Intraluminal Pressure Is Essential for the Maintenance of Smooth Muscle Caldesmon and Filamin Content in Aortic Organ Culture

From Institut National de la Santé et de la Recherche Médicale, Unité 141, Hôpital Lariboisière, Paris, France (N.B., S.L., R.M., A.T.); and the Laboratory of Molecular Endocrinology, Cardiology Research Center of the Russian Academy of Medical Sciences, Moscow, Russia (K.G.B., V.P.S.).

Correspondence to Alain Tedgui, INSERM U141, Hôpital Lariboisière, 41 Blvd de la Chapelle, 75475 Paris, France. E-mail tedgui{at}infobiogen.fr

Abstract—Different forms of mechanical stimulation are among the physiological factors constantly acting on the vessel wall. We previously demonstrated that subjecting vascular smooth muscle cells (VSMCs) in culture to cyclic stretch increased the expression of high-molecular-weight caldesmon, a marker protein of a differentiated, contractile, VSMC phenotype. In the present work the effects of mechanical factors, in the form of circumferential stress and shear stress, on the characteristics of SM contractile phenotype were studied in an organ culture of rabbit aorta. Application of an intralumininal pressure of 80 mm Hg to aortic segments cultured in Dulbecco's modified Eagle's medium containing 20% fetal calf serum for 3 days prevented the decrease in high-molecular-weight caldesmon content (70±4% of initial level in nonpressurized vessel, 116±17% at 80 mm Hg) and filamin content (80±5% in nonpressurized vessel, 100±2% at 80 mm Hg). SM myosin and low-molecular-weight caldesmon contents showed no dependence on vessel pressurization. Neither endothelial denudation nor alteration of intraluminal flow rates affected marker protein content in 3-day vessel culture, thus excluding the possibility of any shear or endothelial effects. Maintenance of high high-molecular-weight caldesmon and filamin levels in the organ cultures of pressurized and stretched vessels demonstrates the positive role of mechanical factors in the control of the VSMC differentiated phenotype.

Key Words: stretch • aorta • marker protein • caldesmon • filamin

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