PMID- 18038419 OWN - NLM STAT- MEDLINE DCOM- 20080219 LR - 20071126 IS - 1932-6254 (Print) IS - 1932-6254 (Linking) VI - 1 IP - 4 DP - 2007 Jul-Aug TI - Spatial differences of cellular origins and in vivo hypoxia modify contractile properties of pulmonary artery smooth muscle cells: lessons for arterial tissue engineering. PG - 287-95 AB - Tissue engineering of functional arteries is challenging. Within the pulmonary artery wall, smooth muscle cells (PASMCs) have site-specific developmental and functional phenotypes, reflecting differing contractile roles. The force generated by PASMCs isolated from the inner 25% and outer 50% of the media of intrapulmonary elastic arteries from five normal and eight chronically hypoxic (hypertensive) 14 day-old piglets was quantified in a three-dimensional (3D) collagen construct, using a culture force monitor. Outer medial PASMCs from normal piglets exerted more force (528 +/- 50 dynes) than those of hypoxic piglets (177 +/- 42 dynes; p < 0.01). Force generation by inner medial PASMCs from normal and hypoxic piglets was similar (349 +/- 35 and 239 +/- 60 dynes). In response to agonist (thromboxane) stimulation, all PASMCs from normal and hypoxic piglets contracted, but the increase in force generated by outer and inner hypoxic PASMCs (ranges 13-72 and 14-56 dynes) was less than by normal PASMCs (ranges 27-154 and 34-159 dynes, respectively; p < 0.05 for both). All hypoxic PASMCs were unresponsive to antagonist (sodium nitroprusside) stimulation, all normal PASMCs relaxed (range - 87 to - 494 dynes). Myosin heavy chain expression by both hypoxic PASMC phenotypes was less than normal (p < 0.05 for both), as was the activity of focal adhesion kinase, regulating contraction, in hypoxic inner PASMCs (p < 0.01). Chronic hypoxia resulted in the development of abnormal PASMC phenotypes, which in collagen constructs exhibited a reduction in contractile force and reactivity to agonists. Characterization of the mechanical response of spatially distinct cells and modification of their behaviour by hypoxia is critical for successful tissue engineering of major blood vessels. FAU - Hall, S M AU - Hall SM AD - University College London, Institute of Child Health, 30 Guilford Street, London, UK. s.hall@ich.ucl.ac.uk FAU - Soueid, A AU - Soueid A FAU - Smith, T AU - Smith T FAU - Brown, R A AU - Brown RA FAU - Haworth, S G AU - Haworth SG FAU - Mudera, V AU - Mudera V LA - eng PT - Journal Article PL - England TA - J Tissue Eng Regen Med JT - Journal of tissue engineering and regenerative medicine JID - 101308490 RN - 0 (Contractile Proteins) RN - 0 (Cytoskeletal Proteins) RN - 0 (Vasoconstrictor Agents) SB - IM MH - Animals MH - Cell Hypoxia MH - Cells, Cultured MH - Contractile Proteins/metabolism MH - Cytoskeletal Proteins/metabolism MH - *Muscle Contraction/drug effects MH - Muscle Relaxation/drug effects MH - Myocytes, Smooth Muscle/*cytology/drug effects/metabolism MH - Pulmonary Artery/*cytology/drug effects/metabolism MH - Swine MH - *Tissue Engineering MH - Vasoconstrictor Agents/pharmacology EDAT- 2007/11/27 09:00 MHDA- 2008/02/20 09:00 CRDT- 2007/11/27 09:00 PHST- 2007/11/27 09:00 [pubmed] PHST- 2008/02/20 09:00 [medline] PHST- 2007/11/27 09:00 [entrez] AID - 10.1002/term.39 [doi] PST - ppublish SO - J Tissue Eng Regen Med. 2007 Jul-Aug;1(4):287-95. doi: 10.1002/term.39.