Inhibition of MMP-2 Expression with siRNA Increases Baseline Cardiomyocyte Contractility and Protects against Simulated Ischemic Reperfusion Injury

<table>Effect of MMP-2 siRNA transfection on MMP-2 expression in isolated cardiomyocytes. (a) Efficiency of siRNA transfection and MMP-2 protein levels measured by immunocytochemistry. Scale bar, 50 <i>μ</i>m. (b) Measurement of MMP-2 gelatinolytic activity by zymography. (c) MMP-2 protein level. (a) <svg height="11.125" id="M5" style="vertical-align:-0.17555pt" version="1.1" viewbox="0 0 44.400002 11.125" width="44.400002" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink">
<g transform="matrix(.017,-0,0,-.017,.062,10.862)"><path d="M495 86q-46 -47 -87 -72.5t-63 -25.5q-43 0 -16 107l49 210q7 34 8 50.5t-3 21t-13 4.5q-35 0 -109.5 -72.5t-115.5 -140.5q-21 -75 -38 -159q-50 -10 -76 -21l-6 8l84 340q8 35 -4 35q-17 0 -67 -46l-15 26q44 44 85.5 70.5t64.5 26.5q35 0 10 -103l-24 -98h2
q42 56 97 103.5t96 71.5q46 26 74 26q9 0 16 -2.5t14 -11.5t9.5 -24.5t-1 -44t-13.5 -68.5q-30 -117 -47 -200q-4 -19 -3.5 -25t6.5 -6q21 0 70 48z" id="x1D45B"></path></g><g transform="matrix(.017,-0,0,-.017,13.305,10.862)"><path d="M535 323h-483v50h483v-50zM535 138h-483v50h483v-50z" id="x3D"></path></g><g transform="matrix(.017,-0,0,-.017,28.008,10.862)"><path d="M412 140l28 -9q0 -2 -35 -131h-373v23q112 112 161 170q59 70 92 127t33 115q0 63 -31 98t-86 35q-75 0 -137 -93l-22 20l57 81q55 59 135 59q69 0 118.5 -46.5t49.5 -122.5q0 -62 -29.5 -114t-102.5 -130l-141 -149h186q42 0 58.5 10.5t38.5 56.5z" id="x32"></path></g><g transform="matrix(.017,-0,0,-.017,36.168,10.862)"><path d="M153 550l-26 -186q79 31 111 31q90 0 141.5 -51t51.5 -119q0 -93 -89 -166q-85 -69 -173 -71q-32 0 -61.5 11.5t-41.5 23.5q-18 17 -17 34q2 16 22 33q14 9 26 -1q61 -50 124 -50q60 0 93 43.5t33 104.5q0 69 -41.5 110t-121.5 41q-53 0 -102 -20l38 305h286l6 -8
l-26 -65h-233z" id="x35"></path></g>
</svg> cells from 3 different hearts per group; <svg height="11.175" id="M6" style="vertical-align:-0.27588pt" version="1.1" viewbox="0 0 58.612499 11.175" width="58.612499" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink">
<g transform="matrix(.017,-0,0,-.017,.062,10.862)"><path d="M495 86q-46 -47 -87 -72.5t-63 -25.5q-43 0 -16 107l49 210q7 34 8 50.5t-3 21t-13 4.5q-35 0 -109.5 -72.5t-115.5 -140.5q-21 -75 -38 -159q-50 -10 -76 -21l-6 8l84 340q8 35 -4 35q-17 0 -67 -46l-15 26q44 44 85.5 70.5t64.5 26.5q35 0 10 -103l-24 -98h2
