Matrix metalloproteinases (MMPs) 9 and 2 are increased in human abdominal aortic aneurysm (AAA) tissue, but their precise role and potential interaction remain unclear. Experimental induction of aortic aneurysms in mice genetically deficient in these peptidases could provide new insight into AAA pathogenesis. Mice deficient in the expression of MMP-9 (MMP-9KO) or MMP-2 (MMP-2KO) and their corresponding wild-type background mice (WT) underwent AAA induction by abluminal application of calcium chloride (CaCl 2 ). No aneurysm formation was observed at 10 weeks after treatment in either the MMP-9KO or the MMP-2KO mice, whereas the corresponding WT mice showed an average 74% and 52% increase in aortic diameter, respectively. Reinfusion of competent macrophages from the corresponding WT strains into knockout mice resulted in reconstitution of AAA in MMP-9KO but not MMP-2KO mice. These findings suggest that macrophage-derived MMP-9 and mesenchymal cell MMP-2 are both required and work in concert to produce AAA.

Matrix metalloproteinases (MMPs) 9 and 2 are increased in human abdominal aortic aneurysm (AAA) tissue, but their precise role and potential interaction remain unclear. Experimental induction of aortic aneurysms in mice genetically deficient in these peptidases could provide new insight into AAA pathogenesis. Mice deficient in the expression of MMP-9 (MMP-9KO) or MMP-2 (MMP-2KO) and their corresponding wild-type background mice (WT) underwent AAA induction by abluminal application of calcium chloride (CaCl 2 ). No aneurysm formation was observed at 10 weeks after treatment in either the MMP-9KO or the MMP-2KO mice, whereas the corresponding WT mice showed an average 74% and 52% increase in aortic diameter, respectively. Reinfusion of competent macrophages from the corresponding WT strains into knockout mice resulted in reconstitution of AAA in MMP-9KO but not MMP-2KO mice. These findings suggest that macrophage-derived MMP-9 and mesenchymal cell MMP-2 are both required and work in concert to produce AAA.

The circulating doxycycline levels of the patients are comparable with those achieved in mice. Doxycycline accounts for an inhibition of 33% to 66% of the aortic growth. The findings suggest that standard doxycycline doses could inhibit AAA growth in humans.

Objective Claudication is the most common manifestation of peripheral arterial disease, producing significant ambulatory compromise. The purpose of our study was to evaluate patients with bilateral lower limb claudication and characterize their gait abnormality based on advanced biomechanical analysis using joint torques and powers. Methods Twenty patients with bilateral claudication (ten with isolated aortoiliac disease and ten with combined aortoiliac and femoropopliteal disease) and sixteen matched controls ambulated on a walkway while three dimensional biomechanical data were collected. Patients walked before and after onset of claudication pain. Joint torques and powers at early-, mid-, and late-stance for the hip, knee and ankle joints were calculated for claudicating patients before and after the onset of claudication pain, and were compared to control subjects. Results Claudicating patients exhibited significantly reduced hip and knee power at early-stance (weight acceptance phase) due to decreased torques produced by the hip and knee extensors. In mid-stance (single limb support phase), patients had significantly reduced knee and hip power due to the decreased torques produced by the knee extensors and the hip flexors. In late-stance (propulsion phase), reduced propulsion was noted with significant reduction in ankle plantar flexor torques and power. These differences were present before and after the onset of pain with certain parameters worsening in association with pain. Conclusions The gait of claudication is characterized by failure of specific and identifiable muscle groups needed to perform normal walking (weight acceptance, single limb support and propulsion). Parameters of gait are abnormal with the first steps taken, in the absence of pain, and certain of these parameters worsen after the onset of claudication pain.