TY - JOUR T1 - Endothelial cell mechanics are altered in pulmonary arterial hypertension (PAH) JF - European Respiratory Journal JO - Eur Respir J VL - 38 IS - Suppl 55 SP - p3343 AU - Corey Hardin AU - Ramaswamy Krishnan AU - Dhananjay Tambe AU - Sharif Sheik AU - Greeshma Manomohan AU - Jeffrey Fredberg AU - Aaron Waxman Y1 - 2011/09/01 UR - http://erj.ersjournals.com/content/38/Suppl_55/p3343.abstract N2 - Idiopathic pulmonary arterial hypertension (IPAH) and collagen vascular disease associated PAH (APAH) are associated with a significant elevation of inflammasome activation and release of IL-1β and IL-6 in patient plasma [1]. We hypothesized that these biochemical changes will affect intercellular force distribution in the constituent endothelial cells. To test this hypothesis, we applied to cultured Human Lung Microvascular Endothelial Cell (HLMVEC), serum derived from IPAH and APAH patients, and measured subsequent changes in HLMVEC intercellular forces [2]. In comparison to time-matched controls (n=4), HLMVEC monolayers exposed to patient serum (IPAH, n=7, APAH, n=8) were significantly more contractile (average contractile moment per monolayer; control cells = 153.5 + 13.5 pNm, IPAH cells = 222.3 + 9.6 pNm, and APAH cells = 223.8 + 22.8 pNm) and exhibited greater number of intercellular stress hot-spots. Accordingly, we suggest that inflammasome mediated enhancements in endothelial intercellular forces may play an important role in decreased vascular compliance observed in PAH.References:1. Shaik, R.S., Kolliputi, N., Waxman, A.B., Activation of Inflammasome in Pulmonary Arterial Hypertension. American Journal of Respiratory and Critical Care Medicine, 2010(May);181:A4865.2. Tambe, D.T., Hardin, C., Angelini, T.E., Rajendran, K.,Serra-Picamal, X., Zama, M.,Butler, J.P., Weitz, D.A., Fredberg, J.J.,Trepat, X., Collective Cell Guidance by Cooperative Intercellular Forces. Nature Precedings, 2011. doi:10.1038/npre.2010.5405.1.2010. ER -