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result sql = Upregulation of elastase proteins results in aortic dilatation in mucopolysaccharidosis I mice.
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result sql = Mucopolysaccharidosis I (MPS I), known as Hurler syndrome in the severe form, is a lysosomal storage disease due to alpha-L-iduronidase (IDUA) deficiency. It results in fragmentation of elastin fibers in the aorta and heart valves via mechanisms that are unclear, but may result from the accumulation of the glycosaminoglycans heparan and dermatan sulfate. Elastin fragmentation causes aortic dilatation and valvular insufficiency, which can result in cardiovascular disease. The pathophysiology of aortic disease was evaluated in MPS I mice MPS I : mice have normal elastic fiber structure and aortic compliance at early ages, which suggests that elastin assembly is normal. Elastin fragmentation and aortic dilatation are severe at 6 months, which is temporally associated with marked increases in mRNA and enzyme activity for two elastin-degrading proteins, matrix metalloproteinase-12 (MMP-12) and cathepsin S. Upregulation of these genes likely involves activation of STAT proteins, which may be induced by structural stress to smooth muscle cells from accumulation of glycosaminoglycans in lysosomes. Neonatal intravenous injection of a retroviral vector normalized MMP-12 and cathepsin S mRNA levels and prevented aortic disease. We conclude that aortic dilatation in MPS I mice is likely due to degradation of elastin by MMP-12 and/or cathepsin S. This aspect of disease might be ameliorated by inhibition of the signal transduction pathways that upregulate expression of elastase proteins, or by inhibition of elastase activity. This could result in a treatment for patients with MPS I, and might reduce aortic aneurism formation in other disorders.
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char = t;code = 116
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = m;code = 109
char = u;code = 117
char = c;code = 99
char = o;code = 111
char = p;code = 112
char = o;code = 111
char = l;code = 108
char = y;code = 121
char = s;code = 115
char = a;code = 97
char = c;code = 99
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = d;code = 100
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = I;code = 73
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = e;code = 101
char = .;code = 46
result sql = Upregulation of elastase proteins results in aortic dilatation in mucopolysaccharidosis I mice.
char = u;code = 117
char = c;code = 99
char = o;code = 111
char = p;code = 112
char = o;code = 111
char = l;code = 108
char = y;code = 121
char = s;code = 115
char = a;code = 97
char = c;code = 99
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = d;code = 100
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = I;code = 73
char = ;code = 32
char = (;code = 40
char = M;code = 77
char = P;code = 80
char = S;code = 83
char = ;code = 32
char = I;code = 73
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = k;code = 107
char = n;code = 110
char = o;code = 111
char = w;code = 119
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = H;code = 72
char = u;code = 117
char = r;code = 114
char = l;code = 108
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = s;code = 115
char = y;code = 121
char = n;code = 110
char = d;code = 100
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = l;code = 108
char = y;code = 121
char = s;code = 115
char = o;code = 111
char = s;code = 115
char = o;code = 111
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = u;code = 117
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = a;code = 97
char = l;code = 108
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = -;code = 45
char = L;code = 76
char = -;code = 45
char = i;code = 105
char = d;code = 100
char = u;code = 117
char = r;code = 114
char = o;code = 111
char = n;code = 110
char = i;code = 105
char = d;code = 100
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = (;code = 40
char = I;code = 73
char = D;code = 68
char = U;code = 85
char = A;code = 65
char = );code = 41
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = i;code = 105
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = y;code = 121
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = t;code = 116
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = a;code = 97
char = g;code = 103
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = e;code = 101
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = f;code = 102
char = i;code = 105
char = b;code = 98
char = e;code = 101
char = r;code = 114
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = a;code = 97
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = h;code = 104
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = t;code = 116
char = ;code = 32
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = v;code = 118
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = v;code = 118
char = i;code = 105
char = a;code = 97
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = i;code = 105
char = s;code = 115
char = m;code = 109
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = u;code = 117
char = n;code = 110
char = c;code = 99
char = l;code = 108
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = ,;code = 44
char = ;code = 32
char = b;code = 98
char = u;code = 117
char = t;code = 116
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = y;code = 121
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = c;code = 99
char = u;code = 117
char = m;code = 109
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = g;code = 103
char = l;code = 108
char = y;code = 121
char = c;code = 99
char = o;code = 111
char = s;code = 115
char = a;code = 97
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = o;code = 111
char = g;code = 103
char = l;code = 108
char = y;code = 121
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = h;code = 104
char = e;code = 101
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = f;code = 102
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = .;code = 46
char = ;code = 32
char = E;code = 69
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = a;code = 97
char = g;code = 103
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = v;code = 118
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = s;code = 115
char = u;code = 117
char = f;code = 102
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = i;code = 105
