Just what normal blood pressures are, at sea level and elsewhere, is a matter concerning which there is the widest diversity of opinion. Goodman 1 states that the systolic readings for normal young adults are from 120 to 130, and the diastolic about 85. Making the usual allowance for posture, digestive action, psychic disturbances, etc., he thinks that a systolic pressure of more than 140 is pathologic. Harlow Brooks 2 mentions 120 as the usual systolic pressure, but finds that persons whose occupations entail mental activities it normally ranges between 140 and 155. Janeway 3 states that in the great majority of young males 100 to 130 mm. will be found, and names the normal diastolic pressure as from 65 to 110. Faught 4 states that 120 may be taken as the normal systolic pressure the male at age 20, and adds 1 mm. for every additional two
Abstract There is an unmet need for treatments to reduce abdominal aortic aneurysm (AAA) progression. Vascular smooth muscle cell (VSMC) apoptosis precipitates AAA formation, whereas VSMC proliferation repairs the vessel wall. We previously demonstrated that over-expression of EC4-Fc (truncated N-cadherin), or deletion of matrix-metalloproteinase-7 (Mmp-7) reduced VSMC apoptosis in mouse atherosclerotic plaques. Additionally, MMP-7 promotes VSMC apoptosis by cleavage of N-cadherin. We investigated their combined effect on AAA formation. Increased apoptosis and proliferation were observed in human AAA (HAAA) sections compared to normal aortae (HA). This coincided with increased MMP-7 activity and reduced N-cadherin protein levels in HAAA sections compared to HA. Using a mouse model of aneurysm formation, we showed that the combination of Mmp-7 deletion and EC4-Fc overexpression significantly increased AAA severity. Medial apoptosis and proliferation were both significantly reduced in these mice compared to control mice. In vitro , MMP-7 inhibition and EC4-Fc administration significantly supressed human aortic VSMC apoptosis (via activation of PI-3 kinase/Akt signalling) and proliferation. In conclusion, combined Mmp-7 deletion and systemic over-expression of EC4-Fc reduced both proliferation and apoptosis. Reduced proliferation-mediated repair over-rides any benefit of reduced apoptosis, increasing aneurysm severity. Future studies should therefore focus on retarding VSMC apoptosis whilst promoting VSMC proliferation.
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