MicroRNA: Novel Regulators Involved in the Remodeling and Reverse Remodeling of the Heart

Wang, Jue; Xu, Rui‐Xia; Lin, Fei; Zhang, Shiju; Zhang, Gang; Hu, Shengshou; Zheng, Zhe

doi:10.1159/000172616

Cited by 44 publications

(30 citation statements)

References 56 publications

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“…miR-92 plays a role in heart failure (58), and miR-15 has been implicated in cardiovascular disorders (15). Myocardial expression of miR-27b is increased during heart development (9), and miR-29a plays an important role in heart remodeling and reverse remodeling (66). However, the role of these miRs in vascular biology is yet to be determined.…”

Section: Discussionmentioning

confidence: 99%

Implication of microRNAs in atrial natriuretic peptide and nitric oxide signaling in vascular smooth muscle cells

Kotlo

Hesabi

Danziger³

2011

American Journal of Physiology-Cell Physiology

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Kotlo KU, Hesabi B, Danziger RS. Implication of microRNAs in atrial natriuretic peptide and nitric oxide signaling in vascular smooth muscle cells. Am J Physiol Cell Physiol 301: C929 -C937, 2011. First published July 6, 2011; doi:10.1152/ajpcell.00088.2011 are endogenous small RNA molecules that suppress gene expression by binding to complementary sequences in the 3= untranslated regions of their target genes. miRs have been implicated in many diseases, including heart failure, ischemic heart disease, hypertension, cardiac hypertrophy, and cancers. Nitric oxide (NO) and atrial natriuretic peptide (ANP) are potent vasorelaxants whose actions are mediated through receptor guanylyl cyclases and cGMP-dependent protein kinase. The present study examines miRs in signaling by ANP and NO in vascular smooth muscle cells. miR microarray analysis was performed on human vascular smooth muscle cells (HVSMC) treated with ANP (10 nM, 4 h) and S-nitroso-N-acetylpenicillamine (SNAP) (100 M, 4 h), a NO donor. Twenty-two shared miRs were upregulated, and 21 shared miRs were downregulated, by both ANP and SNAP (P Ͻ 0.05). Expression levels of four miRs (miRs-21, -26b, -98, and -1826), which had the greatest change in expression, as determined by microarray analysis, were confirmed by quantitative RT-PCR. Rp-8-Br-PET-cGMPS, a cGMPdependent protein kinase-specific inhibitor, blocked the regulation of these miRs by ANP and SNAP. 8-bromo-cGMP mimicked the effect of ANP and SNAP on their expression. miR-21 was shown to inhibit HVSMC contraction in collagen gel lattice contraction assays. We also identified by computational algorithms and confirmed by Western blot analysis new intracellular targets of miR-21, i.e., cofilin-2 and myosin phosphatase and Rho interacting protein. Transfection with pre-miR-21 contracted cells and ANP and SNAP blocked miR-21-induced HVSMC contraction. Transfection with anti-miR-21 inhibitor reduced contractility of HVSMC (P Ͻ 0.05). The present results implicate miRs in NO and ANP signaling in general and miR-21 in particular in cGMP signaling and vascular smooth muscle cell relaxation. guanosine 3=,5=-cyclic monophosphate miR-21 MICRORNAS (MIRS) HAVE EMERGED as a novel class of endogenous small RNA molecules that negatively regulate ϳ30% of genes in the cell by annealing with complementary sequences in the 3= untranslated regions of their target mRNAs. More than 1,000 miRs have been identified in the human genome. A single miR can regulate hundreds of functional targets, and, similarly, a single mRNA can be targeted by multiple miRs in a cell (2). Recent evidence suggests roles for miRs in diverse processes including cell differentiation and proliferation (3,19,22). Aberrant expression of miRs has been linked to developmental abnormalities and pathologies, including cardiac hypertrophy, hypertension, ischemic heart disease, heart failure, and cancers (8,24,33,56,68,69).The potential role of miRs in vascular smooth muscle cell (VSMC) biology and blood pressure is just beginning to be appreciated. Both miR-143...

