Compare Familial HCM with adaptive or maladaptive hypertrophic responses

Question 1

Familial HCM Cause

Answer 1

Mutations in genes of the sarcomeric proteins

• MYBPC3, MYH7 (Myosin Heavy chain 7)

also

• TnI/T/C
• TTN
• ACTC

Question 2

Maladaptive Hypertrophy

• Neuroendocrine imbalance

Answer 2

Growth Promoting Signals

• Sympathetic activation
• AnII, Aldosterone, ET
• Arginine vasopressin

Overcome

Anti-proliferative Signals

• Natriuretic peptides
• Bradykinin
• Nitric oxide
• Adrenomedullin

Question 3

Maladaptive Hypertrophy

• Epigenetics

Answer 3

Non-mutational changes to the genome

• DNA methylation
• Histone acetylation
• ATP-dependent chromatin remodelling complexes

Question 4

Calmodulin Pathway of Stress-induced HT

Answer 4

• Calmodulin-dependent Kinase (CaMK)

P’s

• PKD

P’s

• HDACs (leave the nucleus)

Releases

• MEF2 (TF drives HT)

Question 5

Phospholipase Cε (PLCε)

Answer 5

1. Deletion in mice protects against stress HT
2. PLCε is part of a complex at nuclear envelope, with regulators and targets
3. Regulates local PKD and Ca release
4. PI4P is the substrate of PLCε (in perinuclear golgi)