C7 Sex, sex steroids, and cardioprotection controversise

Question 1

Difference b/w men and women heart attacks

Answer 1

• Onset of heart attack is later in women than men (after menopause)
  
  • Pathology of heart disease differs b/w men and women → however treatment remains the same
    
    • Women stay in hospital longer but require less surgical procedures (i.e. bypass)

Question 2

Sex steroid hormone production with age: MALES

Answer 2

• Testosterone rise during puberty → slow and steady ↓ with age
• Estrogen slight increase at puberty → stays steady
  
  • Produced in prostate

Question 3

Sex steroid hormone production with age: FEMALES

Answer 3

• Estrogen increases around 10 (puberty) → stays high until menopause (~50)
• Testosterone → declines with age

Question 4

What is estrogen production dependent on?

Answer 4

• Estrogen production is dependent on testosterone levels
• Converted via aromatase

Question 5

Sex steroid receptors in the heart

Answer 5

• Estrogen R:
  
  • ERα, β (predominant), GPE.R
• Androgen R

Question 6

Sex steroids influence on heart growth

Answer 6

• Testosterone → anabolic actions on skeletal muscles
  
  • Able to induce hypertrophic response EVEN in ABSENCE of pathological stimuli
    
    • Through MAPK → protein synthesis
  • Pathological hypertrophic higher in males than females

Question 7

Estrogen Modulation of heart contractility

Answer 7

• Less contraction in female myocytes
  
  • Influenced by estrogen → smaller Ca transit
  • Estrogen → Era & GPER → PI3K → Akt → inhibits Myocyte Ca cycling & cell death

Question 8

Difference b/w ischemic pathology of men and women

Answer 8

• Pre-menopausal women have lower risks of ischemic heart disease
  
  • But more likely to have subsequent heart failure
• Men are more likely to die of SCD

Question 9

Treating ischemia

Answer 9

• Through reperfusion
  
  • But may lead to Ca overload → exacerbate cardiac dysfunction

Question 10

What is the Langendorff perfused heart?

Answer 10

• Animal model heart hooked to perfusion system to mimic normal contractility
  
  • Deliver krebs buffer to heart at a set perfusion pressure which maintains heart function
  • Direction of flow is retrograde (blood into aorta → into coronary arteries)
    
    • Mimics normal blood into coronary arteries
• Cut off perfusion system → mimic ischemia → turns back on after 25 mins
  
  • See how well it recovers

Question 11

Enhanced post-ischemic recovery in females

Answer 11

• Females have greater recovery than males
  
  • ↑functional recovery, ↓arrhythmia and necrotic cell death
  • Ovariectomy → females lose estrogen → lose cardioprotection

Question 12

Is estrogen synthesis restricted to only in the ovaries?

Answer 12

• Expression of aromatase in non-gonadal tissues
  
  • Bones → local estrogen production → protects (M) from osteoporosis
  • Brain → impaired aromatase functions implicated in AD

Question 13

Implication of expression of estrogen in fats around the heart

Answer 13

• May have implications of upregul ating these hormones in obese people

Question 14

Changes of aromatase production with age

Answer 14

• Aromatase ↑ with age

Question 15

How is recovery measured?

Answer 15

• Stabilise → ischemia → reperfusion
• Measure recovery via: % recovery of LV developed pressure (indicates function) at the end of reperfusion

Question 16

Estrogen benefiting male heart?

Answer 16

• Overexpress aromatase in mouse model → ↑estrogen, ↓testosterone
  
  • Heart did worse
• Aromatase KO → Heart recovered better
  
  • Challenge dogma that estrogen good and testosterone bad
• Balance of sex steroids may be crucial