L3. Cardiac hypertrophy in health and disease Flashcards
What are the two main types of cardiac hypertrophy?
Physiological and pathological hypertrophy
What is the primary cause of physiological cardiac hypertrophy?
Exercise training and pregnancy
What triggers pathological cardiac hypertrophy?
Pressure or volume overload, such as hypertension or valve regurgitation
What is ‘athlete’s heart’?
A physiological enlargement of the heart due to consistent exercise training
How does Laplace’s Law relate to cardiac hypertrophy?
It explains how the heart remodels to normalize wall stress based on chamber radius and wall thickness
What type of hypertrophy occurs with volume overload?
Eccentric hypertrophy
What type of hypertrophy is caused by pressure overload?
Concentric hypertrophy
What molecular pathway mediates physiological hypertrophy?
Insulin and IGF-1 pathway
Which signalling molecules are key in pathological hypertrophy?
Angiotensin II and Endothelin I
What is the difference between concentric and eccentric hypertrophy?
Concentric hypertrophy involves thickened walls with reduced chamber size, while eccentric involves dilation with wall thickening
What happens to cardiac output during exercise?
Cardiac output increases to meet the demands of working muscles
What is the effect of detraining on an athlete’s heart?
Physiological remodelling reverses with detraining
What is the significance of the resting bradycardia in athletes?
It is associated with sinus node remodelling due to training
What percentage of myocardial cell volume is made up by cardiomyocytes?
0.9
What distinguishes physiological from pathological hypertrophy?
Physiological hypertrophy is reversible and improves function, while pathological is irreversible and leads to heart failure
What role does the IGF-1 receptor play in cardiac hypertrophy?
Overexpression induces physiological hypertrophy and protects against pathological remodelling
What are the characteristics of pathological hypertrophy?
Fibrosis, reduced capillary networks, and activation of foetal gene expression
What is the main difference in the capillary network between physiological and pathological hypertrophy?
Physiological hypertrophy maintains capillary density, while pathological does not
What does foetal gene expression indicate in hypertrophy?
It signifies maladaptive remodelling in pathological hypertrophy
How does pregnancy affect cardiac hypertrophy?
It induces reversible physiological hypertrophy with increased left ventricular mass
What role do microRNAs play in hypertrophy?
They regulate gene expression post-transcriptionally, influencing pathological hypertrophy
What did the TAC model reveal about miR-29 in hypertrophy?
Inhibiting miR-29 alleviates pathological hypertrophy and fibrosis
How is pathological hypertrophy initially compensatory?
It preserves cardiac function before transitioning to decompensated failure
What is a hallmark of heart failure with reduced ejection fraction?
Dilation and decreased systolic function
How do trabeculae change during cardiac maturation?
They compact and contribute to coronary vessel formation
What is the prevalence of LV trabeculation in athletes?
18% compared to 7% in controls
How does eccentric hypertrophy reduce wall stress?
By increasing chamber radius and wall thickness
What happens to the heart in long-term detraining?
Reductions in ventricular dimensions and wall thickness
How do endothelial cells contribute to cardiac remodelling?
By maintaining capillary networks to match muscle growth
What did McMullen’s study on IGF-1 receptor overexpression show?
Improved cardiac performance and protection against fibrosis
What is the role of CaMKII in pathological hypertrophy?
It promotes maladaptive cell growth by exporting histone deacetylases
How does the sarcoplasmic reticulum contribute to hypertrophy signalling?
Releases calcium, which activates calcineurin and other pathways
What is the effect of pregnancy on LV wall stress?
Normalised by increased wall thickness during pregnancy
What does angiogenesis ensure in physiological hypertrophy?
Adequate oxygen and nutrient supply to the growing heart muscle
What did experiments with transgenic mice show about Akt1?
Akt1 activation is essential for IGF-1 mediated hypertrophy
What defines maladaptive remodelling in pathological hypertrophy?
Increased fibrosis and inadequate capillary formation
What is fractional shortening a measure of?
The experimental equivalent of ejection fraction in cardiac studies
How does exercise intensity affect hypertrophy type?
Endurance training leads to eccentric, while strength training leads to concentric hypertrophy
What is the relationship between wall stress and oxygen consumption?
Higher wall stress increases myocardial oxygen demand
How does Laplace’s Law predict heart failure progression?
Increased radius and reduced pressure generation exacerbate wall stress
