Disease relevance of Timp4_mapped

• These findings demonstrate that TIMP-4 can inhibit SMCs migration and induce apoptosis in vitro and in vivo, which may generate new targets for prevention and treatment of vascular diseases [1].
• There was a negative correlation between the recovery of cardiac mechanical function and the release of TIMP-4 during reperfusion in hearts subjected to different durations of ischemia [2].
• CONCLUSIONS: Loss of TIMP-4 from the cardiac myocyte leads to an increase in net myocardial MMP activity that contributes to acute myocardial stunning injury [2].
• Aneurysm formation was associated with an enhanced elastolysis, increased expression of MMP-2 and MMP-3, downregulation of TIMP-4, and with FasL- and caspase-3-mediated apoptosis [3].

High impact information on Timp4_mapped

• We have investigated the time course of expression and localization of TIMP-4 in rat carotid arteries 6 hours, 24 hours, 3 days, 7 days, and 14 days after balloon injury by in situ hybridization, immunohistochemistry, and Western blot analysis [4].
• TIMP-4 protein was present in the adventitia of injured carotid arteries from 24 hours after injury [4].
• We then studied the effect of TIMP-4 protein on the migration of smooth muscle cells through a matrix-coated membrane in vitro and demonstrated a 53% reduction in invasion of rat vascular smooth muscle cells [4].
• To localize MMP-2 and TIMP-4 in situ, immuno-labeling was performed [5].
• TIMP-1 and TIMP-2 mRNA and protein levels increased, and TIMP-4 protein levels decreased in SHHFs vs. controls [6].

Biological context of Timp4_mapped

• TIMP-4 mRNA was also observed in the thecal layer at proestrus, but the punctate pattern within CL and stroma was absent [7].
• At metestrus, TIMP-4 mRNA was present in certain CL from the current and previous cycles and continued to exhibit a punctate pattern of expression in the stroma [7].
• By diestrus, TIMP-4 mRNA was detected in the thecal layer surrounding follicles, and a relatively high level of expression was observed in a punctate pattern within new and previous CL and in the stroma [7].
• TIMP-4 mRNA on the day of estrus was expressed in a punctate pattern in stroma and in corpora lutea (CL) from previous cycles but not in newly formed CL or follicles [7].
• These data and the temporal relationship between the upregulation of TIMP-4, its accumulation, and the onset of collagen deposition suggest an important role for TIMP-4 in the proteolytic balance of the vasculature controlling both smooth muscle migration and collagen accumulation in the injured arterial wall [4].

Anatomical context of Timp4_mapped

• At 7 and 14 days after injury, widespread immunostaining for TIMP-4 was observed throughout the neointima, media, and adventitia of injured arteries [4].
• Moreover, TIMP-4 was present only in thin myofilaments prepared from aerobically perfused hearts but not in ischemic-reperfused hearts [2].
• Immunogold electron microscopy revealed a close association of TIMP-4 with the sarcomeres in aerobically perfused hearts [2].

Associations of Timp4_mapped with chemical compounds

• Ramipril reduced MMP-2 expression (active form), collagen type I mRNA expression and content and increased TIMP-4 levels associated with decreased left ventricular end diastolic pressure (LVEDP), mortality rate and increased LV pressure (LVP) [8].
• Co-incubation of homocysteine and inhibitors of MMP, tissue inhibitor of metalloproteinase-4 (TIMP-4), and caspase, YVAD-CHO, improved vascular function [9].

Other interactions of Timp4_mapped

• During reperfusion after ischemia, there was a rapid, enhanced release of TIMP-4, the most abundant TIMP in the heart, into the coronary effluent, as shown both by reverse zymography and Western blot [2].

Analytical, diagnostic and therapeutic context of Timp4_mapped

• The levels of TIMP-4 were measured by western blot analysis [5].
• The localization of TIMP-4 mRNA was determined by in situ hybridization in adult cycling rats [7].
• All parameters improved after TIMP-4 gene therapy [10].

References