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Rats are Protected from Chronic Pressure Overload Compared with Mice Through Angiogenesis, but not Myogenesis.
Author(s) -
Nishimura Koichi,
Oydanich Marko,
Zhang Jie,
Babici Denis,
Fraidenraich Diego,
Galindo Cristi,
Vatner Dorothy E,
Vatner Stephen
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.04074
Subject(s) - pressure overload , angiogenesis , medicine , myogenesis , muscle hypertrophy , endocrinology , cardiology , ejection fraction , cardiac function curve , blood pressure , ventricular remodeling , myocyte , heart failure , cardiac hypertrophy
It is generally assumed that rats and mice respond to cardiovascular stress similarly. The first goal of this investigation was to compare the effects of chronic pressure overload, induced by 4 weeks of transverse aortic constriction (TAC), in Sprague Dawley rats and C57/BL/6J mice. TAC, after 1 day, induced similar left ventricular (LV) pressure gradients in both rats and mice (113 ± 5.4 vs. 103 ± 11.5 mmHg), and after 4weeks a similar amount of LV hypertrophy (LV/tibial length increase: 51 ± 6.0 vs. 51 ± 5.7). After 4 weeks of TAC, LV systolic and diastolic function were preserved in rats, whereas LV ejection fraction decreased in mice (19 ± 2%), along with increases in LV end diastolic pressure (159 ± 54%), LV systolic wall stress (90 ± 12%), and LV diastolic wall stress (102 ± 41%). The second goal was to determine whether angiogenesis or myogenesis was the mechanism protecting against chronic pressure overload. Immunofluorescent Ki67 staining of capillaries revealed greater increases in angiogenesis with TAC in rats (10 ± 2 positive cells/field) than in mice (6 ± 1 positive cells/field). Myocardial blood flow fell by 55 ± 15% in mice but was preserved in rats. Coronary reserve, the increase in blood flow to the heart with adenosine, was preserved in rats, whereas it fell by 28% in mice with TAC. The next goal was to determine if myogenesis, through generation of stem cells, mediated these differences. This was accomplished by staining the myocardium with c‐kit. More c‐kit positive cells were found in rats with TAC compared to mice with TAC (0.30 ± 0.03 vs. 0.07 ± 0.02 cells/mm 2 ). Surprisingly, these c‐kit positive cells were located not in myocytes, but in the interstitial space and were all negative for Troponin I. However, some of these c‐kit positive cells were positive for CD31, i.e., endothelial cells, which could be involved in mediation of the angiogenesis. Thus, rats tolerate severe pressure overload better than mice, with mechanisms involving increased angiogenesis, but not myogenesis.