New Treatments for HF

Question 1

3 Keys of HF

Answer 1

1. Loss of cardiomyocytes
2. Abnormal mechanical function of the cell*
3. Fibrosis (myocytes encased in collagen)

• RNA and global protein increased.
  Foetal gene program.

Question 2

4 themes of Novel Treatment

Answer 2

1. Exogenous SC/progenitor cells
2. Endogenous SC/progenitor cells
3. Stimulate proliferation
4. Block cell death (death/survival signalling)

Question 3

MiRNA

Answer 3

• Inducing proliferation of existing CMs
• Bind to mRNA (one may target many many)
• Either cause cleavage or block translation of the mRNA
• Many targets in HF relating to CMs and fibrosis

Question 4

Nesiritide (ASCEND-HF)

Answer 4

• Nesiritide = Recombinant BNP
• Fluid Homeostasis
• Counter-regulation of RAAS
• cGMP activation, SMC relaxation

Question 5

SERCA gene therapy (CUPID)

Answer 5

• Adeno-vector gene transfer to restore SERCA levels
• Should improve Ca handling, contraction
• Electrical improvements