SLIDE 6 6/21/2013 6
Bone Marrow-Derived Macrophages (BMDMs) – but not SMCs – Responded to Elastin Peptide Treatment by Upregulating Pro-Fibrotic Markers
Ccl12 (SDF-1) Ssp1 (Osteopontin) Tnc (Tenascin-C) Col3a1 (Collagen III) Col1a1 (Collagen I) Thbs1 (Thrombospondin- 1)
Relative Expression to HPRT Relative Expression to HPRT
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Interim Summary:
- Normal conduit PA media (human and bovine,
but not rodent) contains “resident” inflammatory/immunomodulatory leukocytic cells.
- In pulmonary hypertension, increased
accumulation of numbers of these leukocytic cells is observed.
- Elastin peptides induce activation of naïve
macrophages (BMDMs): upregulated mRNA expression of pro-inflammatory and pro-fibrotic markers.
- Is there evidence for central vascular
stiffening in pulmonary hypertension?
- What are the potential cellular
mechanisms contributing to stiffening of the pulmonary artery?
- Should/can anything be done to directly
reduce proximal vascular stiffening in PH?
Pulmonary Circulation: Questions
Low compliance is the leading independent predictor of
mortality
Compliance correlates directly with exercise capacity and
quality of life
Low compliance accounts for up to 50% of RV afterload Low compliance stimulates progression of the disease Pulmonary vascular stiffness is increased 25- to 30-fold etc…
Compliance is Fundamental to PH
1 Campo et al, Am J Respir Crit Care Med, 2009, 2 Mahapatra et al, J Am Soc. Echocardiography, 2006, 3 Mahapatra et al, J Am Col Card, 2006, 4 Gan et al, Chest, 2007, 5 Hunter et al, J Appl Physiol, 2010, 6 Sanz et al, JACC Card. Imag. 2009, 7 Li and Chesler, Pulm. Circ. 2011, 8 Perrot et al, Chest, 2011, 9 Bonderman et al, Chest, 2011, 10 Saouti et al, Am J Respir Crit Care Med, 2010, 11 Milnor et al, Circ Res, 1966, 12 Milnor et al, Circ Res, 1969, 13 Wang and Chesler, Pulm Circ, 2011, 14 Stenmark et al, Circ Res, 2006, 15 Birukov Andiox Redox Sig, 2009 , 16 Li et al, Ann Biomed Eng, 2009 , 17 Stevens et al, JACC, Cardiovascular Imaging, 2012
