Evidence supporting the hypothesis that age-associated changes in cardiovascular structure/function are implicated in the markedly increased risk for cardiovascular disease in older persons has been presented in the preceding 2 articles in this series.1,2 It follows that therapies to prevent or delay cardiovascular changes that accompany aging may reduce the risk for age-associated cardiovascular diseases. Understanding the nature and effectiveness of such therapies, however, requires an understanding of heart and arterial aging at the cellular and molecular levels. Fortunately, many of the age-associated changes in cardiac and arterial structure or function that have been observed in humans also occur across a wide range of other species. Insights gained from cellular and molecular studies in these animal models may hold clues that will assist in directing future efforts toward developing novel therapies for age-associated arterial and cardiac structural and functional remodeling in humans.

Age-associated remodeling of the walls of large arteries of rodents (Table 1) and nonhuman primates is quite similar to that observed in humans and includes luminal dilation, intimal and medial thickening (Figure 1), vascular stiffening, and endothelial dysfunction.3–7 

View this table:

TABLE 1. Age-Associated Aortic Changes in Rodents 





Figure 1. A, Morphometric changes in the aortic wall of rats showing significant aortic intimal thickening in old rats (upper), as compared with young rats (lower). m indicates media; a, adventitia. Arrows show the internal elastic lamina. Reprinted from reference 4. B, Representative aortic sections from 2-month, 8-month, and 30-month-old rats stained with an antibody against MMP-2 and MT1-MMP, a tissue activator for MMP-2. The antibody stains brown. L indicates lumen, m, media. Reprinted from reference 7. C, Representative examples of in vivo zymography in aortae of 2-month, 8-month, and 30-month-old rats. Control (left) reactive zymograms (right) and reactive zymograms after coincubation with a reactive buffer. Inset in lower …

Arterial and cardiac aging: Major shareholders in cardiovascular disease enterprises. Part III: Cellular and molecular clues to heart and arterial aging

Devices formed of or including biocompatible polyhydroxyalkanoates are provided with controlled degradation rates, preferably less than one year under physiological conditions. Preferred devices include sutures, suture fasteners, meniscus repair devices, rivets, tacks, staples, screws (including interference screws), bone plates and bone plating systems, surgical mesh, repair patches, slings, cardiovascular patches, orthopedic pins (including bone filling augmentation material), adhesion barriers, stents, guided tissue repair/regeneration devices, articular cartilage repair devices, nerve guides, tendon repair devices, atrial septal defect repair devices, pericardial patches, bulking and filling agents, vein valves, bone marrow scaffolds, meniscus regeneration devices, ligament and tendon grafts, ocular cell implants, spinal fusion cages, skin substitutes, dural substitutes, bone graft substitutes, bone dowels, wound dressings, and hemostats. The polyhydroxyalkanoates can contain additives, be formed of mixtures of monomers or include pendant groups or modifications in their backbones, or can be chemically modified, all to alter the degradation rates. The polyhydroxyalkanoate compositions also provide favorable mechanical properties, biocompatibility, and degradation times within desirable time frames under physiological conditions.

Medical devices and applications of polyhydroxyalkanoate polymers

Water soluble macromers are modified by addition of free radical polymerizable groups, such as those containing a carbon-carbon double or triple bond, which can be polymerized under mild conditions to encapsulate tissues, cells, or biologically active materials. The polymeric materials are particularly useful as tissue adhesives, coatings for tissue lumens including blood vessels, coatings for cells such as islets of Langerhans, coatings, plugs, supports or substrates for contact with biological materials such as the body, and as drug delivery devices for biologically active molecules.

Gels for encapsulation of biological materials

Hydrogels of polymerized and crosslinked macromers comprising hydrophilic oligomers having biodegradable monomeric or oligomeric extensions, which biodegradable extensions are terminated on free ends with end cap monomers or oligomers capable of polymerization and cross linking are described. The hydrophilic core itself may be degradable, thus combining the core and extension functions. Macromers are polymerized using free radical initiators under the influence of long wavelength ultraviolet light, visible light excitation or thermal energy. Biodegradation occurs at the linkages within the extension oligomers and results in fragments which are non-toxic and easily removed from the body. Preferred applications for the hydrogels include prevention of adhesion formation after surgical procedures, controlled release of drugs and other bioactive species, temporary protection or separation of tissue surfaces, adhering of sealing tissues together, and preventing the attachment of cells to tissue surfaces.

Photopolymerizable biodegradable hydrogels as tissue contacting materials and controlled-release carriers

Background— The functional changes associated with cellular senescence may be involved in human aging and age-related vascular disorders. We have shown the important role of telomere and telomerase in vascular cell senescence in vitro. Progressive telomere shortening in vivo has been observed in the regions susceptible to atherosclerosis, implying contributions to atherogenesis. However, whether senescent vascular cells are present in the vasculature and contribute to the pathogenesis of atherosclerosis remains unclear. Methods and Results— Senescence-associated β-galactosidase (β-gal) activity was examined in the coronary arteries and the internal mammary arteries retrieved from autopsied individuals who had had ischemic heart diseases. Strong β-gal stainings were observed in atherosclerotic lesions of the coronary arteries but not in the internal mammary arteries. An immunohistochemical analysis using anti-factor VIII antibody demonstrated that β-gal stained cells are vascular endothelial cells. To dete...

Endothelial cell senescence in human atherosclerosis: role of telomere in endothelial dysfunction.

http://directory.umm.ac.id/Data%20Elmu/jurnal/A/Atherosclerosis/Vol152.Issue2.Oct2000/7171.pdf

Telomere attrition of the human abdominal aorta: relationships with age and atherosclerosis.

New outlook on pericardial substitution after open heart operations.

Cytologic examination of peritoneal fluid showed only malignant squamous cells, without revealing adenocarcinomatous cell components, in a patient who had an endometrioid adenosquamous-cell carcinoma of the ovary. Histologic examination of the ovary demonstrated diffuse squamous-cell carcinoma with rare foci of endometrioid and abortive malignant glands, as well as isolated mucin-positive cells. The cytologic differential diagnosis of malignant squamous cells in peritoneal fluid and the pathogenesis of squamous-cell carcinoma of the ovary are discussed.

M.Yusuf Khan

Papers

Telomere attrition of the human abdominal aorta: relationships with age and atherosclerosis.

New outlook on pericardial substitution after open heart operations.

Adenosquamous-cell carcinoma of the ovary: report of a case with positive peritoneal fluid cytology.