALE:Activation of Nox1 initiates redox-dependent signaling events crucial in the pathogenesis of vascular disease. Selective targeting of Nox1 is an attractive potential therapy, but requires a better understanding of the molecular modifications controlling its activation. OBJECTIVE:To determine whether posttran...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.115.304267
更新日期:2014-11-07 00:00:00
abstract::Pulsatile pulmonary hemodynamics were analyzed in a chronic awake canine high flow model. Standard mean flow and pulsatile flow hemodynamics were measured and alterations in the proximal pulmonary vascular physical properties were quantified by the characteristic impedance (Zo). Pulmonary vascular resistance (PVR), wh...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.45.2.267
更新日期:1979-08-01 00:00:00
abstract::Isolated adult rat hearts perfused in an isovolumic mode were used to study the effects of sodium-potassium pump inhibition and sodium-calcium exchange alterations on the tissue content of adenosine triphosphate, phosphocreatine, inorganic phosphate, and intracellular pH, all measured by phosphorus-31 nuclear magnetic...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.58.4.539
更新日期:1986-04-01 00:00:00
abstract::Two gap junction proteins, connexin43 (Cx43) and connexin45 (Cx45), are coexpressed in many cardiac and other cells. Homomeric channels formed by these proteins differ in unitary conductance, permeability, and regulation. We sought to determine the ability of Cx43 and Cx45 to oligomerize with each other to form hetero...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000019580.64013.31
更新日期:2002-05-31 00:00:00
abstract::The contractile response of the aged adult heart to beta-adrenergic stimulation is known to be reduced compared with the young adult heart. Since endogenous adenosine exerts an antiadrenergic action in the heart, this study was undertaken to determine if the basal endogenous level of myocardial adenosine increases wit...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.66.5.1381
更新日期:1990-05-01 00:00:00
abstract::Chronic inflammation in white adipose tissue (WAT) is positively associated with obesity, insulin resistance (IR) and the development of type 2 diabetes. The proinflammatory cytokine MIF (macrophage migration inhibitory factor) is an essential, upstream component of the inflammatory cascade. This study examines whethe...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.199166
更新日期:2009-07-02 00:00:00
abstract::Studies were carried out to determine the contribution of cardiopulmonary receptors to the renal responses to head-out water immersion in the nonhuman primate. Immersion to the suprasternal notch was associated with significant increases in central venous pressure, urine flow, and sodium excretion. The increased sodiu...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.42.2.263
更新日期:1978-02-01 00:00:00
abstract::In clinical trials, aldosterone antagonists decrease cardiovascular mortality and ischemia by unknown mechanisms. The steroid hormone aldosterone acts by binding to the mineralocorticoid receptor (MR), a ligand-activated transcription factor. In humans, aldosterone causes MR-dependent endothelial cell (EC) dysfunction...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.108.174235
更新日期:2008-06-06 00:00:00
abstract:RATIONALE:Accurate knowledge of the cellular composition of the heart is essential to fully understand the changes that occur during pathogenesis and to devise strategies for tissue engineering and regeneration. OBJECTIVE:To examine the relative frequency of cardiac endothelial cells, hematopoietic-derived cells, and ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.115.307778
更新日期:2016-02-05 00:00:00
abstract::Peripheral blood (PB)-derived CD14+ monocytes were shown to transdifferentiate into endothelial cell (EC) lineage cells and contribute to neovascularization. We investigated whether bone marrow (BM)- or PB-derived CD34-/CD14+ cells are involved in reendothelialization after carotid balloon injury. Although neither hem...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000099245.08637.CE
更新日期:2003-11-14 00:00:00
abstract::Mitochondrial quality is a crucial determinant of cell viability, and mitochondrial autophagy plays a central role in this control mechanism. Based on studies in yeast, numerous investigations of this process have been conducted, and the framework of mammalian mitochondrial autophagy is progressively appearing. Howeve...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.116.303790
更新日期:2015-04-10 00:00:00
abstract::The changes in renal function produced by endogenous synthesis of prostaglandins by the kidney were evaluated by infusing sodium arachidonate, the prescursor of the prostaglandins, into one renal artery of the dog. These changes were compared with those produced by similar infusions on performed prostaglandin (PG) E2 ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.36.1.197
更新日期:1975-01-01 00:00:00
