Abstract
MOLECULAR PERSPECTIVES OF VASCULAR WALL STRUCTURE AND DISEASE: THE ELASTIC COMPONENT DAN W. URRY* Introduction In 1974 more than 50 percent of all deaths in the United States were caused by the major cardiovascular diseases [I]. Thus the ancient dictum that "a man is as old as his arteries" is even more applicable to longevity in our modern Western society. With past analytical developments utilized in biomedical research, the primary site within the vascular wall of two of the three major degenerative processes has been identified as the elastic fiber. This has led to an extension of the above statement. "It is true that we have the age of our arteries. This means more or less that we have the age of their elastic fibers" [2]. More recently, composite elements of the elastic fiber have been described in molecular detail [3, 4]. These molecular descriptions provide an understanding of the mechanism of pathological calcification of the elastic fiber [5] and of deleterious lipid deposition in this essential dynamic component of vascular wall [6]; they provide an understanding of the importance of temperature in the formation and repair of elastic fiber [7]; and they may provide a molecular rationale for relating elevated sodium chloride levels to elevated blood pressures [7]. The molecular perspectives derive from physicochemical methods and concepts applied in studying the structure and disease ofvascular wall elastic fiber. In the present review, after placing the vascular elastic fiber in anatomical perspective, the structure of the core of the elastic fiber is discussed in terms of the preferred intramolecular hydrogen bonding of repeating peptide units and in terms of dominant intermolecular inter- *Laboratory of Molecular Biophysics and the Cardiovascular Research and Training Center, University of Alabama Medical Center, Birmingham, Alabama 35294. I gratefully acknowledge Harriet Dustan for stimulating our investigations into the effects of NaCl and past and present members of the Laboratory of Molecular Biophysics for their essential contributions to this research. This work was supported in part by NIH grant HL-1 1310.© 1978 by The University of Chicago. 003 1-5982/78/2 102-0009$0 1.00 Perspectives in Biology and Medicine · Winter 1978 | 265 actions which occur as a result of the preferred intramolecular hydrogen bonding. It is from these interactions that elastomeric function becomes clarified and, with added information such as the role of temperature and the specific means whereby calcium ion is bound by polypeptide, that an understanding of the disease processes of the elastic fiber is obtained. With knowledge of molecular structure and interactions comes the capability of preparing synthetic elastomers, prosthetic materials, which may be developed as artificial components for vascular wall. Even the elucidation of molecular details of pathology, such as pathological calcification , has the potential of providing useful prosthetic materials. A serum calcified synthetic matrix, derived in the process of verifying the mechanism of vascular calcification, has striking similarity to the crystalline structure of bone and, as such, has the potential for development in applications such as periodontal disease or other uses where bone reconstruction is desired. Arterial Elastic Fiber The arterial wall (see fig. 1) is divided into three major regions—the intima, the media, and the adventitia—which are delimited by two relatively dense bands of connective tissue—the internal elastic lamina and the external elastic lamina. In addition to the two concentrated bands, connective tissue occurs throughout the vascular wall. The internal elastic lamina is the dominant concentration of connective tissue. It is comprised ofelastic fibers which at usual magnification in electron micrographs are seen as amorphous structures and of collagen fibers which are seen as banded structures in electron micrographs [8]. This is shown in figure 2. The relative amounts of collagen and of elastin, the protein of elastic fibers, change throughout the arterial tree with there being about twice as much elastin as collagen in the aortic arch and the descending thoracic aorta, that is, in the arteries most proximal to the heart where elasticity is most required, and there being less elastin than collagen in the smaller vessels [9]. Elastin commonly occurs in the vascular wall as 5-6-/u.m diameter fibers (see fig. 3) with a coating of microfibrils with diameters...