Connective Tissue Growth Factor could reduce infarct size

Connective Tissue Growth Factor and its cardioprotective capacity is the main focus of Ole Jørgen Kaasbøll‘s PhD thesis.


MAIN RESULTS:

  1. Post-ischemic administration of recombinant human Connective Tissue Growth Factor reduces infarct size in mice.
  2. Primary cardiac fibroblasts are directly targeted by recombinant Connective Tissue Growth Factor.
  3. Connective tissue growth factor is a preproprotein.

THESIS DEFENCE:

Thesis: Studies of the structure-activity relationships, signaling properties and functions of Connective Tissue Growth Factor
Candidate: Ole Jørgen Kaasbøll
Time: February 25 at 12:15
Place: Oslo University Hospital, Rikshospitalet B, Green Auditorium
Link to university website


SUMMARY:

(1) Recombinant human Connective Tissue Growth Factor (CCN2) has cardioprotective capacity when administered after ischemia in an isolated mouse heart system. Half of the mouse hearts in the study had CCN2 injected during the first 15 minutes of reperfusion post-ischemia. CCN2 resulted in smaller infarct size and better preserved cardiac function following 25 as well as 40 minutes of ischemia.

The effect of recombinant human CCN2 on infarct size and cardiac function disappeared with inhibition of the RISK signalling pathway, indicating a cardioprotective effect of CCN2 via RISK signalling.

(3) Recombinant Connective Tissue Growth Factor could stimulate senescence directly in primary cardiac fibroblasts.

(2) Proteolytic processing is necessary to activate Connective Tissue Growth Factor. The carboxyl-terminal domains III and IV constitute the active, mature form of Connective tissue growth factor, which in other words actually is a matricellular preproprotein controlled by proteolytic activation. Kaasbøll and co-workers found this by producing and purifying several variants of recombinant Connective Tissue Growth Factor and investigating how proteolytic processing related to the protein’s biological activity.


REFERENCES:

(1) Kaasbøll, O. J., Moe, I. T., Ahmed, M. S., Stang, E., Hagelin, E. M. V., & Attramadal, H. (2016). CTGF/CCN2 postconditioning increases tolerance of murine hearts towards ischemia-reperfusion injuryPloS one11(2), e0149000.

(2) Kaasbøll, O. J., Gadicherla, A. K., Wang, J. H., Monsen, V. T., Hagelin, E. M. V., Dong, M. Q., & Attramadal, H. (2018). Connective tissue growth factor (CCN2) is a matricellular preproprotein controlled by proteolytic activationJournal of Biological Chemistry293(46), 17953-17970.