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

作者：Reed Alana L; Tanaka Atsuko; Sorescu Dan; Liu Hong; Jeong Euy Myoung; Sturdy Megan; Walp Erik R; Dudley Samuel C Jr; Sutliff Roy L^*

来源：American Journal of Physiology - Heart and Circulatory Physiology, 2011, 301(3): H824-H831.

DOI：10.1152/ajpheart.00407.2010

• heart failure
• transforming growth factor
• aging

Reed AL, Tanaka A, Sorescu D, Liu H, Jeong EM, Sturdy M, Walp ER, Dudley SC Jr, Sutliff RL. Diastolic dysfunction is associated with cardiac fibrosis in the senescence-accelerated mouse. Am J Physiol Heart Circ Physiol 301: H824-H831, 2011. First published July 1, 2011; doi:10.1152/ajpheart.00407.2010.-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-beta 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.

• 出版日期2011-9