Cardiovascular Health 3.3 (Heart): New Frontiers in micro RNA therapies Flashcards
Are miRNAs associated with disease?
Yes.
What are miRNAs?
Short RNA strands that arent involved in protein production.
Where do miRNAs bind?
To the 3’ complementary region of mRNA, at the seed region.
What is the effect of miRNA binding to mRNA?
Can cause mRNA degredation or protein synthesis inhibition.
Can one miRNA target more than one mRNA?
Yes, hundreds.
Can many miRNAs target the same mRNA?
Yes.
What happens when the Dicer gene is deleted? Is there a cure?
Heart is enlarged in its absence, thin walls, poor blood pumping and premature death.
No cure, treatment slows progression.
What happens when miRNAs are disregulated?
A disease.
What is pathological hypertrophy?
Occurs when a diseased, such as high blood pressure. Increases fibrosis and apoptosis.
What is physiological hypertrophy?
Is cardioprotective, with no apoptosis or fibrosis.
Associated with good heart function.
Is PI3K cardioprotective?
Yes.
What happens when PI3K is up/downregulated?
When subject to a heart disease, upregulated PI3K hearts were cardioprotected.
Downregulated hearts were more susceptible to pathology.
What effects does PI3K have on heart pathology?
Prevents fibrosis, excessive heart growth, and heart dysfunction.
How can a cardiovascular disease be treated via PI3K?
Associated miRNA needs to be found.
How can the PI3K miRNA be found?
Obtain a spectrum of heart tissue, with varying heart pathology.
Use microarray to find miRNA.
When using microarrays to find miRNA associated with PI3K, what must its levels be in healthy vs damaged heart tissue?
Low in healthy, but high in susceptible and damaged heart tissue.
Once miRNAs are found, what must be done to treat the cardiovascular disease?
Block them using miRNA blockers.
How can miRNA blocker effeciveness be evaluated?
Induce pressure overload heart failure.
What happens to miRNA after delivering? Are they stable when delivered?
Turn into locked nucleic acids.
Stable, no need for vectors.
Are miRNAs toxic?
No.
What effect did miRNA blockers have?
Prevented heart growth and improved function and weight.
How can luciferase be used for target validation?
A plasmid vector is used to carry the miRNA and target plasmid.
When they arent bound, luciferase activity present, decreased activity when they bind.
Photometer used to evaluate.
Are miRNA blockers (lna inhibitors) tissue specific?
No.
Do miRNA blockers associated with caridovascular diseases affect other organs? What is a potential consequence?
No,doesn’t affect their weight, and their morphology appears normal. Are involved in anti-tumour mechanisms however, blocking systemically could lead to oncogenesis. Also associated with healthy brain function.
