Abstract:
:MicroRNAs act as negative regulators of gene expression by inhibiting the translation or promoting the degradation of target mRNAs. Because individual microRNAs often regulate the expression of multiple target genes with related functions, modulating the expression of a single microRNA can, in principle, influence an entire gene network and thereby modify complex disease phenotypes. Recent studies have identified signature expression patterns of microRNAs associated with pathological cardiac hypertrophy, heart failure, and myocardial infarction in humans and mouse models of heart disease. Gain- and loss-of-function studies in mice have revealed profound and unexpected functions for these microRNAs in numerous facets of cardiac biology, including the control of myocyte growth, contractility, fibrosis, and angiogenesis, providing glimpses of new regulatory mechanisms and potential therapeutic targets for heart disease. Especially intriguing is the discovery of a network of muscle-specific microRNAs embedded within myosin heavy chain genes, which control myosin expression and the response of the heart to stress and thyroid hormone signaling. Disease-inducing cardiac microRNAs can be persistently silenced in vivo through systemic delivery of antimiRs, allowing for the direct therapeutic modulation of disease mechanisms. Here, we summarize current knowledge of the roles of miRNAs in heart disease and consider the advantages and potential challenges of microRNA-based approaches compared to conventional drug-based therapies.
journal_name
Circ Resjournal_title
Circulation researchauthors
van Rooij E,Marshall WS,Olson ENdoi
10.1161/CIRCRESAHA.108.183426subject
Has Abstractpub_date
2008-10-24 00:00:00pages
919-28issue
9eissn
0009-7330issn
1524-4571pii
103/9/919journal_volume
103pub_type
杂志文章,评审abstract::Activin is a member of the transforming growth factor-beta superfamily, and it modulates the proliferation and differentiation of various target cells. In this study, we investigated the role of activin in the initiation and progression of human atherosclerosis. The expression of activin, its physiological inhibitor f...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.85.10.931
更新日期:1999-11-12 00:00:00
abstract::Adenosine modulates a variety of cellular functions by interacting with specific cell surface G protein-coupled receptors (A1, A2A, A2B, and A3) and is a potential mediator of angiogenesis through the A2B receptor. The lack of a potent, selective A2B receptor inhibitor has hampered its characterization. Our goal was t...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000091260.78959.BC
更新日期:2003-09-19 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000224120.52792.10
更新日期:2006-06-09 00:00:00
abstract::Nuclear factor kappa B (NF-kappaB) participates in hypertension-induced vascular and target-organ damage. We tested whether or not endothelial cell-specific NF-kappaB suppression would be ameliorative. We generated Cre/lox transgenic mice with endothelial cell-restricted NF-kappaB super-repressor IkappaBalphaDeltaN (T...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.107.150474
更新日期:2007-08-03 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.86.2.233
更新日期:2000-02-04 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.86.11.1173
更新日期:2000-06-09 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.118.311378
更新日期:2018-09-14 00:00:00
abstract::Increasing evidence suggests that endogenous NO inhibits sympathetic outflow in anesthetized animals. However, in a recent study from this laboratory, we were unable to find any evidence of increased renal sympathetic nerve activity (RSNA) in response to blockade of NO synthesis in conscious rabbits. Because angiotens...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.82.4.496
更新日期:1998-03-09 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.63.6.1020
更新日期:1988-12-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/hh2301.100349
更新日期:2001-11-23 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000180663.42594.aa
更新日期:2005-09-02 00:00:00
abstract::Nitric oxide (NO) functions principally as a diffusible paracrine effector. The exception is in cardiomyocytes where both NO synthases (NOS) and target proteins coexist, allowing NO to work in an autocrine/intracrine fashion. However, the most abundant myocyte isoform (NOS3) is far more expressed in vascular endotheli...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000119323.79644.20
更新日期:2004-03-19 00:00:00
abstract::To determine if intestinal microvascular growth is impaired in diabetic juvenile animals, a segment of the terminal ileum was marked and the microvasculature of this segment observed at the age of 5 weeks and again at the age of 10-11 weeks in normal and diabetic Sprague Dawley rats. Diabetes was induced by streptozot...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.63.2.429
更新日期:1988-08-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.64.4.806
更新日期:1989-04-01 00:00:00
