MicroRNA Therapeutics for Cardiac Disease

Tang, Yaoping; Poteh, Ndah A; Chiang, Angela; Kim, Il-man

doi:10.4172/2329-6607.1000e113

Cited by 3 publications

(3 citation statements)

References 26 publications

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“…MicroRNAs (or miRNAs) are small (18–25 nucleotides), single‐stranded, noncoding RNAs that repress translation of mRNAs by binding to imperfectly complementary‐specific mRNA sequences . The miRNAs that have been found to be critical for heart function are involved in vascular remodeling, coronary artery disease, and heart failure .…”

Section: Small Molecule Tyrosine Kinase Inhibitor‐induced Cardiovascumentioning

confidence: 99%

Cardiovascular Toxicities of Small Molecule Tyrosine Kinase Inhibitors: An Opportunity for Systems‐Based Approaches

Brown

Nhola

Herrmann

2016

Clin Pharma and Therapeutics

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Once universally considered a rapidly fatal condition, cancer has increasingly become a chronic medical condition and comorbidities and adverse effects of cancer therapies have become increasingly significant. One of the leading advancements that has gained traction for the treatment of a variety of malignancies is the class of small molecule tyrosine kinase inhibitors (TKIs). Although, in many aspects revolutionary, TKIs have their own profile of side effects, including cardiovascular side effects, the most common being hypertension (HTN), congestive heart failure, corrected QT (QTc) prolongation, and instances of premature coronary heart disease. Herein, we describe the mechanisms of small TKI-induced cardiovascular toxicity and related intracellular signaling. In particular, systems-based approaches to the understanding of small TKI-induced cardiovascular toxicity are addressed. The pathophysiology of synergic cardiovascular toxicity from TKIs, anthracyclines, and monoclonal antibodies (e.g., trastuzumab, bevacizumab) is illustrated. Finally, recommendations are made for implementing systems medicine in clinical practice, for individualized cardiovascular wellness after cancer therapy.

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Section: Small Molecule Tyrosine Kinase Inhibitor‐induced Cardiovascumentioning

confidence: 99%

Cardiovascular Toxicities of Small Molecule Tyrosine Kinase Inhibitors: An Opportunity for Systems‐Based Approaches

Brown

Nhola

Herrmann

2016

Clin Pharma and Therapeutics

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“…This shows the future hope of miRNAs as biomarkers [42,43]. Based on recent data obtained miRNAs act as intercellular and intracellular mediator in cardiac diseases could be considered as prognostic biomarker, moreover, the potential usefulness of cardiomyocyte-enriched miRNA as diagnostic marker in acute coronary syndrome and the contribution of miRNAs (miR-21) as target in heart failure resulting in novel therapeutic strategies [44][45][46].…”

Section: Clinical Significance Of Mirnasmentioning

confidence: 94%

MicroRNA: A Target Candidate to Turn the Tide

Rao¹

2015

Mol Biol

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Understanding the molecular basis of life is at the centre today, the integration of Computer Science, Mathematics and statistics improved the belief in structural and functional genomics. Recently there is an increased interest in function of non-coding RNA transcripts. Non-coding RNAs are small molecules that are not translated into proteins, but these molecules have a pivotal role in almost all molecular and cellular processes. MicroRNA is one of those noncoding RNA molecules that regulate gene expression at posttranslational level. These 18-25 nt length molecules are primary transcribes consist of a secondary hairpin structure. There are 700 miRNAs in the human genome, at least 1-4% of expressed genes; this makes miRNAs as the biggest group of regulators. This review summarizes biogenesis, role of expression profiles in and at various cellular and molecular mechanisms and their applications. More or less, research on non-coding RNA candidates has been done and proved their importance, however, even more to be proved.

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“…Micro-ribonucleic acids (miRNAs) have been reported to have an impact on the pathogenesis of cardiac diseases [ 7 , 8 ] and recent evidence has indicated that miRNAs participate in the development and progression of cardiovascular diseases [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. However, miRNAs should be fully exploited—how their targets functionally interact with and are simultaneously regulated by multiple miRNAs.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA Let-7a, -7e and -133a Attenuate Hypoxia-Induced Atrial Fibrosis via Targeting Collagen Expression and the JNK Pathway in HL1 Cardiomyocytes

Yang

et al. 2022

IJMS

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Fibrosis is a hallmark of atrial structural remodeling. The main aim of this study was to investigate the role of micro-ribonucleic acids (miRNAs) in the modulation of fibrotic molecular mechanisms in response to hypoxic conditions, which may mediate atrial fibrosis. Under a condition of hypoxia induced by a hypoxia chamber, miRNA arrays were used to identify the specific miRNAs associated with the modulation of fibrotic genes. Luciferase assay, real-time polymerase chain reaction, immunofluorescence and Western blotting were used to investigate the effects of miRNAs on the expressions of the fibrotic markers collagen I and III (COL1A, COL3A) and phosphorylation levels of the stress kinase c-Jun N-terminal kinase (JNK) pathway in a cultured HL-1 atrial cardiomyocytes cell line. COL1A and COL3A were found to be the direct regulatory targets of miR-let-7a, miR-let-7e and miR-133a in hypoxic atrial cardiac cells in vitro. The expressions of COL1A and COL3A were influenced by treatment with miRNA mimic and antagomir while hypoxia-induced collagen expression was inhibited by the delivery of miR-133a, miR-let-7a or miR-let-7e. The JNK pathway was critical in the pathogenesis of atrial fibrosis. The JNK inhibitor SP600125 increased miRNA expressions and repressed the fibrotic markers COL1A and COL3A. In conclusion, MiRNA let-7a, miR-let-7e and miR-133a play important roles in hypoxia-related atrial fibrosis by inhibiting collagen expression and post-transcriptional repression by the JNK pathway. These novel findings may lead to the development of new therapeutic strategies.

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MicroRNA Therapeutics for Cardiac Disease

Cited by 3 publications

References 26 publications

Cardiovascular Toxicities of Small Molecule Tyrosine Kinase Inhibitors: An Opportunity for Systems‐Based Approaches

Cardiovascular Toxicities of Small Molecule Tyrosine Kinase Inhibitors: An Opportunity for Systems‐Based Approaches

MicroRNA: A Target Candidate to Turn the Tide

MicroRNA Let-7a, -7e and -133a Attenuate Hypoxia-Induced Atrial Fibrosis via Targeting Collagen Expression and the JNK Pathway in HL1 Cardiomyocytes

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