This resubmission consists of a chronological sequence of three overlapping aims which test the overall hypothesis that the vasa vasorum play an important role in the initiation of coronary atherogenesis (i.e., prior to cellular invasion and/or proliferation) by virtue of disturbed solute transport via the vasa vasorum This, in turn, is due to the perfusion pressure in their distal vasa vasorum lumens being less than the compression in the arterial wall. Our approach is to quantitatively describe detailed branching geometry and solute transport of the vasa vasorum of coronary arteries, primarily by use of micro-CT-based imaging methods. This will involve analysis of coronary arteries of normal pigs, a porcine (diet-induced) model of hypercholesterolemia and a porcine (renal artery stent) model of arterial hypertension (both being risk factors for atherogenesis).
AIM I is for the initial development and integration of the various techniques we propose to use throughout the proposal and to establish the normal state.
AIM II applies the developments in Aim I to hypercholesterlemic and to hypertensive pigs' coronary artery walls so as to relate the response of the vasa vasorum to these pathological conditions.
AIM III builds on Aim II in that we will combine the hypercholesterolemia and hypertension to see if they are linearly additive in effect, as would be predicted by our hypothesis. The primary objective is to relate the transport capacity of vasa vasorum to the spatial density of coronary artery vasa vasorum and the fluid dynamic implications of both the 3D branching geometry of the vasa vasorum and the spatial distribution of compressive stresses within the coronary artenal wall. The significance of this proposal is that if the hypothesis of this study is supported, it should give insight into several puzzling observations. One is that atherosclerosis does not generally form in veins (which have vasa vasorum) or in small arteries (which have no vasa vasorum). Equally intriguing is the observation that early atherosclerosis does not form in the outer media or adventitia even though vasa vasorum provide a sizable endothelial surface (which presumably also becomes dysfunctional) in the outer media and adventitia. Another observation is that artenes whose adventitia are manipulated and veins, which are subjected to arterial pressure or surgically manipulated, do develop atherosclerosis.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL065342-03
Application #
6638676
Study Section
Diagnostic Radiology Study Section (RNM)
Program Officer
Goldman, Stephen
Project Start
2001-04-01
Project End
2005-03-31
Budget Start
2003-04-01
Budget End
2004-03-31
Support Year
3
Fiscal Year
2003
Total Cost
$350,284
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
Moritz, Regina; Anderson, Jill L; Vercnocke, Andrew J et al. (2013) Changes in CT angiographic opacification of porcine coronary artery wall with patchy altered flow in vasa vasorum. Int J Cardiovasc Imaging 29:1325-33
Moritz, Regina; Eaker, Diane R; Anderson, Jill L et al. (2012) IVUS detection of vasa vasorum blood flow distribution in coronary artery vessel wall. JACC Cardiovasc Imaging 5:935-40
Stolz, Erwin; Yeniguen, Mesut; Kreisel, Melanie et al. (2011) Angioarchitectural changes in subacute cerebral venous thrombosis. A synchrotron-based micro- and nano-CT study. Neuroimage 54:1881-6
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Easter, Renee N; Qilin Chan; Lai, Barry et al. (2010) Vascular metallomics: copper in the vasculature. Vasc Med 15:61-9
Kampschulte, M; Brinkmann, A; Stieger, P et al. (2010) Quantitative CT imaging of the spatio-temporal distribution patterns of vasa vasorum in aortas of apoE-/-/LDL-/- double knockout mice. Atherosclerosis 212:444-50
Moritz, Regina; Eaker, Diane R; Langheinrich, Alexander C et al. (2010) Quantification of vasa vasorum density in multi-slice computed tomographic coronary angiograms: role of computed tomographic image voxel size. J Comput Assist Tomogr 34:273-8
Langheinrich, Alexander C; Sedding, Daniel G; Kampschulte, Marian et al. (2009) 3-Deazaadenosine inhibits vasa vasorum neovascularization in aortas of ApoE(-/-)/LDL(-/-) double knockout mice. Atherosclerosis 202:103-10
Gössl, M; Versari, D; Lerman, L O et al. (2009) Low vasa vasorum densities correlate with inflammation and subintimal thickening: potential role in location--determination of atherogenesis. Atherosclerosis 206:362-8
Langheinrich, Alexander C; Kampschulte, Marian; Crössmann, Christine et al. (2009) Role of computed tomography voxel size in detection and discrimination of calcium and iron deposits in atherosclerotic human coronary artery specimens. J Comput Assist Tomogr 33:517-22

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