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Section: Discussionmentioning

confidence: 99%

Implication of microRNAs in atrial natriuretic peptide and nitric oxide signaling in vascular smooth muscle cells

Kotlo

Hesabi

Danziger³

2011

American Journal of Physiology-Cell Physiology

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“…Both have been demonstrated to regulate heart development [4,5,6], and both have been demonstrated to be dysregulated in the hypertrophic and failing hearts [7,8,9]. Another cardiac-specific miRNA has been identified, miR-208 , which is believed to play an important role in response to stress, such as pressure overload, activated calcineurin, or hypothyroidism [10].…”

Section: Introductionmentioning

confidence: 99%

MicroRNAs miR-1, miR-133a, miR-133b and miR-208 Are Dysregulated in Human Myocardial Infarction

Boštjančič

Zidar²,

Štajer³

et al. 2009

Cardiology

276

192

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Objectives: MicroRNAs (miRNAs) are noncoding single-stranded RNA molecules that regulate gene expression in physiological functions, development and disease. In recent studies, three miRNAs have been described as muscle or cardiac specific: miR-1, miR-133, and miR-208, being involved in heart development and disease; but there are limited data on their role in human myocardial infarction (MI). We therefore analyzed their expression in human MI. Methods: Autopsy samples of infarcted heart tissue from 50 patients with MI, 8 healthy trauma victims and 9 fetuses that died in utero were included. miRNAs miR-1, miR-133a/b and miR-208 were analyzed using quantitative real-time polymerase chain reaction. Results:miR-208 was upregulated, whereas miR-1 and miR-133a were downregulated in MI compared to healthy adult and fetal hearts. All four tested miRNAs were downregulated in fetal hearts compared to healthy adult hearts. Conclusions: Our study showed the involvement of muscle- and/or cardiac-specific miRNAs miR-1, miR-133a/b and miR-208 in human MI. The most significant finding was upregulation of miR-208 and downregulation of miR-1 and miR-133a in MI compared to healthy adult hearts. Some patterns of miRNA expression were similar in MI and fetal hearts, supporting the concept of cardiac gene reprogramming in the remodeling of the heart.

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“…32 Furthermore, microRNA-24 downregulation has been found to be associated with fibrosis in hypertrophic hearts. 33 Further studies are required to elucidate the potential contribution of furin in collagen alterations of HF patients.…”

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confidence: 99%

Collagen Cross-Linking But Not Collagen Amount Associates With Elevated Filling Pressures in Hypertensive Patients With Stage C Heart Failure

et al. 2012

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Abstract-We investigated whether the quality of myocardial collagen associates with elevated left-sided filling pressures in 38 hypertensive patients with stage C chronic heart failure. Filling pressures were assessed invasively measuring pulmonary capillary wedge pressure. Left ventricular chamber stiffness constant was calculated from the deceleration time of the early mitral filling wave. The fraction of myocardial volume occupied by total collagen tissue and collagen type I fibers was assessed histomorphologically. The degree of collagen cross-linking (CCL), which determines the formation of insoluble stiff collagen, was assessed by colorimetric and enzymatic procedures. Key Words: collagen Ⅲ filling pressures Ⅲ heart failure A rterial hypertension has been long considered as one of the most common etiologic conditions predisposing to heart failure (HF).1 Furthermore, a recent systematic review shows that HF development remains a major problem in treated hypertensive patients.2 It has been shown that myocardial fibrosis, a common finding in postmortem studies and endomyocardial biopsies of patients with hypertensive heart disease (HHD), 3 is associated with the increase of left ventricular (LV) chamber stiffness 4,5 and the development of clinically overt HF in these patients. 6,7 It has been proposed that the increase in LV stiffness can contribute to compromised diastolic function and elevate left-sided filling pressures (FPs) in hypertensive patients. 8 The definition of myocardial fibrosis is based on the quantification of an excess of collagen fiber deposition, as assessed by staining techniques. However, it must be considered that collagen-dependent LV chamber stiffness is influenced not only by the amount of collagen fibers but also by their qualitative properties (ie, the degree of collagen crosslinking [CCL] among collagen fibrils that determines the insolubility, stiffness, and resistance to degradation of the resulting fibers; the relative proportions of collagen types I and III fibers; and the diameter of the collagen fibers and their spatial alignment). 9 In fact, as demonstrated in different experimental models of pressure overload, although LV chamber stiffness is affected by changes in both collagen

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MicroRNA: Novel Regulators Involved in the Remodeling and Reverse Remodeling of the Heart

Cited by 44 publications

References 56 publications

Implication of microRNAs in atrial natriuretic peptide and nitric oxide signaling in vascular smooth muscle cells

Implication of microRNAs in atrial natriuretic peptide and nitric oxide signaling in vascular smooth muscle cells

MicroRNAs<i> miR-1</i>,<i> miR-133a, miR-133b </i>and <i>miR-208</i> Are Dysregulated in Human Myocardial Infarction

Collagen Cross-Linking But Not Collagen Amount Associates With Elevated Filling Pressures in Hypertensive Patients With Stage C Heart Failure

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