abstract:RATIONALE:Previous studies on the relationship between diabetes and arterial stiffness were mostly cross-sectional. A few longitudinal studies focused on one single direction. Whether the association between arterial stiffness and diabetes is bidirectional remains unclear to date. OBJECTIVE:To explore the temporal rel...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.120.317950
更新日期:2020-12-04 00:00:00
abstract::Previous work has shown that neutrophils isolated from whole blood adhere to cardiac-myocytes via CD18 (beta 2 integrin) to cause injury to the heart cells. In vitro, we have found that upon endothelial transmigration, neutrophils can also express alpha 4 beta 1; however, whether this contributes to neutrophil adhesio...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.81.2.196
更新日期:1997-08-01 00:00:00
abstract::Experiments were performed to investigate whether balloon injury induces nitric oxide synthase activity in the blood vessel wall. Contractions to phenylephrine were compared in left carotid arteries of the rat, previously injured by balloon catheterization and excised either immediately (t = 0), 6, or 24 hours after t...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.71.2.331
更新日期:1992-08-01 00:00:00
abstract::Cardiovascular aging is associated with decreased endothelial vasoreactivity and prolonged diastolic relaxation. As diminished NO signaling contributes to age-associated endothelial dysfunction, we tested the hypothesis that impaired NO signaling or bioactivity also contributes to slowed ventricular relaxation with ag...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.88.1.97
更新日期:2001-01-19 00:00:00
abstract::We report the cloning of cDNAs encoding two different human nonmuscle myosin heavy chains designated NMMHC-A and NMMHC-B. The mRNAs encoding NMMHC-A and NMMHC-B are both 7.5 kb in size but are shown to be the products of different genes, which are localized to chromosome 22q11.2 and chromosome 17q13, respectively. In ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.69.2.530
更新日期:1991-08-01 00:00:00
abstract::MicroRNAs (miRNAs) are a recently discovered class of endogenous, small, noncoding RNAs that regulate about 30% of the encoding genes of the human genome. However, the role of miRNAs in vascular disease is currently completely unknown. Using microarray analysis, we demonstrated for the first time that miRNAs are aberr...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.106.141986
更新日期:2007-06-08 00:00:00
abstract::Angiotensin II exerts positive inotropic and chronotropic effects on the mammalian heart by binding to specific membrane receptors. Recently, two subtypes of angiotensin II receptors (AT1 and AT2) have been distinguished by using the nonpeptide antagonists losartan (previously known as DuP 753) and PD123177. To evalua...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.71.6.1482
更新日期:1992-12-01 00:00:00
abstract:RATIONALE:PCSKs (Proprotein convertase subtilisins/kexins) are a protease family with unknown functions in vasculature. Previously, we demonstrated PCSK6 upregulation in human atherosclerotic plaques associated with smooth muscle cells (SMCs), inflammation, extracellular matrix remodeling, and mitogens. OBJECTIVE:Here...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.119.316063
更新日期:2020-02-28 00:00:00
abstract::Previous studies have shown that cardiac endothelial cells release substances that influence myocardial contraction. Since PO2 is an important stimulus that modulates endothelial function, we investigated the effects of acute moderate hypoxia and reoxygenation on the release of cardioactive factors by endothelial cell...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.80.5.688
更新日期:1997-05-01 00:00:00
abstract::Two NO synthase (NOS) isoforms have been described in vessels, an endothelial constitutive NOS (eNOS) and an inducible NOS (iNOS). The purpose of the present study was to examine the endothelium-dependent and endothelium-independent hypotensive response in aging rats, analyzing the ability of their vessels to produce ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.83.3.279
更新日期:1998-08-10 00:00:00
abstract::Contraction and relaxation of vascular smooth muscle and cardiac myocytes are key physiological events in the cardiovascular system. These events are regulated by second messengers, cAMP and cGMP, in response to extracellular stimulants. The strength of signal transduction is controlled by intracellular cyclic nucleot...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.RES.0000256354.95791.f1
更新日期:2007-02-16 00:00:00
abstract::Fibroblast growth factor-1 (FGF-1), a prototype member of the heparin-binding growth factor family, is a potent mitogen for vascular endothelial cells and a variety of other cell types. FGF-1 can induce the expression of the platelet-derived growth factor-A chain (PDGF-A) gene in endothelial cells; however, the underl...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.81.2.282
更新日期:1997-08-01 00:00:00