TIMP-4 inhibits several soluble MMPs (types 1, 2, 3, 7, 8, 9, 12, 13, 19, and 26) and membrane-type MMPs (MT1, MT2, and MT3). It also inhibits a disintegrin and metalloproteinase (ADAM) 28 and ADAM33. It is expressed highly in heart and found dysregulated in human cardiovascular diseases []. Tissue inhibitors of metalloproteinases (TIMPs) are natural inhibitors of matrix metalloproteinases (MMPs) found in most tissues and body fluids. By inhibiting MMPs activities, they participate in tissue remodeling of the extracellular matrix (ECM). The balance between MMPs and TIMPs activities is involved in both normal and pathological events such as wound healing, tissue remodeling, angiogenesis, invasion, tumourigenesis and metastasis []. TIMPs also exhibit functions that appear to be independent of their metalloproteinase inhibitory capacity []. There are four mammalian TIMPs (TIMP-1 to -4), and each TIMP has its own profile of metalloproteinase inhibition.
