Journal
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Volume 302, Issue 8, Pages H1667-H1682Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.01027.2011
Keywords
obesity; cardiovascular disease; exercise; activity
Funding
- National Institutes of Health (NIH) [1-R01-HL-073101-02, R24-RR-017718, RO1-DK-077200]
- Veterans Affairs Merit System Grant [0018]
- Veterans Affairs Biomolecular Imaging Center at the Harry S. Truman Veterans Affairs Hospital
- University of Missouri (Columbia, MO)
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DeMarco VG, Johnson MS, Ma L, Pulakat L, Mugerfeld I, Hayden MR, Garro M, Knight W, Britton SL, Koch LG, Sowers JR. Overweight female rats selectively breed for low aerobic capacity exhibit increased myocardial fibrosis and diastolic dysfunction. Am J Physiol Heart Circ Physiol 302: H1667-H1682, 2012. First published February 17, 2012; doi: 10.1152/ajpheart.01027.2011.-The statistical association between endurance exercise capacity and cardiovascular disease suggests that impaired aerobic metabolism underlies the cardiovascular disease risk in men and women. To explore this connection, we applied divergent artificial selection in rats to develop low-capacity runner (LCR) and high-capacity runner (HCR) rats and found that disease risks segregated strongly with low running capacity. Here, we tested if inborn low aerobic capacity promotes differential sex-related cardiovascular effects. Compared with HCR males (HCR-M), LCR males (LCR-M) were overweight by 34% and had heavier retroperitoneal, epididymal, and omental fat pads; LCR females (LCR-F) were 20% heavier than HCR females (HCR-F), and their retroperitoneal, but not perireproductive or omental, fat pads were heavier as well. Unlike HCR-M, blood pressure was elevated in LCR-M, and this was accompanied by left ventricular (LV) hypertrophy. Like HCR-F, LCR-F exhibited normal blood pressure and LV weight as well as increased spontaneous cage activity compared with males. Despite normal blood pressures, LCR-F exhibited increased myocardial interstitial fibrosis and diastolic dysfunction, as indicated by increased LV stiffness, a decrease in the initial filling rate, and an increase in diastolic relaxation time. Although females exhibited increased arterial stiffness, ejection fraction was normal. Increased interstitial fibrosis and diastolic dysfunction in LCR-F was accompanied by the lowest protein levels of phosphorylated AMP-actived protein kinase [phospho-AMPK (Thr(172))] and silent information regulator 1. Thus, the combination of risk factors, including female sex, intrinsic low aerobic capacity, and overweightness, promote myocardial stiffness/fibrosis sufficient to induce diastolic dysfunction in the absence of hypertension and LV hypertrophy.
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