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(Circulation. 2007;116:669-676.)
© 2007 American Heart Association, Inc.

Vascular Medicine

Mechanism of Gender-Specific Differences in Aortic Stiffness With Aging in Nonhuman Primates

Hongyu Qiu, MD, PhD; Christophe Depre, MD, PhD; Kaushik Ghosh, PhD; Ranillo G. Resuello, DVM; Filipinas F. Natividad, PhD; Franco Rossi, MSEE; Athanasios Peppas, BS; You-Tang Shen, MD; Dorothy E. Vatner, MD; Stephen F. Vatner, MD

From the Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry New Jersey, New Jersey Medical School, Newark (H.Q., C.D., F.R., A.P., Y.-T.S., D.E.V., S.F.V.); Department of Mathematical Sciences, New Jersey Institute of Technology, Newark (K.G.); Simian Conservation Breeding and Research Center, Inc, Manila, Philippines (R.G.R.); and St Luke’s Medical Center, Quezon City, Philippines (F.F.N.).

Correspondence to Stephen F. Vatner, MD, Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, 185 S Orange Ave, MSB G-609, Newark, NJ 07103. E-mail vatnersf{at}umdnj.edu

Received January 8, 2007; accepted June 7, 2007.

Background— Our hypothesis was that the changes in vascular properties responsible for aortic stiffness with aging would be greater in old male monkeys than old female monkeys.

Methods and Results— We analyzed the effects of gender differences in aging on in vivo measurements of aortic pressure and diameter and on extracellular matrix of the thoracic aorta in young adult (age, 6.6±0.5 years) versus old adult (age, 21.2±0.2 years) monkeys (Macaca fascicularis). Aortic stiffness, as represented by the pressure strain elastic modulus (Ep), increased more in old male monkeys (5.08±0.81; P<0.01) than in old females (3.06±0.52). In both genders, collagen density was maintained, collagen-bound glycation end products increased, and collagen type 1 decreased. However, elastin density decreased significantly (from 22±1.5% to 15±1.2%) with aging (P<0.05) only in males. Furthermore, only old males were characterized by a decrease (P<0.05) in collagen type 3 (an isoform that promotes elasticity) and an increase in collagen type 8 (an isoform that promotes the neointimal migration of vascular smooth muscle cells). In contrast to the data in monkeys, collagen types 1 and 3 both increased significantly in aging rats.

Conclusions— There are major species differences in the effects of aging on aortic collagen types 1 and 3. Furthermore, because alterations in collagen density, collagen content, hydroxyproline, and collagen advanced glycation end products were similar in both old male and female monkeys, these factors cannot be responsible for the greater increase in stiffness in old males. However, changes in collagen isoforms and the decrease in elastin observed only in old males likely account for the greater increase in aortic stiffness.

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