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = y;code = 121
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = i;code = 105
char = c;code = 99
char = h;code = 104
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = r;code = 114
char = d;code = 100
char = i;code = 105
char = o;code = 111
char = v;code = 118
char = a;code = 97
char = s;code = 115
char = c;code = 99
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = o;code = 111
char = p;code = 112
char = h;code = 104
char = y;code = 121
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = l;code = 108
char = o;code = 111
char = g;code = 103
char = y;code = 121
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = a;code = 97
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = e;code = 101
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char = e;code = 101
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char = w;code = 119
char = a;code = 97
char = s;code = 115
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char = e;code = 101
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char = a;code = 97
char = l;code = 108
char = u;code = 117
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = M;code = 77
char = P;code = 80
char = S;code = 83
char = ;code = 32
char = I;code = 73
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = e;code = 101
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = ;code = 32
char = M;code = 77
char = P;code = 80
char = S;code = 83
char = ;code = 32
char = I;code = 73
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = m;code = 109
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char = c;code = 99
char = e;code = 101
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char = h;code = 104
char = a;code = 97
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char = e;code = 101
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char = e;code = 101
char = l;code = 108
char = a;code = 97
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char = i;code = 105
char = c;code = 99
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char = f;code = 102
char = i;code = 105
char = b;code = 98
char = e;code = 101
char = r;code = 114
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char = s;code = 115
char = t;code = 116
char = r;code = 114
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = u;code = 117
char = r;code = 114
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char = i;code = 105
char = c;code = 99
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char = c;code = 99
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char = p;code = 112
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char = c;code = 99
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char = l;code = 108
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char = g;code = 103
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char = ;code = 32
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char = m;code = 109
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char = .;code = 46
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char = E;code = 69
char = l;code = 108
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char = i;code = 105
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char = a;code = 97
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char = i;code = 105
char = c;code = 99
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char = d;code = 100
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char = l;code = 108
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char = a;code = 97
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char = s;code = 115
char = e;code = 101
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char = ;code = 32
char = 6;code = 54
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char = l;code = 108
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char = s;code = 115
char = o;code = 111
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char = m;code = 109
char = a;code = 97
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char = e;code = 101
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
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char = m;code = 109
char = R;code = 82
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
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char = i;code = 105
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char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
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char = o;code = 111
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char = d;code = 100
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char = a;code = 97
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char = i;code = 105
char = c;code = 99
char = ;code = 32
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char = i;code = 105
char = s;code = 115
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
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char = e;code = 101
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char = c;code = 99
char = o;code = 111
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char = c;code = 99
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char = t;code = 116
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char = ;code = 32
char = m;code = 109
char = i;code = 105
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char = i;code = 105
char = k;code = 107
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char = ;code = 32
char = t;code = 116
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char = ;code = 32
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char = d;code = 100
char = a;code = 97
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char = i;code = 105
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char = ;code = 32
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char = a;code = 97
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char = i;code = 105
char = n;code = 110
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char = y;code = 121
char = ;code = 32
char = M;code = 77
char = M;code = 77
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char = -;code = 45
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char = 2;code = 50
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char = n;code = 110
char = d;code = 100
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char = o;code = 111
