Mechanical properties of the extracellular matrix alter expression of smooth muscle protein LPP and its partner palladin; relationship to early atherosclerosis and vascular injury.
Lipoma preferred partner (LPP) localizes to focal adhesions/dense bodies, is selectively expressed in smooth muscle cells (SMC) and enhances cell migration. SMCs cultured on denatured collagen or on a rigid substrate, up regulated expression of LPP, its partner palladin, tenascin C (TN-C), phosphorylated focal adhesion kinase (pFAK) and exhibited robust stress fibers. In an endothelial (EC)/SMC hemodynamic flow system, shear stress waveforms mimicking atheroprone flow, applied to the EC layer, significantly decreased expression of SMC LPP and palladin. They were also down regulated with TN-C, in an ApoE murine model of atherosclerosis and with oxidative stress but up regulated in an arterial injury model in response to upstream sequential changes in pFAK, Prx1 and TN-C. In conclusion, expression of LPP and palladin are modulated by a mix of mechanical cues, oxidative stress and substrate composition which translate into their up or down regulation in vessel wall injury and early atherogenesis.
Jin
Li
L
Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22908, USA.
Hastings
Nicole E
NE
Blackman
Brett R
BR
Somlyo
Avril V
AV
D000818:Animals; D001011:Aorta / Q000293:injuries / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D002465:Cell Movement; D003094:Collagen / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000096:biosynthesis* / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D060588:LIM Domain Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D018384:Oxidative Stress; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D033081:Shear Strength; D022502:Stress Fibers / Q000378:metabolism; D019063:Tenascin / Q000378:metabolism
D001057:Apolipoproteins E; D003598:Cytoskeletal Proteins; D060588:LIM Domain Proteins; C103594:LPP protein, human; C412722:PALLD protein, human; D010750:Phosphoproteins; D019063:Tenascin; D003094:Collagen; D051416:Focal Adhesion Protein-Tyrosine Kinases