Histopathologic profiles of coronary atherosclerosis by myocardial bridge underlying myocardial infarction.

OBJECTIVE: Anatomic properties of myocardial bridge (MB) are sometimes responsible for myocardial infarction (MI) through the changes in the atherosclerosis distribution in the left ascending coronary artery (LAD). The purpose of this study was to investigate histopathologic profiles of atherosclerotic lesions resulting from the MB presence in the LAD in the MI cases. METHODS: In 150 consecutive autopsied MI hearts either with MBs [MI(+)MB(+); n = 67] or without MBs [MI(+)MB(-); n = 83] and 100 normal hearts with MBs [MI(-)MB(+)], LADs were consecutively cross-sectioned at 5-mm intervals. The most advanced intimal lesion and unstable plaque-related lesion characteristics (UPLCs) in each section were histopathologically evaluated in conjunction with the anatomic properties of the MB, such as its thickness, length, location, and MB muscle volume burden (MMV: the total volume of MB thickness multiplied by MB length). RESULTS: The MB showed a significantly greater thickness (P = 0.0090), length (P = 0.0300), and MMV (P = 0.0019) in MI(+)MB(+) than in MI(-)MB(+). Mean age of acute MI cases was significantly younger (P = 0.0227) in MI(+)MB(+) than in MI(+)MB(-). Frequency of plaque fissure/rupture in the proximal LAD was significantly higher in acute MI cases of MI(+)MB(+) than in MI(+)MB(-). UPLCs tended to be located proximally in MI(+)MB(+) and frequent 2.0 cm or more proximal to the MB entrance in MI(+)MB(+). CONCLUSION: In MI(+)MB(+), UPLCs tend to be located more proximally, and a plaque in the LAD proximal to the MB is prone to rupture, resulting in MI at younger age.

Connective tissue growth factor is a substrate of ADAM28.

ADAM28, a member of the ADAM (a disintegrin and metalloproteinase) gene family, is over-expressed by carcinoma cells and the expression correlates with carcinoma cell proliferation and progression in human lung and breast carcinomas. However, information about substrates of ADAM28 is limited. We screened interacting molecules of ADAM28 in human lung cDNA library by yeast two-hybrid system and identified connective tissue growth factor (CTGF). Binding of CTGF to proADAM28 was demonstrated by yeast two-hybrid assay and protein binding assay. ADAM28 cleaved CTGF in dose- and time-dependent manners at the Ala(181)-Tyr(182) and Asp(191)-Pro(192) bonds in the hinge region of the molecule. ADAM28 selectively digested CTGF in the complex of CTGF and vascular endothelial growth factor(165) (VEGF(165)), releasing biologically active VEGF(165) from the complex. RT-PCR and immunohistochemical analyses demonstrated that ADAM28, CTGF and VEGF are commonly co-expressed in the breast carcinoma tissues. These data provide the first evidence that CTGF is a novel substrate of ADAM28 and suggest that ADAM28 may promote VEGF(165)-induced angiogenesis in the breast carcinomas by the CTGF digestion in the CTGF/VEGF(165) complex.