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  • Title: Coronary ectasia in familial hypercholesterolemia: histopathologic study regarding matrix metalloproteinases.
    Author: Kajinami K, Kasashima S, Oda Y, Koizumi J, Katsuda S, Mabuchi H.
    Journal: Mod Pathol; 1999 Dec; 12(12):1174-80. PubMed ID: 10619272.
    Abstract:
    A 39-year-old male heterozygous familial hypercholesterolemia patient with marked ectasia over the entire coronary artery tree had been treated with several kinds of lipid-lowering single or combined drug therapies using clofibrate, compactin, cholestyramine, probucol, and pravastatin, and LDL-apheresis. During the 19-year follow-up, he suffered myocardial infarction three times and some of the ectatic coronary segments became enlarged, others narrowed, and one of them occluded in spite of the treatment. At the age of 58, he died after a fourth cardiac attack and subsequent cardiogenic shock. The autopsy indicated that his three coronary arteries showed diffuse ectatic changes and the largest lumen diameter of the left anterior descending artery was 25 mm, of the circumflex artery 12 mm, and of the right coronary artery 13 mm. The ectatic artery wall was not thick and the major part of the lumen was occupied by organized thrombi. Microscopic examinations showed that the larger the diameter of the lumen, the more severe the structural damage of the intima and tunica media and the larger the number of infiltrated cells, including lymphocytes, macrophages, and plasma cells. Immunoreactivity against matrix metalloproteinase (MMP)-1, and MMP-2 was observed in smooth muscle cells, macrophages, lymphocytes, and endothelial cells of the vasa vasorum or neovasculature. MMP-9 immunoreactivity was also localized in intimal foamy macrophages and round cells (macrophages and lymphocytes) of the media and adventitia. MMP-1 increased with the lumen diameter of the ectatic arteries. The ratio of immunoreactivity against both MMP-2 and MMP-9 to that against tissue inhibitor of metalloproteinase (TIMP)-2 also increased with the lumen diameter, but it no longer increased when the diameter was over 10 mm. These observations suggest that the MMP-TIMP system appears to play a significant role in the development of coronary ectasia
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