Abstract 17551: Protein Tyrosine Phosphatase-1B Deletion in Mice Improves Cardiac and Endothelial Functions During Aging
Cardiovascular aging is associated with left ventricular (LV) hypertrophy, myocardial fibrosis and endothelial dysfunction contributing to progressive heart failure. Our laboratory previously showed that Protein Tyrosine Phosphatase 1B (PTP1B) deletion in mice confers cardiac and endothelial protection in a post-infarction heart failure model. However, whether PTP1B deletion could slow aging-associated cardiovascular damages remains unknown.
We assessed LV function by echocardiography in wild-type (WT) or PTP1B-/- mice aged 3 to 18 months. We found an aging-dependent decrease in LV fractional shortening that was smaller in PTP1B-/- mice (-54% WT vs. -29% PTP1B-/-, p<0.001). Furthermore, the aging-induced LV diastolic dysfunction evidenced by the modification of the echocardiographic E/A parameter was significantly improved in PTP1B-/- mice. At 18 months, LV function assessed by an invasive procedure that allows measuring pressure-volume relationships (PVR), showed improved LV End-Systolic and LV End-Diastolic functional parameters in PTP1B-/- mice (LVESPVR, WT vs. PTP1B-/-: 13.9±0.9 vs. 18.4±1.6 mmHg/RVU, p<0.05 and LVEDPVR, WT vs. PTP1B-/-: 5.1±0.8 vs. 1.2±0.3 mmHg/RVU, p<0.01). Moreover, aging-induced cardiac hypertrophy and fibrosis were significantly reduced in PTP1B-/- animals (% cardiac collagen, WT vs. PTP1B-/- at 18months: 15.6±3.3 vs. 4.9±2.6, p<0.001), that also displayed higher myocardial capillary density. Interestingly, we also found that PTP1B mRNA expression was significantly enhanced in LV of aged WT mice suggesting its implication in cardiac aging.
Concerning the assessment of endothelial function, we found that PTP1B deletion partially restored flow-mediated dilatation of isolated mesenteric arteries (% dilatation at 200μL/min, WT vs. PTP1B-/-: -0.4±2.1 vs. 7.4±2.6, p<0.05) and improved relaxations of isolated coronary arteries in response to insulin (% relaxation at 10-6M insulin, WT vs. PTP1B-/-: 15±4 vs 24±3).
Taken together, our results show that PTP1B deletion improved cardiac function in association with an enhanced endothelial function in aging mice.
- © 2013 by American Heart Association, Inc.