Abstract 15789: Smooth Muscle Specific Deletion of N-deacetylase-sulfotransferase1 (Ndst1) Results in Altered Arterial Elasticity
Ndst1 is a rate-determining heparan sulfate proteoglycan (HSPG) biosynthetic enzyme that regulates the sulfation pattern of heparan sulfate side chains attached to proteoglycan core proteins. We previously published that a mouse model with smooth muscle specific deletion of Ndst1 (SM22αcre+Ndst1-/-) exhibited the expected significant reduction in HSPG sulfation and an unexpected significant reduction in vessel size. Despite this, SM22αcre+Ndst1-/- exhibited no change in systemic or diastolic blood pressure compared to WT. This led us to hypothesize that these phenotypic changes could have influenced arterial elasticity. This is important, as loss of arterial elasticity is an early predictor of cardiovascular disease such as hypertension and atherosclerosis. To test this, we measured elastic modulus and circumferential compliance in aorta and thoracodorsal arteries (TDA), respectively. Aortas from 2-5 month old male WT and SM22αcre+Ndst1-/- were clamped and stretched longitudinally and circumferentially (i.e., ring tests) using an Instron test machine. SM22αcre+Ndst1-/- exhibited a decreased longitudinal tangent modulus of 0.69 ± 0.12 MPa (n=5) compared to WT with 2.01 ± 0.17 MPa (n=11, P<0.01). However, circumferential moduli values did not differ (n=3, P=0.32). To measure compliance, TDA from WT (n=6) and SM22αcre+Ndst1-/- (n=8) were mounted onto an arterial myograph and perfused with Kreb’s Buffer at a pressure range of 10 to 140 mmHg. SM22αcre+Ndst1-/- TDA exhibited a decreased vessel lumen but maintained compliance similar to WT. At 110 mmHg, compliance was 86.92 ± 21.07 (WT, n=6) and 121.19 ± 26.17 (SM22αcre+Ndst1-/-, n=8) μm2/mmHg (P=0.32). In conclusion, compliance in TDA or circumferential tangent modulus in aorta was unaffected in SM22αcre+Ndst1-/-. In contrast, SM22αcre+Ndst1-/- exhibited increased compliance (decreased modulus) in response to longitudinal stretch. This suggests that loss of HSPG sulfation may affect elastin fiber organization and/or properties given elastin’s predominant role in longitudinal stretch.
- © 2012 by American Heart Association, Inc.