Assembly of type I collagen: fusion of fibril subunits and the influence of fibril diameter on mechanical properties.

Structural stability of the extracellular matrix is primarily a consequence of fibrillar collagen and the extent of cross-linking. The relationship between collagen self-assembly, consequent fibrillar shape and mechanical properties remains unclear. Our laboratory developed a model system for the preparation of self-assembled type I collagen fibers with fibrillar substructure mimicking the hierarchical structures of tendon. The present study evaluates the effects of pH and temperature during self-assembly on fibrillar structure, and relates the structural effects of these treatments on the uniaxial tensile mechanical properties of self-assembled collagen fibers. Results of the analysis of fibril diameter distributions and mechanical properties of the fibers formed under the different incubation conditions indicate that fibril diameters grow via the lateral fusion of discrete approximately 4 nm subunits, and that fibril diameter correlates positively with the low strain modulus. Fibril diameter did not correlate with either the ultimate tensile strength or the high strain elastic modulus, which suggests that lateral aggregation and consequently fibril diameter influences mechanical properties during small strain mechanical deformation. We hypothesize that self-assembly is mediated by the formation of fibrillar subunits that laterally and linearly fuse resulting in fibrillar growth. Lateral fusion appears important in generating resistance to deformation at low strain, while linear fusion leading to longer fibrils appears important in the ultimate mechanical properties at high strain.

Predictive accuracy of coronary artery calcification and abnormal exercise test for coronary artery disease in asymptomatic men.

To determine the predictive accuracy of fluoroscopically detected coronary artery calcification (CAC) and a positive submaximal exercise test, 129 asymptomatic men were screened; 13 had both coronary artery calcification and positive exercise test (greater than or equal to 1.0 mm ST-segment depression). These 13 men were studied at coronary arteriography. They had a mean age of 44 years (range 41-56 years); none had history or symptoms of heat disease and all had normal resting ECGs at entry. CAC was detected in one artery in 10 men, in two arteries in two men, and in three arteries in one man. Coronary artery disease (CAD) was considered clinically significant if any major coronary branch was narrowed > 50%. Coronary arteriography revealed 12 men with clinically significant CAD (one-vessel CAD in four, two-vessel CAD in five and three-vessel CAD in three men) and one man with minor one-vessel CAD. The predictive accuracy was 100% for minor CAD and 92% for clinically significant CAD. The location of CAC and CAD correlated, but the absence of CAC did not rule out the presence of CAD at coronary arteriography. Furthermore, CAC did not indicate the location of the highest stenotic (most occlusive) lesions seen at arteriography. Follow-up for the 13 patients was 36 months; three patients developed typical angina and one patient developed a transmural myocardial infarction. This study suggests that the predictive accuracy of CAC and a positive exercise test in the middle-aged non-hyperlipidemic asymptomatic male is very high (100% for CAD and 92% for clinically significant CAD) and that CAC and a positive exercise test predict an early appearance of angina or myocardial infarction in previously asymptomatic men.

Correlation of fluoroscopically detected coronary artery calcification with exercise stress testing in asymptomatic men.

Cardiac fluoroscopy followed by a submaximal exercise electrocardiogram was used to evaluate 129 healthy men (average age 49 p 6) for assessment of possible latent ischemic heart disease in an asymptomatic population. Of 108 subjects who completed the exercise protocol, 37 (34%) had at least one fluoroscopically detected calcified coronary artery. Of the 16 subjects with a positive exercise stress test, 13 (81%) had calcification of at least one coronary artery, Thirteen of 37 (35%) with calcification had a positive exercise test. Those with calcification of at least one coronary artery had a ninefold increased risk of a positive exercise stress test (p less than 0.0001). The location of a calcific deposit conferred greater risk of exercise-induced ischemic changes than did multivessel involvement. Forty-seven per cent of men with calcification in the left anterior descending coronary artery had an abnormal exercise electrocardiogram vs. 33% and 16% of persons with left circumflex and right coronary artery calcifications, respectively.