char = r;code = 114
char = ;code = 32
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char = a;code = 97
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char = h;code = 104
char = e;code = 101
char = p;code = 112
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = S;code = 83
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = g;code = 103
char = h;code = 104
char = t;code = 116
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char = a;code = 97
char = m;code = 109
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char = l;code = 108
char = i;code = 105
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char = a;code = 97
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = g;code = 103
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = w;code = 119
char = a;code = 97
char = y;code = 121
char = s;code = 115
char = ;code = 32
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char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = u;code = 117
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = e;code = 101
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = o;code = 111
char = f;code = 102
char = ;code = 32
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char = s;code = 115
char = t;code = 116
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
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char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = .;code = 46
char = ;code = 32
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char = h;code = 104
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = u;code = 117
char = l;code = 108
char = d;code = 100
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = M;code = 77
char = P;code = 80
char = S;code = 83
char = ;code = 32
char = I;code = 73
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = g;code = 103
char = h;code = 104
char = t;code = 116
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = e;code = 101
char = u;code = 117
char = r;code = 114
char = i;code = 105
char = s;code = 115
char = m;code = 109
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = o;code = 111
char = r;code = 114
char = d;code = 100
char = e;code = 101
char = r;code = 114
char = s;code = 115
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
result sql = Mucopolysaccharidosis I (MPS I), known as Hurler syndrome in the severe form, is a lysosomal storage disease due to alpha-L-iduronidase (IDUA) deficiency. It results in fragmentation of elastin fibers in the aorta and heart valves via mechanisms that are unclear, but may result from the accumulation of the glycosaminoglycans heparan and dermatan sulfate. Elastin fragmentation causes aortic dilatation and valvular insufficiency, which can result in cardiovascular disease. The pathophysiology of aortic disease was evaluated in MPS I mice MPS I : mice have normal elastic fiber structure and aortic compliance at early ages, which suggests that elastin assembly is normal. Elastin fragmentation and aortic dilatation are severe at 6 months, which is temporally associated with marked increases in mRNA and enzyme activity for two elastin-degrading proteins, matrix metalloproteinase-12 (MMP-12) and cathepsin S. Upregulation of these genes likely involves activation of STAT proteins, which may be induced by structural stress to smooth muscle cells from accumulation of glycosaminoglycans in lysosomes. Neonatal intravenous injection of a retroviral vector normalized MMP-12 and cathepsin S mRNA levels and prevented aortic disease. We conclude that aortic dilatation in MPS I mice is likely due to degradation of elastin by MMP-12 and/or cathepsin S. This aspect of disease might be ameliorated by inhibition of the signal transduction pathways that upregulate expression of elastase proteins, or by inhibition of elastase activity. This could result in a treatment for patients with MPS I, and might reduce aortic aneurism formation in other disorders.
Publication: Mol. Genet. Metab. 2008 Jul ;94(3)::298-304. :doi: 10.1016/j.ymgme.2008.03.018.
Publication Date: 2008 Jul
Study Author(s): Ma, Xiucui;Tittiger, Mindy;Knutsen, Russell H;Kovacs, Attila;Schaller, Laura;Mecham, Robert P;Ponder, Katherine P;
Institution: Department of Internal Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Shortcut link to this study:
Publication Date: 2008 Jul
Study Author(s): Ma, Xiucui;Tittiger, Mindy;Knutsen, Russell H;Kovacs, Attila;Schaller, Laura;Mecham, Robert P;Ponder, Katherine P;
Institution: Department of Internal Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Shortcut link to this study:
Mucopolysaccharidosis I (MPS I), known as Hurler syndrome in the severe form, is a lysosomal storage disease due to alpha-L-iduronidase (IDUA) deficiency. It results in fragmentation of elastin fibers in the aorta and heart valves via mechanisms that are unclear, but may result from the accumulation of the glycosaminoglycans heparan and dermatan sulfate. Elastin fragmentation causes aortic dilatation and valvular insufficiency, which can result in cardiovascular disease. The pathophysiology of aortic disease was evaluated in MPS I mice MPS I : mice have normal elastic fiber structure and aortic compliance at early ages, which suggests that elastin assembly is normal. Elastin fragmentation and aortic dilatation are severe at 6 months, which is temporally associated with marked increases in mRNA and enzyme activity for two elastin-degrading proteins, matrix metalloproteinase-12 (MMP-12) and cathepsin S. Upregulation of these genes likely involves activation of STAT proteins, which may be induced by structural stress to smooth muscle cells from accumulation of glycosaminoglycans in lysosomes. Neonatal intravenous injection of a retroviral vector normalized MMP-12 and cathepsin S mRNA levels and prevented aortic disease. We conclude that aortic dilatation in MPS I mice is likely due to degradation of elastin by MMP-12 and/or cathepsin S. This aspect of disease might be ameliorated by inhibition of the signal transduction pathways that upregulate expression of elastase proteins, or by inhibition of elastase activity. This could result in a treatment for patients with MPS I, and might reduce aortic aneurism formation in other disorders.
PMID: 18479957
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The order of these related concepts is determined by a statistical analysis of the scientific literature. Highest-frequency concepts appear first.
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