Abnormal extracellular matrix protein transport associated with increased apoptosis of vascular smooth muscle cells in Marfan syndrome and bicuspid aortic valve thoracic aortic aneurysm

Background - Marfan syndrome (MS) is a genetic disorder caused by a mutation in the fibrillin gene FBN1. Bicuspid aortic valve (BAV) is a congenital heart malformation of unknown cause. Both conditions are associated with ascending aortic aneurysm and premature death. This study examined the relationship among the secretion of extracellular matrix proteins fibrillin, fibronectin, tenascin, and vascular smooth muscle cell (VSMC) apoptosis. The role of matrix metalloproteinase (MMP)- 2 in VSMC apoptosis was studied in MS aneurysm. Methods and Results - Aneurysm tissue was obtained from patients undergoing surgery ( MS: 4 M, 1 F, age 27 - 45 years; BAV: 3 M, 2 F, age 28 - 65 years). Normal aorta from subjects with nonaneurysm disease was also collected ( 4 M, 1 F, age 23 - 93 years). MS and BAV aneurysm histology showed areas of cystic medial necrosis (CMN) without inflammatory infiltrate. Immunohistochemical study of cultured MS and BAV VSMC showed intracellular accumulation and reduction of extracellular distribution of fibrillin, fibronectin, and tenascin. Western blot showed no increase in expression of fibrillin, fibronectin, or tenascin in MS or BAV VSMC and increased expression of MMP-2 in MS VSMCs. There was 4-fold increase in loss of cultured VSMC incubated in serum-free medium for 24 hours in both MS ( 27 +/- 8%) and BAV ( 32 +/- 14%) compared with control ( 7 +/- 5%). Conclusions - In MS and BAV there is alteration in both the amount and quality of secreted proteins and an increased degree of VSMC apoptosis. Up-regulation of MMP-2 might play a role in VSMC apoptosis in MS VSMC. The findings suggest the presence of a fundamental cellular abnormality in BAV thoracic aorta, possibly of genetic origin.

Abnormal left ventricular filling with increasing age reflects abnormal myocardial characteristics independent of ischemia or hypertrophy

Abnormal left ventricular (IV) filling may occur with increasing age despite apparently normal IV size and function, and is usually attributed to IV hypertrophy and coronary artery disease. The purpose of this study was to determine whether myocardial abnormalities could be identified in 67 such patients (36 men, mean age 57 +/- 9 years) whose IV hypertrophy and coronary artery disease were excluded by dobutamine echocardiography. All patients underwent gray scale and color tissue Doppler imaging from 3 apical views, which were stored and analyzed off line. Disturbances in structure and function were assessed by averaging the cyclic variation of integrated backscatter, strain rate, and peak systolic strain from each myocardial segment. Calibrated integrated backscatter (corrected for pericardial backscatter intensity) was measured in the septum and posterior wall from the parasternal long-axis view. Abnormal IV filling was present in 36 subjects (54%). Subjects with and without abnormal IV filling had similar IV mass, but differed in age (p <0.01), cyclic variation (p = 0.001), strain rate (p <0.01), and peak systolic strain (p <0.001). Multivariate logistic regression analysis demonstrated that age (p = 0.016) and cyclic variation (p = 0.042) were the most important determinants of abnormal IV filling in these apparently normal subjects. (C) 2003 by Excerpta Medica, Inc.

Physical activity and sedentary behavior: A population-based study of barriers, enjoyment, and preference

The associations of physical activity and sedentary behavior with barriers, enjoyment, and preferences were examined in a population-based mail survey of 1,332 adults. Respondents reporting high enjoyment and preference for physical activity were more likely to report high levels of activity. Those reporting cost, the weather, and personal barriers to physical activity were less likely to be physically active. Preference for sedentary behavior was associated with the decreased likelihood of being physically active, and the weather as a barrier to physical activity was associated with the increased likelihood of sedentary behavior. These constructs can be used to examine individual and environmental influences on physical activity and sedentary behavior in specific populations and could inform the development of targeted interventions.

Injury related risk behavior - a study of Australian skydivers

Risk taking behaviour has been identified as an important host-related determinant of injury in young adults. The aim of this study is to clarify the relationship between the two key elements of risk taking behaviour - ie, risk assessment and risk acceptance - in participants of a high risk sporting activity. Skydivers registered with the Australian Parachute Federation were sampled at several jump meetings held at three 'drop-zones' in North Eastern Australia. A cross sectional survey of 215 skydivers ascertained each subject's risk assessment of each of nine hypothetical sky diving scenes and whether or not they would jump in the described conditions. Variables which independently predicted an individual's risk assessment were age group (p < 0.05), gender (p < 0.05) and scene details (p < 0.001). Risk assessment was found to be a statistically significant predictor of the decision to jump, with a 22% decrease in the odds of jumping with every unit increase in risk assessment (OR = 0.78: 95% Cl; 0.76, 0.80). Gender was also found to be a statistically significant predictor of the decision to jump, with males being 19% more likely to jump than females, after controlling for age, experience, currency and risk assessment (OR = 1.19: 95% CI; 1.04, 1.38). The importance of these results is that, by quantifying the relationship between two key elements of risk taking behaviour and several important host factor determinants, they facilitate more informed discussion about the possible role of risk taking behaviour in the causation of injury.