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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
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Systolic Heart Failure and Compensatory MechanismsSystolic heart failure (also termed HFrEF, Heart Failure with Reduced Ejection Fraction) is the most prevalent type of heart filure. It results in a decreased volume of blood being pumped from the ventricle. The aortic arch and carotid sinuses have baroreceptors that detect reduced blood pressure, triggering the sympathetic nervous system (SNS) to release epinephrine and norepinephrine. Initially, this response aims to boost heart rate and...
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Heart failure (HF) is a progressive syndrome involving ventricles that leads to inadequate cardiac output. It can be classified based on location and output or ejection fraction. Ejection fraction (EF) is an essential measurement in the diagnosis and surveillance of HF. Reduced EF corresponds to systolic heart failure (HFrEF). However, HF with preserved ejection fraction (HFpEF) is becoming increasingly prevalent. Also known as diastolic HF, this form of HF is related to aging. The...
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Heart failure refers to a clinical syndrome caused by structural or functional cardiac disorders that prevent the heart from pumping an adequate amount of blood to meet the body's metabolic needs. This condition often arises from myocardial infarction or ischemia, leading to decreased cardiac output, reduced tissue perfusion, impaired gas exchange, fluid volume imbalance, and decreased functional ability.Heart failure can result from disruptions in the mechanisms that regulate cardiac output...
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Heart Failure VI: Adjunct Therapies01:22

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Additional therapies for treating patients with heart failure (HF) may include procedural interventions, supplemental oxygen, the management of sleep disorders, and nutritional therapy.Procedural InterventionsImplantable Cardioverter-Defibrillator: For patients at risk of life-threatening arrhythmias due to severe left ventricular dysfunction, an Implantable Cardioverter-Defibrillator (ICD) can detect and terminate these arrhythmias, preventing sudden cardiac death and improving survival rates.
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Heart failure and kidney perfusion are interconnected in a complex way. Reduced renal perfusion and venous congestion are two significant factors that contribute to renal dysfunction in heart failure. The kidneys, primarily responsible for fluid balance in the body, are adversely affected due to compromised cardiac output and increased venous pressure. In response to reduced renal perfusion, the kidneys activate neurohumoral mechanisms to restore balance. However, these mechanisms can be...
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Functional Screening Identifies MicroRNAs as Multi-Cellular Regulators of Heart Failure.

Robin Verjans1,2, Wouter J A Derks1,2, Kerstin Korn2

  • 1Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6200 MD, Maastricht, Limburg, The Netherlands.

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|April 17, 2019
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Summary
This summary is machine-generated.

MicroRNAs (miRNAs) are key regulators in heart failure (HF). This study found that specific miRNAs control multiple cell types, impacting cardiac hypertrophy, fibrosis, and inflammation, offering new therapeutic targets for HF.

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Area of Science:

  • Cardiovascular Biology
  • Molecular Biology
  • MicroRNA Research

Background:

  • Heart failure (HF) is a major cause of death, driven by cardiac hypertrophy, fibrosis, and inflammation.
  • MicroRNAs (miRNAs) regulate these pathological processes, but their multicellular roles in cardiac disease are understudied.

Purpose of the Study:

  • To investigate the multicellular regulatory functions of 194 differentially expressed miRNAs in cardiac inflammatory disease.
  • To identify miRNAs that modulate cardiomyocyte size, fibroblast collagen production, and macrophage polarization.

Main Methods:

  • Screening of 194 miRNAs for their effects on cardiomyocyte size, fibroblast collagen production, and macrophage polarization.
  • In vitro analysis of miRNA-mediated changes in gene and protein expression related to cardiac pathophysiology.
  • Identification of specific miRNAs regulating fibrosis and macrophage activation.

Main Results:

  • 13% of tested miRNAs modulated cardiomyocyte size, 26% modulated fibroblast collagen production, and 41% modulated macrophage polarization.
  • Seventeen miRNAs influenced all three cellular processes, including miR-210 and miR-145-3p.
  • New roles were identified for miRNAs, including miR-145-3p and miR-891a-3p in fibrosis, and miR-223-3p, miR-486-3p, and miR-488-5p in macrophage polarization.

Conclusions:

  • MicroRNAs act as multicellular regulators in cardiac disease, affecting hypertrophy, fibrosis, and inflammation.
  • This study identified novel miRNA functions and attributed new cellular effects to known miRNAs, highlighting their potential as therapeutic targets.