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Valvular Interstitial Cell Calcification Liwen Gu July 5, 2005 Prof C. Simmons.

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Presentation on theme: "Valvular Interstitial Cell Calcification Liwen Gu July 5, 2005 Prof C. Simmons."— Presentation transcript:

1 Valvular Interstitial Cell Calcification Liwen Gu July 5, 2005 Prof C. Simmons

2 Background Endothelial Cells Interstitial Cells (Fig 28-4) deaths caused by valvular diseases in 2002 (US) Aortic sclerosis: thickening of the valve leaftlets calcification Calcification process The American Journal of Cardiology Vol.94; 2004

3 Objectives How calcification occurs in valvular interstitial cells (VIC) Effects of endothelial cell (EC) paracrine factors on interstitial cells - signaling process Short-term/immediate goal: induce calcification in VIC culture

4 1 st Experiment Purpose: to induce calcification in VIC culture by providing an osteogenic supplemented (OS) media Method: - Porcine Aortic Valvular Interstitial Cells (PAVIC) – 14 days -added 10 mmol/L βGP to VIC media Hypothesis: -more nodule formation compared to control -alkaline phosphatase activity -mineralization Ann Thorac Surg 2003; 75:457-66

5 1 st Experiment (cont’d) Results: +OS control (-OS) Explanations: - βGP is not enough -ALP protocol-no positive control

6 2 nd Experiment Method: -3 time points: 0, 14, 21 days -10 mmol/L βGP + 50μg/mL ascorbic acid + 50ng RANKL (J.J. Kaden et al. Journal of Molecular and Cellular Cardiology 36(2004)57-66)

7 Future Experiments VIC aloneVIC + EC 1.VIC + osteogenic supplement (βGP) 2.VIC + OS (βGP + ascorbic acid) 3.Gene expression 4. VIC + EC conditioned media 5.VIC-EC co-culture 6.VIC collagen gel + EC

8 Future Experiments VIC aloneVIC + EC 1.VIC + osteogenic supplement (βGP) 2.VIC + OS (βGP + ascorbic acid) 3.Gene expression 4. VIC + EC conditioned media 5.VIC-EC co-culture 6.VIC collagen gel + EC

9 Future Experiments VIC aloneVIC + EC 1.VIC + osteogenic supplement (βGP) 2.VIC + OS (βGP + ascorbic acid) 3.Gene expression 4. VIC + EC conditioned media 5.VIC-EC co-culture 6.VIC collagen gel + EC

10 Co-Culture Shin et al. “Endothelial Cells Modulate Osteogenesis in Calcifying Vascular Cells”. J Vasc Res 2004;41: Method: Results:

11 Future Experiments VIC aloneVIC + EC 1.VIC + osteogenic supplement (βGP) 2.VIC + OS (βGP + ascorbic acid) 3.Gene expression 4. VIC + EC conditioned media 5.VIC-EC co-culture 6.VIC collagen gel + EC

12 Acknowledgements Prof C. Simmons Simmons Group: Alice Ho Yifei Wang Samir Raza Jan Chen Joel Rebello Davies lab

13 Thank You! Contact:


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