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.
KeywordsLPP Palladin Smooth muscle Injury Atherosclerosis
We gratefully acknowledge Dr. Carol Otey (University of North Carolina at Chapel Hill) for palladin antibody, Dr. Brian Wamhoff for injured rat aorta samples, Mr. John Sanders for immunostaining assistance (University of Virginia).
Sources of funding
Supported by NIH grants PO1 HL48807 and PO1 HL 19842 to A.V.S., NIH R01 HL 082836 to B.R.B. N.E.H. is supported by a basic cardiovascular research training grant NIH 5-T32-HL 0084.
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