Cardiovascular Health 3.1 (Heart): Sex, steroids , and cardio protection controversies

Question 1

What is the number 1 cause of death?

Answer 1

Heart disease

Question 2

By how long are heart diseases delayed in women vs men?

Answer 2

~10 year delay.

Question 3

Do pre-menopausal women have a higher chance of an ischaemic event?

Answer 3

No, its a lower risk.

Question 4

Women respond to drugs differently. Give an example with viagra.

Answer 4

Used in heart therapy in male models. Clinical trials on women had no effect. Found to be dependent on oestrogen levels. Had no effect on post-menopausal women who have low levels.

Question 5

What are oestrogen levels dependent on?

Answer 5

Testosterone.

Question 6

What does aromatase do?

Answer 6

Catalyses testosterone to oestrogen conversion.

Question 7

What happens to oestradiol and testosterone levels in males?

Answer 7

Testosterone levels decrease

Oestradiol levels remain stable.

Question 8

What happens to oestradiol and testosterone levels in females?

Answer 8

Both decrease.

Question 9

What are the three oestrogen receptors on the heart?

Answer 9

ERa, ERb, and GPER (g protein coupled).

Question 10

What effect does testosterone have on skeletal muscle?

Answer 10

Anabolic effect.

Question 11

Is cardiac hypertrophy in response to pathology greater in males or females? What does this suggest?

Answer 11

Males. Suggests testosterone drives hypertrophy.

Question 12

Does the heart hypertrophy with no pathology?

Answer 12

Yes it does.

Question 13

How can sex steroids influence muscle fibre contractility?

Answer 13

Can change how Ca2+ enters the cell, influencing contractility.

Question 14

Is the extent of myocyte contraction greater or smaller in females vs males?

Answer 14

It is smaller in females vs males.

Question 15

How does oestrogen affect sarcoplasmic Ca2+? Which pathway does it activate? What is a consequence of this?

Answer 15

Downregulates the release of Ca2+ from the sarcolemma. Done by activating the PI3K and AKT pathway. Suppresses cell death.

Question 16

Are men or women more likely to die of a sudden cardiac death?

Answer 16

Men

Question 17

What happens to risk of subsequent heart failure in pre menopausal women?

Answer 17

More likely to have one.

Question 18

What is ischaemia?

Answer 18

Lack of oxygen to supply metabolic demand.

Question 19

What is reperfusion?

Answer 19

Unblocking a thrombosis via thrombolytics.

Question 20

What are the consequences of reperfusion (name 3)?

Answer 20

Can cause an increase in the amount of reactive oxygen species, and can overload cells with Ca2+, causing contractile dysfunction and cells rip apart. Cell death.

Question 21

What is the difference between males and females in response to reperfusion following ischaemia (name 3)?

Answer 21

Females sustain less damage, less necrosis, and lower arrhythmia duration.

Question 22

What happens to a females response to reperfusion id they had a hysterectomy beforehand? What does this suggest?

Answer 22

They lose their cardioprotection. Suggests oestrogen mediates cardioprotection.

Question 23

Is oestrogen made in just the ovaries?

Answer 23

No, made in many structures.

Question 24

Does the heart produce oestrogen, and if so, where? How can it be detected?

Answer 24

Yes, it is secreted to have a local effect.

Aromatase used to detect this. Atria in humans have aromatase.

Question 25

Is oestrogen production by the heart greater in males or females, and does it diminish with age?

Answer 25

Females secrete more, and decreases with age.

Question 26

What other structure near the heart can aromatase be found?

Answer 26

In the nearby pericardial fat.

Question 27

Obese people will have more pericardial fat. What does this suggest about high oestrogen levels?

Answer 27

Excessive levels of oestrogen in the heart may be detrimental.

Question 28

What happens if a male heart overexpresses aromatase to increase oestrogen?

Answer 28

Expected to have greater recovery for reperfusion.

Opposite happens.

Question 29

What is the effect of aromatase knockout in a female heart?

Answer 29

Expected to recover poorly from reperfusion. Opposite happened, and recovered really well.