Cardio 9 Flashcards Preview

FRONTIERS IN PHYSIOLOGY > Cardio 9 > Flashcards

Flashcards in Cardio 9 Deck (20):
1

What are miRNAs?

Short, non-coding RNA molecules, involved in many biological processes

2

Where do miRNAs bind?

Complementary 3’UTR of multiple target mRNAs (seed)

3

What is the seed region?

8bp long is complementary to a target region of the mRNA - causes mRNA degradation - human diseases

4

What does dicer do?

Makes miRNAs in mice hearts

5

What happens if dicer is absent?

Mice without dicer had an enlarged heart - heart pathology - hearts were dilates (thin walls) - dilated cardiomyopathy (heart disease), impaired pump ability, premature death

6

What is heart failure?

Heart failure occurs when the heart muscle has become too weak to pump blood through the body as effectively as normal – common endpoint for CVD and causes breathlessness and hinders day-day activities

7

What are the features of PI3K?

- PI3K is cardioprotective. Protects from cardiac disease, dysfunction and failure
- Prevents excessive heart growth, heart dysfunction and fibrosis
- PI3K activity increased (physiological hypertrophy) - subjected to MI - generate a spectrum of heart phenotypes

8

When are miR-34 and miR-652 increased and reduced?

Reduced in physiologic hypertrophy and increased in diseased heart

9

What does miR-34 cause?

Heart attack, tumour progression

10

What are the features of luciferase?

Enzyme produced by fireflies - can be used to validate targets - luciferase emits light if there is no binding and if there is binding there will be reduced light and luciferase

11

What do miRNA spinges contain?

Multiple miRNA binding sites which act as competitive inhibitors for miRNA binding
- Sponges are designed to include 4-10 multiple binding sites to sequester miRNAs

12

How many binding sites in sponges?

4-10

13

What are the features of AAV6?

AAV6 – transduces heart and skeletal muscle in combination with CMV promoter. 4nt spacer to optimise binding and reduce formation of secondary structures

14

What are the features of LNA-antimiRs (miRNA inhibitors)?

Chemically modified antisense oligonucleotides that can inhibit miRNAs (bind to them to stop them interrupting mRNA)

High binding affinity, stable, no delivery vehicle, easy formulation in saline, negligible off-target effects, no evidence of toxicity, chronic knockdown

15

What does antimir (miR-652) reduce?

-miRNA expression
-Heart, lung and atria size
-Fibrosis
-Anp (diseased heart state)
-Cell size
-Cell death
-Bax (apoptosis)
-Inflammation
-luciferase (accurate)

16

What does antimir (miR-652) improve?

-Electrical function
-Repair and regeneration
-Gene expression
-Cardiac function
-Coronary angiogenesis
-JAG1 (anti hypertrophic)

17

What is the role of vinculin?

Cardiomyocyte stability, regulates expression of proteins in the intercalated disk

18

Although LNA inhibitors are not specific, do they have an effect on organ weight?

No

19

What are the pathways for physiological and pathological hypertrophy?

Physiological: IGF-1, Akt, PI3K
Pathological: GPCR

20

What are the key regulators of skeletogenesis?

miR-34b miR-34c