q42 56 97 103.5t96 71.5q46 26 74 26q9 0 16 -2.5t14 -11.5t9.5 -24.5t-1 -44t-13.5 -68.5q-30 -117 -47 -200q-4 -19 -3.5 -25t6.5 -6q21 0 70 48z" id="x1D45B"></path></g><g transform="matrix(.017,-0,0,-.017,13.305,10.862)"><path d="M535 323h-483v50h483v-50zM535 138h-483v50h483v-50z" id="x3D"></path></g><g transform="matrix(.017,-0,0,-.017,28.008,10.862)"><path d="M244 635q90 0 143 -72t53 -177q0 -133 -65 -229.5t-171 -139.5q-79 -32 -140 -32l-5 30q109 18 185 91t101 186l-68 -36q-29 -16 -60 -16q-79 0 -129 51.5t-50 130.5q0 80 57 146.5t149 66.5zM228 602q-52 0 -78 -45.5t-26 -98.5q0 -69 36.5 -115.5t97.5 -46.5
q53 0 90 28q4 31 4 66q0 51 -9.5 95.5t-39 80.5t-75.5 36z" id="x39"></path></g><g transform="matrix(.017,-0,0,-.017,36.168,10.862)"><path d="M300 253l-14 -55h-229l14 55h229z" id="x2D"></path></g><g transform="matrix(.017,-0,0,-.017,42.219,10.862)"><path d="M384 0h-275v27q67 5 81.5 18.5t14.5 68.5v385q0 38 -7.5 47.5t-40.5 10.5l-48 2v24q85 15 178 52v-521q0 -55 14.5 -68.5t82.5 -18.5v-27z" id="x31"></path></g><g transform="matrix(.017,-0,0,-.017,50.379,10.862)"><path d="M241 635q53 0 94 -28.5t63.5 -76t33.5 -102.5t11 -116q0 -58 -11 -112.5t-34 -103.5t-63.5 -78.5t-94.5 -29.5t-95 28t-64.5 75t-34.5 102.5t-11 118.5q0 58 11.5 112.5t34.5 103t64.5 78t95.5 29.5zM238 602q-32 0 -55.5 -25t-35.5 -68t-17.5 -91t-5.5 -105
q0 -76 10 -138.5t37 -107.5t69 -45q32 0 55.5 25t35.5 68.5t17.5 91.5t5.5 105t-5.5 105.5t-18 92t-36 68t-56.5 24.5z" id="x30"></path></g>
</svg> heart isolates per group for MMP-2 activity (b), in (c) <svg height="11.075" id="M7" style="vertical-align:-0.10033pt" version="1.1" viewbox="0 0 36.237499 11.075" width="36.237499" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink">
<g transform="matrix(.017,-0,0,-.017,.062,10.8)"><path d="M495 86q-46 -47 -87 -72.5t-63 -25.5q-43 0 -16 107l49 210q7 34 8 50.5t-3 21t-13 4.5q-35 0 -109.5 -72.5t-115.5 -140.5q-21 -75 -38 -159q-50 -10 -76 -21l-6 8l84 340q8 35 -4 35q-17 0 -67 -46l-15 26q44 44 85.5 70.5t64.5 26.5q35 0 10 -103l-24 -98h2
q42 56 97 103.5t96 71.5q46 26 74 26q9 0 16 -2.5t14 -11.5t9.5 -24.5t-1 -44t-13.5 -68.5q-30 -117 -47 -200q-4 -19 -3.5 -25t6.5 -6q21 0 70 48z" id="x1D45B"></path></g><g transform="matrix(.017,-0,0,-.017,13.305,10.8)"><path d="M535 323h-483v50h483v-50zM535 138h-483v50h483v-50z" id="x3D"></path></g><g transform="matrix(.017,-0,0,-.017,28.008,10.8)"><path d="M456 178h-96v-72q0 -51 12.5 -62.5t72.5 -16.5v-27h-256v27q65 5 78 17t13 62v72h-260v28q182 271 300 426h40v-407h96v-47zM280 225v295h-2q-107 -148 -196 -295h198z" id="x34"></path></g>
</svg> heart isolates per group, <svg height="17.825001" id="M8" style="vertical-align:-3.13504pt" version="1.1" viewbox="0 0 66.324997 17.825001" width="66.324997" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink">
<g transform="matrix(.012,-0,0,-.012,.062,5.525)"><path d="M471 153q-22 -15 -61 -13q-25 31 -45.5 49.5t-56.5 41.5q4 -71 28 -134q-17 -33 -42 -46q-24 12 -42 46q24 63 28 134q-36 -23 -56.5 -41.5t-45.5 -49.5q-36 -2 -61 13q0 28 19 59q65 10 130 43q-65 33 -130 43q-19 31 -19 59q22 15 61 13q25 -31 45.5 -49.5t56.5 -41.5
