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Allele-specific reg...
Allele-specific regulation of matrix metalloproteinase-7 promoter activity is associated with coronary artery luminal dimensions among hypercholesterolemic patients
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Jormsjo, S (författare)
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Whatling, C (författare)
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Walter, DH (författare)
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Zeiher, AM (författare)
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- Hamsten, A (författare)
- Karolinska Institutet
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- Eriksson, P (författare)
- Karolinska Institutet
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(creator_code:org_t)
- Ovid Technologies (Wolters Kluwer Health), 2001
- 2001
- Engelska.
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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
- Relaterad länk:
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https://www.ahajourn...
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http://kipublication...
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https://doi.org/10.1...
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Abstract
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- 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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