We will investigate the coronary arterial vasculature to determine the role of vascular remodeling in coronary vascular pathology. Inward remodeling results in a reduction of maximum vessel lumen diameter and compromises coronary blood flow. Vascular remodeling has been implicated in coronary flow complications associated with atherosclerosis, hypertension, restenosis and the pathologies of coronary bypass surgery. Our hypothesis is that vascular tone is the primary trigger for coronary arterial inward remodeling. Because many circulating factors found in vivo affect vascular tone, and because in vivo vascular hemodynamics are inherently complex, a novel in vitro system will be used that can simplify and separately examine contributing factors. Cannulated, perfused vessel segments cultured in the system maintain intact smooth muscle function and endothelium dependent dilation for up to fourteen days. Among other broader experimental objectives, the specific objective of this study to be undertaken during the course of my sabbatical is to determine the effect of conditions common to coronary artery disease on in vitro coronary vascular remodeling. Additionally, by conducting initial studies on ovarian resistance arteries, I also will undertake these objectives: to determine whether cyclic remodeling of ovarian resistance vessels occurs in vivo; and to optimize techniques for the culturing of ovarian resistance vessels.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
National Research Service Awards for Senior Fellows (F33)
Project #
1F33HL072548-01
Application #
6583442
Study Section
Special Emphasis Panel (ZRG1-F10 (20))
Program Officer
Commarato, Michael
Project Start
2003-01-14
Project End
Budget Start
2003-01-14
Budget End
2004-01-13
Support Year
1
Fiscal Year
2003
Total Cost
$50,808
Indirect Cost
Name
University of Amsterdam
Department
Type
DUNS #
City
Amsterdam
State
Country
Netherlands
Zip Code
Sweeney, Terrence E; Bagher, Pooneh; Bailey, Jocelyn et al. (2007) Intravascular pressure and diameter profile of the utero-ovarian resistance artery network: estrous cycle-dependent modulation of resistance artery tone. Am J Physiol Heart Circ Physiol 293:H2937-44
Koop, Elianne A; Gebbink, Martijn F B G; Sweeney, Terrence E et al. (2005) Impaired flow-induced dilation in mesenteric resistance arteries from receptor protein tyrosine phosphatase-mu-deficient mice. Am J Physiol Heart Circ Physiol 288:H1218-23
Sorop, Oana; Spaan, Jos A E; Sweeney, Terrence E et al. (2003) Effect of steady versus oscillating flow on porcine coronary arterioles: involvement of NO and superoxide anion. Circ Res 92:1344-51