abstract::We carried out a systematic study on the effects of elevating [K]o on the properties of a transient outward potassium channel encoded by a cardiac cDNA (RHK1) and compared them with those on two Shaker potassium channels (H-4 and H-37). The amino acid sequences of all three channels are known, and their structure-func...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.71.3.657
更新日期:1992-09-01 00:00:00
abstract::Voltage-gated K(+) channels (Kv) play a critical role in regulating arterial tone by modulating the membrane potential of vascular smooth muscle cells. Our previous work demonstrated that the dominant 4-aminopyridine (4-AP)-sensitive, delayed rectifier Kv current of rabbit portal vein (RPV) myocytes demonstrates simil...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh2301.100817
更新日期:2001-11-23 00:00:00
abstract::Urea transporters have been cloned from kidney medulla (UT-A) and erythrocytes (UT-B). We determined whether UT-A proteins could be detected in heart and whether their abundance was altered by uremia or hypertension or in human heart failure. In normal rat heart, bands were detected at 56, 51, and 39 kDa. In uremic ra...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh1401.093293
更新日期:2001-07-20 00:00:00
abstract::The present study was undertaken to determine the mechanism of neointima formation in rabbit arteries subjected to extensive endothelial desquamation. Endothelial cells were selectively removed from the abdominal aorta by passing an inflated balloon catheter through the vessel. The healing response was then studied se...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.36.1.58
更新日期:1975-01-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.111.247924
更新日期:2012-08-17 00:00:00
abstract:RATIONALE:Shear stress (SS) has an established role in atherosclerotic plaque localization, but how it exerts its protective effect is not fully understood. OBJECTIVE:To test the hypothesis that SS may downregulate angiotensin type 1 receptors (AT(1)Rs). Angiotensin II has been shown to be proinflammatory and to promo...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.204040
更新日期:2009-10-23 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.RES.0000163634.51301.0d
更新日期:2005-05-13 00:00:00
abstract::Acetylcholine (ACh) evokes the conduction of vasodilation along resistance microvessels. However, it is not known which cell layer (endothelium or smooth muscle) serves as the conduction pathway. In isolated, cannulated feed arteries ( approximately 70 microm in diameter at 75 mm Hg; length approximately 4 mm) of the ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.86.1.94
更新日期:2000-01-07 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.39.6.860
更新日期:1976-12-01 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::Because phospholemman (PLM) regulates the Na(+)/K(+) pump (NKA) and is a major cardiac phosphorylation target for both protein kinase A (at Ser68) and protein kinase C (PKC) (at both Ser63 and Ser68), we evaluated whether PLM mediates the PKC-dependent regulation of NKA function and protein kinase A/PKC crosstalk in v...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000251667.73461.fb
更新日期:2006-12-08 00:00:00
abstract::The mechanical properties of mammalian ventricular cardiac muscle have been studied in the presence and in the absence of an intact endocardial surface. Isotonic and isometric twitch contractions were obtained from papillary muscles of the right ventricle of cat at 29 degrees and 37 degrees C, at different extracellul...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.62.2.358
更新日期:1988-02-01 00:00:00
abstract:RATIONALE:Endothelial colony forming cells (ECFCs) or late blood outgrowth endothelial cells can be isolated from human cord or peripheral blood, display properties of endothelial progenitors, home into ischemic tissues and support neovascularization in ischemic disease models. OBJECTIVE:To assess the functions of CYT...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.118.313645
更新日期:2019-01-18 00:00:00
abstract:RATIONALE:Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor-β super family of secreted factors. A recent study showed that reduced GDF11 blood levels with aging was associated with pathological cardiac hypertrophy (PCH) and restoring GDF11 to normal levels in old mice rescued PCH. ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.115.307527
更新日期:2015-11-06 00:00:00
abstract::We examined the late coronary vascular response to carotid chemoreceptor reflex activation in normal, conscious dogs instrumented for the measurement of right main and left circumflex coronary artery blood flows, arterial and right ventricular pressures, and arterial and coronary sinus blood gases and O2 contents. Wit...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.54.1.96
更新日期:1984-01-01 00:00:00
abstract::It has been proposed that lipopolysaccharide (LPS) bound to the 60-kD LPS binding protein (LBP) forms an LPS/LBP complex that, in turn, binds to the CD14 receptor on monocytes/macrophages and stimulates the release of cytokines. We examined the role of LBP and CD14 in tumor necrosis factor-alpha (TNF-alpha) production...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.73.1.15
更新日期:1993-07-01 00:00:00