q-4 71 -28 134q17 33 42 46q24 -12 42 -46q-24 -63 -28 -134q36 23 56.5 41.5t45.5 49.5q36 2 61 -13q0 -28 -19 -59q-65 -10 -130 -43q65 -33 130 -43q19 -31 19 -59z" id="x2217"></path></g>
<g transform="matrix(.017,-0,0,-.017,7.675,14.875)"><path d="M619 482q0 -69 -40.5 -119t-96 -72.5t-118.5 -26.5h-44l-70 20l-31 -151q-14 -67 0.5 -83t89.5 -22l-5 -28h-287l8 28q65 7 81.5 22t29.5 83l79 398q12 56 0.5 70.5t-78.5 20.5l7 28h255q108 0 164 -43t56 -125zM524 478q0 141 -146 141q-25 0 -47 -8q-16 -6 -20.5 -13.5
t-10.5 -39.5l-43 -241q37 -13 83 -13q67 0 125.5 45t58.5 129z" id="x1D443"></path></g><g transform="matrix(.017,-0,0,-.017,23.2,13.688)"><path d="M512 -3l-437 233v51l437 233v-58l-378 -200v-2l378 -199v-58z" id="x3C"></path></g><g transform="matrix(.017,-0,0,-.017,37.887,13.688)"><path d="M241 635q53 0 94 -28.5t63.5 -76t33.5 -102.5t11 -116q0 -58 -11 -112.5t-34 -103.5t-63.5 -78.5t-94.5 -29.5t-95 28t-64.5 75t-34.5 102.5t-11 118.5q0 58 11.5 112.5t34.5 103t64.5 78t95.5 29.5zM238 602q-32 0 -55.5 -25t-35.5 -68t-17.5 -91t-5.5 -105
q0 -76 10 -138.5t37 -107.5t69 -45q32 0 55.5 25t35.5 68.5t17.5 91.5t5.5 105t-5.5 105.5t-18 92t-36 68t-56.5 24.5z" id="x30"></path></g><g transform="matrix(.017,-0,0,-.017,46.046,13.688)"><path d="M113 -12q-24 0 -39.5 16t-15.5 42q0 24 16 40.5t40 16.5t40 -16.5t16 -40.5q0 -26 -16 -42t-41 -16z" id="x2E"></path></g><g transform="matrix(.017,-0,0,-.017,49.922,13.688)"><path d="M241 635q53 0 94 -28.5t63.5 -76t33.5 -102.5t11 -116q0 -58 -11 -112.5t-34 -103.5t-63.5 -78.5t-94.5 -29.5t-95 28t-64.5 75t-34.5 102.5t-11 118.5q0 58 11.5 112.5t34.5 103t64.5 78t95.5 29.5zM238 602q-32 0 -55.5 -25t-35.5 -68t-17.5 -91t-5.5 -105
q0 -76 10 -138.5t37 -107.5t69 -45q32 0 55.5 25t35.5 68.5t17.5 91.5t5.5 105t-5.5 105.5t-18 92t-36 68t-56.5 24.5z" id="x30"></path></g><g transform="matrix(.017,-0,0,-.017,58.081,13.688)"><path d="M153 550l-26 -186q79 31 111 31q90 0 141.5 -51t51.5 -119q0 -93 -89 -166q-85 -69 -173 -71q-32 0 -61.5 11.5t-41.5 23.5q-18 17 -17 34q2 16 22 33q14 9 26 -1q61 -50 124 -50q60 0 93 43.5t33 104.5q0 69 -41.5 110t-121.5 41q-53 0 -102 -20l38 305h286l6 -8
l-26 -65h-233z" id="x35"></path></g>
</svg> versus aerobic control.</table>

BioMed Research International

fig3

Figure 3

Figure 3: Inhibition of MMP-2 Expression with siRNA Increases Baseline Cardiomyocyte Contractility and Protects against Simulated Ischemic Reperfusion Injury 

Figure 3 | Inhibition of MMP-2 Expression with siRNA Increases Baseline Cardiomyocyte Contractility and Protects against Simulated Ischemic Reperfusion Injury 