About this item:

607 Views | 0 Downloads

Author Notes:

Address for reprint requests and other correspondence: R. L. Sutliff, Emory Univ./Atlanta VAMC, Rm. 12C-173 (Mailstop 151-P), 1670 Clairmont Rd., Decatur, GA 30033 (e-mail: rsutlif@emory.edu).

Subject:

Research Funding:

Support for this study was provided by National Institutes of Health Grants R01-HL-070892 (to R. L. Sutliff); R01-HL-085558, R01-HL-073753, and P01-HL-058000 (to S. C. Dudley, Jr.); and T32-ES-012870 (to A. L. Reed).

Keywords:

  • heart failure
  • transforming growth factor
  • aging

Diastolic dysfunction is associated with cardiac fibrosis in the senescence-accelerated mouse

Tools:

Journal Title:

AJP - Heart and Circulatory Physiology

Volume:

Volume 301, Number 3

Publisher:

, Pages H824-H831

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Diastolic heart failure is a major cause of mortality in the elderly population. It is often preceded by diastolic dysfunction, which is characterized by impaired active relaxation and increased stiffness. We tested the hypothesis that senescence-prone (SAMP8) mice would develop diastolic dysfunction compared with senescence-resistant controls (SAMR1). Pulsed-wave Doppler imaging of the ratio of blood flow velocity through the mitral valve during early (E) vs. late (A) diastole was reduced from 1.3 ± 0.03 in SAMR1 mice to 1.2 ± 0.03 in SAMP8 mice (P < 0.05). Tissue Doppler imaging of the early (E') and late (A') diastolic mitral annulus velocities found E' reduced from 25.7 ± 0.9 mm/s in SAMR1 to 21.1 ± 0.8 mm/s in SAMP8 mice and E'/A' similarly reduced from 1.1 ± 0.02 to 0.8 ± 0.03 in SAMR1 vs. SAMP8 mice, respectively (P < 0.05). Invasive hemodynamics revealed an increased slope of the end-diastolic pressure-volume relationship (0.5 ± 0.05 vs. 0.8 ± 0.14; P < 0.05), indicating increased left ventricular chamber stiffness. There were no differences in systolic function or mean arterial pressure; however, diastolic dysfunction was accompanied by increased fibrosis in the hearts of SAMP8 mice. In SAMR1 vs. SAMP8 mice, interstitial collagen area increased from 0.3 ± 0.04 to 0.8 ± 0.09% and perivascular collagen area increased from 1.0 ± 0.11 to 1.6 ± 0.14%. Transforming growth factor-β and connective tissue growth factor gene expression were increased in the hearts of SAMP8 mice (P < 0.05 for all data). In summary, SAMP8 mice show increased fibrosis and diastolic dysfunction similar to those seen in humans with aging and may represent a suitable model for future mechanistic studies.
Export to EndNote