Noninvasive targeted imaging of matrix metalloproteinase activation in a murine model of postinfarction remodeling.

Background: Time-dependent activation of matrix metalloproteinases (MMPs) after myocardial infarction (MI) contributes to adverse left ventricular (LV) remodeling; however, noninvasive methods to monitor this process serially are needed.

Methods And Results: MMP-targeted radiotracers were developed that displayed selective binding kinetics to the active MMP catalytic domain. Initial nonimaging studies were performed with a (111)In-labeled MMP-targeted radiotracer ((111)In-RP782) and negative control compound ((111)In-RP788) in control mice (Ctrl) and in mice 1 week after surgically induced MI.

Time-dependent changes in myocardial structure following discrete injury in mice deficient of matrix metalloproteinase-3.

Myocardial scars from radiofrequency (RF) ablation can increase in size in the post-injury period, resulting in remodeling of the extracellular matrix (ECM). The matrix metalloproteinases (MMPs) contribute to adverse myocardial remodeling following injury. However, the role of specific MMP types in RF scar enlargement remains unclear.

Age-dependent changes in myocardial matrix metalloproteinase/tissue inhibitor of metalloproteinase profiles and fibroblast function.

Objective: To evaluate the effects of aging on left ventricular (LV) geometry, collagen levels, matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) abundance, and myocardial fibroblast function.

Methods: Young (3-month-old; n=28), middle-aged (MA; 15-month-old; n=17), and old (23-month-old; n=16) CB6F1 mice of both sexes were used in this study. Echocardiographic parameters were measured; collagen, MMP, and TIMP levels were determined for both the soluble and insoluble protein fractions; and fibroblast function was evaluated.

Effects of deletion of the tissue inhibitor of matrix metalloproteinases-1 gene on the progression of murine thoracic aortic aneurysms.

Objective: The cause of thoracic aortic aneurysms (TAAs) is poorly understood. Previous work has suggested an association between development of aortic aneurysms and matrix metalloproteinase (MMP) activity. We hypothesized that removal of the primary endogenous aortic MMP inhibitor (TIMP) through TIMP-1 gene deletion will increase TAA progression.

Myocardial remodeling after discrete radiofrequency injury: effects of tissue inhibitor of matrix metalloproteinase-1 gene deletion.

Discrete myocardial lesions created through the delivery of radiofrequency (RF) energy can expand; however, the mechanisms have not been established. Matrix metalloproteinases (MMPs) play an important role in myocardial remodeling, and MMP activity can be regulated by the tissue inhibitors of the metalloproteinases (TIMPs). This study examined the role of TIMP-1 in postinjury myocardial remodeling.

A murine model of thoracic aortic aneurysms.

Background: The mechanisms of thoracic aortic aneurysm (TAA) formation are poorly understood, mainly due to the lack of a useful and reproducible model. Accordingly, the goal of this study was to test the hypothesis that abluminal calcium chloride (CaCl(2)) application could create TAAs in the mouse.

Materials And Methods: Adult 129/SvE mice (n = 8) were anesthetized and their thoracic aortas exposed via left thoracotomy.