Heart failure and hypertrophy

Question 1

How does the heart respond to chronic stress

Answer 1

altered size and shape: dilation (due to MI), hypertrophy

Question 2

Describe two types of hypertrophy

Answer 2

Pathological: myocyte length increases less than myocyte width increases, fibrosis and cardiac dysfunction. Physiological: myocyte length increases more than myocyte width increases, no fibrosis and no cardiac dysfunction

Question 3

What causes pathological hypertrophy? Physiological hypertrophy?

Answer 3

pathological is caused by chronic hypertension and aortic valve stenosis, etc. Physiological is caused by chronic exercise and pregnancy.

Question 4

Myosin HC isoforms

Answer 4

alpha and beta isoforms in the heart. Heterodimers (aa, ab, bb) have different ATPase activity

Question 5

Describe myosin isoform changes with cardiac hypertrophy

Answer 5

In pathological hypertrophy, decrease in ATPase and increased BB Myosin HC. In physiological, there is an increase in ATPase and aa myosin HC

Question 6

The heart has _________ and ___________ plasticity

Answer 6

phenotypic and genotypic

Question 7

Old view of the heart

Answer 7

terminally differentiated, inert structure which does not change its intristic contractile properties when enlarged

Question 8

New view of the heart

Answer 8

Cardiac adaptation is dynamic and involves architectural and structural modifications. In response to stress, quality and quantity are changed. Gene and protein expression change

Question 9

As ATPase activity increases, so does___________

Answer 9

velocity of contraction

Question 10

Which myosin HC has high ATPase activity? Which is slow?

Answer 10

BB has low ATPase activity. AA has high ATPase activity

Question 11

Cellular mechanisms of left ventricular hypertrophy

Answer 11

Increased Ca from L-type Ca channel, reduced SR pump function (via increased PLB to SERCA ratio), impaired myofilament relaxation and increased cytosolic Ca.

Question 12

Describe the phenotypic changes that occur in LVh

Answer 12

increased end diastolic pressure with decreased end diastolic volume

Question 13

Which regulatory proteins are expressed early/acute and which are expressed late/chronic?

Answer 13

Earl/acute: PKA and PKCbeta. Late: PKCepsilon/PKD, CAMK, calcineurin

Question 14

Describe Ca waves in normal vs failing cardiocyte

Answer 14

normal: coordinate wave of Ca. Failing: discordinate wave of Ca

Question 15

SERCA2 treatment

Answer 15

Using a virus containing functional SERCA2 to infect failing cardiac cells improves function

Question 16

How is transcription regulated in cardiac cells?

Answer 16

Calcineurin is a Ca dependent phosphatase which dephosphorylates NFAT, allowing NFAT to move to the nucleus where it functions as a trxn factor

Question 17

What happens to LV function after an acute insult

Answer 17

There is immediate damage from the acute insult, then continuous damage (at a slower rate) occurs over time. This is due to positive feedback mechanisms that amplify disease severity