Matrix metalloproteinases: new routes to the use of MT1-MMP as a therapeutic target in angiogenesis-related disease.

Angiogenesis, the formation of new vessels from pre-existing capillaries, is a fundamental physiological process which is also critical for the development of several pathological conditions; thus a diminished angiogenic response is related to ischemic disorders, whereas increased angiogenesis is associated with tumorigenesis and chronic inflammatory diseases. New ways of modulating angiogenesis therefore have potential in the treatment of these diseases. During angiogenesis, normally quiescent endothelial cells (ECs) become migratory and invade the surrounding tissue. To do this, they require a specific enzyme machinery to degrade the tissue barriers presented by the basement membranes and the interstitial matrix. This function is supplied by matrix metalloproteinase (MMP) proteins, a large family of enzymes responsible for degrading a variety of extracellular matrix (ECM) components and for modulating the bioactivity of transmembrane receptors and soluble factors. In this review we examine the participation of MMPs--in particular membrane type 1-matrix metalloproteinase (MT1-MMP)--in the different steps of angiogenesis, and discuss the mechanisms of regulation of MT1-MMP in ECs. Finally, we explore the potential use of MMP inhibitors (MMPI) in the treatment of angiogenesis-related disease, with especial emphasis on novel approaches to the inhibition of MT1-MMP activity in ECs.

A randomized trial of walking versus physical methods for chronic pain management.

We conducted a pilot study to evaluate a practical exercise program for elderly people with chronic musculo-skeletal pain. Thirty-three subjects (mean age, 73 years; 69% back pain; 24% knee pain; 9% hip pain) were randomly assigned to one of three groups. Group 1 received 6-week supervised program of walking. Group 2 received a pain education program that included instruction and demonstration of use of heat, cold, massage, relaxation and distraction. Group 3 received usual care. Outcomes including pain, self-reported health and functional status, and performance-based measures of functional status were evaluated at baseline, at two weeks and at eight weeks (end of study). Attendance was 100% for the education sessions and 93% for walking sessions. No injuries were sustained. Both intervention groups demonstrated significant improvements in pain (p < 0.05) and performance-based measures of functional status (p < 0.05), while the control group had no changes. These data suggest that patient education and fitness walking can improve overall pain management and related functional limitations among elderly people with chronic musculo-skeletal pain.