A G Vouyouka | PubMed Health

PubMed2001

The role of type I collagen in aortic wall strength with a homotrimeric.

PURPOSE: Elastin and collagen (types I and III) are the primary load-bearing elements in aortic tissue. Deficiencies and derangements in elastin and type III collagen have been associated with the development of aneurysmal disease. However, the role of type I collagen is less well defined. The purpose of this study was to define the role of type I collagen in maintaining biomechanical integrity in the thoracic aorta, with a mouse model that produces homotrimeric type I collagen [alpha1(I)]3, rather than the normally present heterotrimeric [alpha1(I)]2 alpha2(I) type I collagen isotype. METHODS: Ascending and descending thoracic aortas from homozygous (oim/oim ), heterozygous (oim /+), and wildtype (+/+) mice were harvested. Circumferential and longitudinal load-extension curves were used as a means of determining maximum breaking strength (Fmax) and incremental elastic modulus (IEM). Histologic analyses and hydroxyproline assays were performed as a means of determining collagen organization and content. RESULTS: Circumferentially, the ascending and descending aortas of oim /oim mice demonstrated significantly reduced Fmax, with an Fmax of only 60% and 23%, respectively, of wildtype mice aortas. Oim/oim descending aortas demonstrated significantly greater compliance (decreased IEM), and the ascending aortas also exhibited a trend toward increased compliance. Reduced breaking strength was also demonstrated with longitudinal extension of the descending aorta. CONCLUSION: The presence of homotrimeric type I collagen isotype (absence of alpha2(I) collagen) significantly weakens the aorta. This study demonstrates the integral role of type I collagen in the biomechanical and functional properties of the aorta and may help to elucidate the role of collagen in the development of aneurysmal aortic disease or dissection.

Analysis of Variance↗

PubMed1998

Ambient pulsatile pressure modulates endothelial cell proliferation.

Many studies over the last decade have indicated that circulatory forces such as shear stress and cyclic strain can influence the endothelial cell (EC) phenotype. However, very little is known about the in vitro effects of pressure on EC. To study this, cultured bovine aortic EC were grown in custom designed pressure chambers with carefully regulated CO2/air environment. EC were exposed to either atmospheric, static (135 mmHg) or pulsatile pressure (160/110 mmHg). A pulsed pressure frequency of 60 cycles/min was maintained by computer-controlled solenoid valves, placed in series with pressure lines. EC proliferation was determined both by cell count after trypsin release on days 1,3 and 5 and by 3H-thymidine incorporation. By day 5, a significant decrease in cell number occurred in both pressure groups, confirmed by the thymidine studies. No changes were observed in cell morphology and cell viability as assessed by LDH activity studies. To investigate the mechanism of this effect, EC conditioned media from the three pressure conditions were transferred to non-exposed, control EC. Significant cell growth inhibition was demonstrated in the control EC group treated with conditioned media from EC cultured under pulsatile pressure conditions. This finding suggests that EC exposed to pulsatile pressure secrete an autocrine factor with growth inhibitory properties. This effect was not mediated by the growth factors TGFbeta and IL-1 as shown by Northern blot analysis and antibody-neutralization studies.

Animals↗