Cardiac Hypertrophy Flashcards
What is volume overload?
An excessive EDV that leads to an increase in stroke volume
What is pressure overload?
An excessive pressure in the ventricles outflow tract (afterload) that leads to a decrease in stroke volume if the left ventricle is affected.
How does cardiac output stay the same if pressure/volume overload affects stroke volume?
Because the heart adjusts the heart rate to maintain a constant cardiac output.
What is the long term effect of pressure/volume overload?
Hypertrophy and heart failure because the heart is unable to compensate for the changes anymore.
Physiological hypertrophy refers to?
Cardiac cells increasing proportionally in length and width
Eccentric hypertrophy refers to?
Cardiac cells increasing unproportionally in length more so than width
Concentric hypertrophy refers to?
Cardiac cells increasing unproportionally in width more so than length
What are some other factors aside from pressure or volume overload that many cause hypertrophy?
Hypertrophic factors, increases in [Ca2+]i, and mechanical forces.
What are the 8 hypertrophic factors that can cause hypertrophy?
- Cytosolic protein myotrophin (Myo/V1)
- Cytokine cardiotrophin (CT-1)
- Catecholamines
- Angiotensin II
- Endothelin 1
- Insulin-like growth factor 2 (IGF-2)
- Transforming growth factor-beta (TGF-beta)
- Interleukin 1 (IL-1)
What do catecholamines and angiotensin II do to trigger hypertrophy?
Activate the MAPK pathway
What is the transcriptional response to hypertrophic stimuli?
Activation of the following transcription factors:
- Zinc finger GATA4
- SRF
- Sp1
- TEF-1
During initial pressure and volume overload, what does elevated intracellular calcium do?
Calcium activates calcineurin.
What exactly is calcineurin?
A calcium-dependent phosphotase
What does calcineurin do once activated?
It dephosphorylates NF-AT3 which then binds to GATA4 which activates genes responsible for hypertrophy.
What is the mechanical sensor that stimulates hypertrophy?
Muscle LIM Protein (MLP)
