Pressure overload by suprarenal aortic constriction in mice leads to left ventricular hypertrophy without c-Kit expression in cardiomyocytes

• Type of Material: Article
• Authors: Amy M. Nicks, Victor Chang Cardiac Research Institute; Scott H. Kesteven, Victor Chang Cardiac Research Institute; Ming Li, Victor Chang Cardiac Research Institute; Jianxin Wu, Victor Chang Cardiac Research Institute; Andrea Y. Chan, Victor Chang Cardiac Research Institute; Nawazish Naqvi, Emory University; Ahsan Husain, Emory University; Michael P. Feneley, Victor Chang Cardiac Research Institute; Nicola J. Smith, Victor Chang Cardiac Research Institute; Siiri E. Iismaa, Victor Chang Cardiac Research Institute; Robert M. Graham, Victor Chang Cardiac Research Institute
• Language: English
• Date: 2020-09-18
• Publisher: NATURE RESEARCH
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2020
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41598-020-72273-3
• Title of Journal or Parent Work: SCIENTIFIC REPORTS
• Volume: 10
• Issue: 1
• Start Page: 15318
• End Page: 15318
• Grant/Funding Information: This work was supported by National Health and Medical Research Council of Australia Grants [Grant numbers 573732 to RMG, MPF; 1074386 to RMG], National Heart Foundation of Australia Grant [Grant number G10S 5148 to RMG, SEI, ML], R.T. Hall Trust grant [RMG, SEI, ML, AN], Stem Cells Australia–the Australian Research Council Special Research Initiative in Stem Cell Science [Grant number SR110001002 to RMG], a Leducq Transatlantic Network of Excellence in Cardiovascular Research grant [RMG, AH] and a National Nature Science Foundation of China Grant [Grant number 81670336 to ML].
• Keywords: CARDIAC STEM-CELLS; DYSFUNCTION; CORONARY-ARTERIES; HEART-FAILURE; Multidisciplinary Sciences; SUFFICIENT; C-KIT(+) CELLS; ANIMAL-MODELS; HYPERTENSION; Science & Technology; REGENERATION; REASSESSMENT; Science & Technology - Other Topics
• Research Categories: Health Sciences, Medicine and Surgery; Biology, Cell

Abstract

Animal models of pressure overload are valuable for understanding hypertensive heart disease. We characterised a surgical model of pressure overload-induced hypertrophy in C57BL/6J mice produced by suprarenal aortic constriction (SAC). Compared to sham controls, at one week post-SAC systolic blood pressure was significantly elevated and left ventricular (LV) hypertrophy was evident by a 50% increase in the LV weight-to-tibia length ratio due to cardiomyocyte hypertrophy. As a result, LV end-diastolic wall thickness-to-chamber radius (h/R) ratio increased, consistent with the development of concentric hypertrophy. LV wall thickening was not sufficient to normalise LV wall stress, which also increased, resulting in LV systolic dysfunction with reductions in ejection fraction and fractional shortening, but no evidence of heart failure. Pathological LV remodelling was evident by the re-expression of fetal genes and coronary artery perivascular fibrosis, with ischaemia indicated by enhanced cardiomyocyte Hif1a expression. The expression of stem cell factor receptor, c-Kit, was low basally in cardiomyocytes and did not change following the development of robust hypertrophy, suggesting there is no role for cardiomyocyte c-Kit signalling in pathological LV remodelling following pressure overload.