Arterial and Cardiac Aging: Major Shareholders in Cardiovascular Disease Enterprises

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Abstract
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 …

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