The arterial wall and arterial valves are complex structures. One of the major elements of these structures is the macromolecular scaffold that provides the strength and flexibility to perform the task in hand either retaining the blood in vessels against the arterial pressure or maintaining pressure via the function of coronary valves. In the last several years it has become apparent that the actual microstructure and composition of these macromolecules could influence the progress of different disease states most notably atherosclerosis and value calcification. To gain a better understanding of this process, we have embarked on studies to understand the fine structure of the macromolecules in arterial vascular bed using a novel optical imaging technique that relies on the non-linear excitation (NLE) of collagen and elastin to provide sub-micron images of their structure in unfixed fresh samples together with direct measures oflow density lipoprotein particles (LDL) binding using fluorescence microscopy and conventional histology methods. Over the last year we have made the following progress: 1) Following our previous demonstration that the exclusion of the elastin protective layer over the proteoglycans/collagen at arterial branch points in the coronary and mesenteric arteries, we focused on the renal artery entry into the aorta due to its large size and clinically important site of atherosclerosis. Surprisingly, we found that a novel macromolecular structure was discovered on the caudal surface of the renal artery ostium that essentially diverted aortic blood flow into the renal artery. This diverter was characterized as a collagen and proteoglycan containing protrusion into the aortic lumen without any significant elastic coating. As predicted from our earlier studies, we found this structure to selectively bind LDL over other regions of the arterial structures in this area consistent with the clinically described origin of renal artery atherosclerosis. We also demonstrated that this diverter significantly alters renal artery arterial flow using high resolution Doppler ultrasound, in vivo. We speculate that this diverter plays a significant role in the modulation of renal artery blood flow and that due to its macromolecular composition it contributes to the susceptibility of the caudal aspect of the renal artery ostium to atherosclerosis. We are currently performing multiple protein and proteoglycan screens of this tissue structure to attempt to find the proteins or macromolecules responsible for the selective LDL binding. 2) We reasoned that this diverter found at the opening of the renal artery may have a similar macromolecular structure as the coronary aortic valve. We have recently applied similar approaches to the evaluation of the aortic value leaflet macromolecular structures and found that the aortic surface of the valve that is susceptible to calcification has a distinctly different molecular structure than the surface facing the ventricle cavity. These initial results suggest that, again, the macromolecular structures of the aortic valve may contribute to the differential sensitivity of these two portions of the value to calcification. We are currently refining our measurements in the aortic valve leaflet macromolecular structure and composition that will include the determination of the relative extent of LDL binding. These studies may provide basic and clinical insight into the mechanisms of and susceptibilities to numerous coronary valve diseases.
