Effect of normolipemic and hyperlipemic serum on biosynthetic response to cyclic stretching of aortic smooth muscle cells.

Abstract

Arterial smooth muscle cells synthesize matrix macromolecules In response to mechanical stimulation. Exposure to serum llpids also stimulates connective tissue fiber accumulation. To assess the effect of serum llplds on the blosynthetic response to tensile stress, we subjected rabbit aortic smooth muscle cells that were cultured on purified elastin membranes to cyclic stretching and relaxation 50 times per minute In the presence of serum-free medium (SFM), normolipemic serum (NLS), or hyperlipemic serum (HLS). Incorporation of 14 C-prollne Into prollne and Into hydroxyprollne was taken as a measure of protein and collagen synthesis. When cells were grown in plastic Petrl dishes, exposure to NLS or HLS Increased both protein and collagen production to the same extent compared to synthesis In SFM (1.7 times for NLS and 1.6 times for HLS; p<0.001 compared to SFM). For cells grown on stationary elastin membranes, NLS and HLS also Increased protein and collagen synthesis compared to SFM. The effect of NLS was 1.35 times that of HLS for protein and 1.43 times greater for collagen (p<0.03). Cyclic stretching In SFM doubled synthesis for both protein (p<0.002) and collagen (p<0.002) compared to stationary controls, but had no effect on synthesis In NLS. In HLS, however, cyclic stretching elevated synthesis to the same level as was found In NLS (p<0.003). We conclude that the relative Inhibition of synthesis on stationary membranes by HLS was not due to a toxic effect, since HLS Increased synthesis both In Petrl dishes and on elastin membranes, and the amplifying effect of cyclic stretching In HLS was similar to that seen In SFM. The Interactive effects of mechanical stimulation and hyperllpemla may help to account for Individual differences In wall and plaque composition during atherogenesls. (Arteriosclerosis 9:446-452, July/August 1989) S mooth muscle cells may modify their macromolecular microenvironment by synthesizing elastin, collagen, and glycosaminoglycans. 1 • 23 Some of these changes have been associated with mechanical stimuli. During early growth, for example, differences in the rate of matrix fiber accumulation between the ascending aorta and the pulmonary trunk correspond closely to the respective rates of increase of mural tensile stress despite the persistent similarity of cell content for the two vessel segments. 4 In adult mammals, the number and microarchitecture of the musculoelastic layers of the media of homologous arteries is related to vessel diameter and curvature 56 and, therefore, to the distribution of tensile stress in the vessel wall. Under conditions of hypertension, the number of transmural layers may not change, but the cross-sectional area of the media increases in propor-

Effect of stretch on growth and collagen synthesis in cultured rat and lamb pulmonary arterial smooth muscle cells

“…However, it is possible that stretch acts as a hypertrophic stimulus through decreasing the rate of protein degradation, which was not investigated in these studies. Our findings are at variance with those reported for cultured systemic vascular smooth muscle cells, as repetitive stretch of serum deprived aortic smooth muscle cells has been reported to increase the rate of total protein and collagen synthesis Grande et al, 1989). However, as noted above, this response appears to be far less robust than that in cardiac or skeletal muscle cells, and published data are lacking regarding other evidence of growth with stretch, such as RNA synthetic rates or expression of growth-related genes.…”

“…2) In the system employed here, cells adhere to a collagen-coated silicone surface, yet cell adhesion to other proteins (Ingber, 19911, or the presence in the media of other substance(s1 (Saenz et al, 1991) may be necessary for transduction of mechanical stimuli. 3) The magnitudes, rates, and durations of stretch employed in this study were similar to those employed in other studies Grande et al, 1989;Leung et al, 1976;, but it is possible that they are inappropriate relative to the situation in vivo. Our finding c-fos to be inconsistently expressed with stretch suggests the possibility that the stretch protocol used for these experiments may have been just at the threshold for eliciting a physiologic response, and that a more powerful stimulus may have resulted in consistent c-fos expression and perhaps a measurable growth response as well.…”

“…Considerable research has shown stress or strain to modulate growth and phenotype in skeletal (Vandenburgh, 1987;Vandenburgh et al, 1989) and cardiac muscle in vitro (Mann et al, 1989;Kormuro et al, 1991;Sadoshima et al, 19921, but data are considerably less extensive regarding systemic vascular smooth muscle. The rate of total protein and collagen synthesis has been reported to increase with stretch in cultured aortic smooth muscle cells Grande et al, 1989), although the growth response is not particularly robust:…”

“…If baseline protein synthesis is increased by inclusion of 5 % serum, stretch does not further augment total protein or collagen production (Grande et al, 1989), and reports differ on the duration of stretch necessary to increase protein synthesis (c8 h vs. >3 days [Grande et al, 1989;Sumpio et al, 19881).…”

Mechanism of Angiotensin II-mediated Regulation of Fibronectin Gene in Rat Vascular Smooth Muscle Cells

“…Vascular remodeling in hypertension may be an adaptive response to increased transmural pressure (6 -9). Mechanical stress seems to play a direct role in vascular remodeling, since mechanical stretch is able to increase protein synthesis by vascular smooth muscle cells (VSMCs) (10). However, neuronal and humoral factors may be critical in hypertension-induced remodeling of vascular wall.…”