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| 2. |
- Jormsjo, S, et al.
(författare)
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Allele-specific regulation of matrix metalloproteinase-7 promoter activity is associated with coronary artery luminal dimensions among hypercholesterolemic patients
- 2001
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Ingår i: Arteriosclerosis, thrombosis, and vascular biology. - : Ovid Technologies (Wolters Kluwer Health). - 1524-4636 .- 1079-5642. ; 21:11, s. 1834-1839
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Tidskriftsartikel (refereegranskat)abstract
- An enhanced expression of matrix metalloproteinase (MMP)-7 has previously been demonstrated in atherosclerotic and aneurysmal tissue. Because perturbed regulation of MMP-7 may influence the development of these diseases, we searched the MMP-7 promoter for functional polymorphisms. An A to G substitution at position −181 (−181 A/G) and a C to T substitution at position −153 (−153 C/T) with frequencies of 0.50 and 0.10, respectively, were identified. Allele-specific associations were studied in 350 patients undergoing percutaneous transluminal coronary angioplasty. Hypercholesterolemic patients carrying the −181G allele or the −153T allele had smaller reference luminal diameters before percutaneous transluminal coronary angioplasty. Reverse transcription–polymerase chain reaction demonstrated that expression of MMP-7 was confined to differentiated U937 cells. Northern blot analysis could not detect an effect of native or oxidatively modified low density lipoprotein on MMP-7 expression. Thus, the limitation of allele-specific effects on vessel wall remodeling to hypercholesterolemic patients may be secondary to lipid-mediated accumulation of MMP-7–expressing monocyte-derived macrophages within the vessel wall. Both polymorphisms influenced the binding of nuclear proteins. Furthermore, in transient transfection studies, the combination of the 2 rare alleles conferred an increased promoter activity. In conclusion, the present study identified and characterized 2 common polymorphisms in the promoter region of the MMP-7 gene that are functional in vitro and seem to influence coronary arterial dimensions in hypercholesterolemic patients with manifest coronary artery disease.
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| 3. |
- Schwartz, GG, et al.
(författare)
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Atorvastatin for acute coronary syndromes
- 2001
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Ingår i: Journal of the American Medical Association (JAMA). - 0098-7484 .- 1538-3598. ; 286:5
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Annan publikation (övrigt vetenskapligt/konstnärligt)
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| 4. |
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| 5. |
- Waters, DD, et al.
(författare)
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Effects of atorvastatin on stroke in patients with unstable angina or non-Q-wave myocardial infarction : A myocardial ischemia reduction with aggressive cholesterol lowering (MIRACL) substudy
- 2002
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 106:13, s. 1690-1695
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Tidskriftsartikel (refereegranskat)abstract
- Background - This report describes the effect of intensive cholesterol lowering with atorvastatin on the incidence of nonfatal stroke, a secondary end point, in a randomized, placebo-controlled trial of patients with unstable angina or non-Q-wave myocardial infarction. The primary end point, a composite of death, nonfatal myocardial infarction, resuscitated cardiac arrest, or recurrent symptomatic myocardial ischemia with objective evidence requiring emergency rehospitalization, was reduced from 17.4% in the placebo group to 14.8% in the atorvastatin group over the 16 weeks of the trial (P=0.048). Methods and Results - Strokes were adjudicated by a blinded end-point committee using standard clinical and imaging criteria. The outcomes of nonfatal stroke and fatal plus nonfatal stroke were analyzed by time to first occurrence during the 16-week trial. Of 38 events (in 36 patients) adjudicated as fatal or nonfatal strokes, 3 were classified as hemorrhagic, one as embolic, and 29 as thrombotic or embolic, 5 could not be categorized. Nonfatal stroke occurred in 9 patients in the atorvastatin group and 22 in the placebo group (relative risk, 0.40, 95% confidence intervals, 0.19 to 0.88, P=0.02). Fatal or nonfatal stroke occurred in 12 atorvastatin patients and 24 placebo patients (relative risk, 0.49, 95% confidence intervals, 0.24 to 0.98, P=0.04). All 3 hemorrhagic strokes occurred in the placebo group. Conclusion - Intensive cholesterol lowering with atorvastatin over 16 weeks in patients with acute coronary syndromes reduced the overall stroke rate by half and did not cause hemorrhagic stroke. These findings need to be confirmed in future trials.
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