Angiotensin-II Receptor Type Ia Does Not Contribute to Cardiac Atrophy Following High-Thoracic Spinal Cord Injury in Mice
Järve Anne, Fatimunnisa Qadri, Mihail Todiras, Shirley Schmolke, Michael Bader
Spinal cord injury (SCI) leads to cardiac atrophy often accompanied by functional deficits. The renin–angiotensin system (RAS) with angiotensin II (AngII) signalling via its receptor AT1a might contribute to cardiac atrophy post-SCI. We performed spinal cord transection at thoracic level T4 (T4-Tx) or sham-operation in female wild-type mice (WT, n = 27) and mice deficient in AT1a (Agtr1a−/−, n = 27). Echocardiography (0, 7, 21 and 28 days post-SCI) and histology and gene expression analyses at 1 and 2 months post-SCI were performed. We found cardiac atrophy post-SCI: reduced heart weight, reduced estimated left ventricular mass in Agtr1a−/−, and reduced cardiomyocyte diameter in WT mice. Although, the latter as well as stroke volume (SV) and cardiac output (CO) were reduced in Agtr1a−/− mice already at baseline, cardiomyocyte diameter was even smaller in injured Agtr1a−/− mice compared to injured WT mice. SV and CO were reduced in WT mice post-SCI. Ejection fraction and fractional shortening were preserved post-SCI in both genotypes. There were no histological signs of fibrosis and pathology in the cardiac sections of either genotype post-SCI. Gene expression of Agtr1a showed a trend for up-regulation at 2 months post-SCI; angiotensinogen was up-regulated at 2 month post-SCI in both genotypes. AngII receptor type 2 (Agtr2) was up- and down-regulated at 1 and 2 months post-SCI in WT mice, respectively, and Ang-(1-7) receptor (Mas) at 1 and 2 months post-SCI. Atrogin-1/MAFbx and MuRF1, atrophy markers, were not significantly up-regulated post-SCI. Our data show that lack of AT1a does not protect from cardiac atrophy post-SCI.