Uniaxial strain upregulates matrix-degrading enzymes produced by human vascular smooth muscle cells

Abstract

Arteries remodel in response to environmental changes. We investigated whether mechanical strain modulates production of matrix metalloproteinase (MMP)-2 and -9 by cultured vascular smooth muscle cells (SMC). MMP-2 and MMP-9 expression were tested using human saphenous vein SMC cultured on silicone membranes at rest or subjected to physiological levels (5%) of stationary or cyclical (1 Hz) uniaxial strain. Compared with control, stationary strain significantly increased MMP-2 mRNA levels at all time points, whereas cyclic strain decreased it after 48 h. Both secreted and cell-associated pro-MMP-2 levels were increased by stationary strain at all times (P < 0.01), whereas cyclic strain decreased secreted levels after 48 h (P < 0.02). MMP-9 mRNA levels and pro-MMP-9 protein were increased after 48 h of stationary stretch (P < 0.01) compared with both no strain and cyclic strain. Our study indicates that vascular SMC show a selective response to different types of strain. We suggest that local increases in stationary mechanical strain resulting from stenting, hypertension, or atherosclerosis may lead to enhanced matrix degradation by SMC.

Role of Matrix Metalloproteinases in Early Hypertensive Vascular Remodeling

“…Human endothelial cells display upregulation of MMP-2, MMP-14, 25 MMP-1, and membrane type 1-MMP 26 when exposed to cyclic stretch, as do mouse (MMP-2) 8 and human vascular smooth muscle cells (MMP-2 and MMP-9). 7 Similar observations were made in stretched saphenous veins. 9 We reported recently that MMP-2 and MMP-9 activity and expression are accentuated in carotid arteries exposed ex vivo to elevated intraluminal pressure.…”

Different Involvement of Extracellular Matrix Components in Small and Large Arteries During Chronic NO Synthase Inhibition

“…16 Some evidence suggests that mechanical stretch and strain upregulate MMP-2 and MMP-9 in VSMCs. 17 The same was observed when vein grafts were mechanically stretched 18 or when transmural pressure was elevated ex vivo in porcine carotid arteries, 19 suggesting that hypertension could trigger MMP activation in small arteries. Our objectives were to determine the modulation of TN-C and TSP abundance and to examine the kinetic of MMP-2 activation during the development of hypertension-induced remodeling of large and small arteries.…”

Myocardial Matrix Remodeling and the Matrix Metalloproteinases: Influence on Cardiac Form and Function

“…Eccentric hypertrophy involves the addition of sarcomeres in series to achieve an increase in myocyte length. While in both forms of LVH, alterations in loading conditions form the central mechanical stimulus, local elaboration of growth factors such as TGF, and neurohormonal factors as such as ANG II and ET can modify the growth response, and have particular relevance to the ECM (2,12,34,35,41,64,132,134,217,249,250,337,373,404,441,486,488,535). Specifically, since TGF, ANG II, and ET have all been demonstrated to induce increased collagen synthesis in vitro, then it follows that amplification in the formation and/or signaling of these bioactive molecules in vivo would lead to increased ECM accumulation with POH.…”

“…In POH, the accumulation of ECM and eventual myocardial fibrosis significantly contributes to LV function. In particular, enhanced synthesis and deposition of myocardial ECM is directly associated with increased LV myocardial stiffness properties, which in turn causes poor filling characteristics during diastole (12,35,159,191,194,312,314,421,488). Indeed, recent clinical evidence suggests that progressive ECM accumulation and diastolic dysfunction are important underlying pathophysiological mechanisms for heart failure in patients with POH (196,544,545).…”