Angiotensin-(1–7) Receptor Mas Deficiency Does Not Exacerbate Cardiac Atrophy Following High-Level Spinal Cord Injury in Mice

Abstract

Experimental spinal cord injury (SCI) causes a morphological and functional deterioration of the heart, in which the renin-angiotensin system (RAS) might play a role. The recently discovered non-canonical axis of RAS with angiotensin-(1-7) and its receptor Mas, which is associated with cardioprotection could be essential to prevent damage to the heart following SCI. We investigated the cardiac consequences of SCI and the role of Mas in female wild-type (WT, n = 22) and mice deficient of Mas (Mas −/− , n = 25) which underwent spinal cord transection at thoracic level T4 (T4-Tx) or sham-operation by echocardiography (0, 7, 21, and 28 days post-SCI), histology and gene expression analysis at 1 or 2 months post-SCI. We found left ventricular mass reduction with preserved ejection fraction (EF) and fractional shortening in WT as well as Mas −/− mice. Cardiac output was reduced in Mas −/− mice, whereas stroke volume (SV) was reduced in WT T4-Tx mice. Echocardiographic indices did not differ between the genotypes. Smaller heart weight (HW) and smaller cardiomyocyte diameter at 1 month post-SCI compared to sham mice was independent of genotype. The muscle-specific E3 ubiquitin ligases Atrogin-1/MAFbx and MuRF1 were upregulated or showed a trend for upregulation in WT mice at 2 months post-SCI, respectively. Angiotensinogen gene expression was upregulated at 1 month post-SCI and angiotensin II receptor type 2 downregulated at 2 month post-SCI in Mas −/− mice. Mas was downregulated post-SCI. Cardiac atrophy following SCI, not exacerbated by lack of Mas, is a physiological reaction as there were no signs of cardiac pathology and dysfunction.

Does Myocardial Atrophy Represent Anti-Arrhythmic Phenotype?

“…“The sedentary heart”, i.e., physical inactivity, is also associated with cardiac atrophy [ 46 ], in contrast to hypertrophy in trained athletes. A left ventricular mass reduction was reported following spinal cord injury [ 47 , 48 , 49 ] as well as in Alzheimer’s disease models induced in mice [ 50 ]. Experimental chronic alcohol exposure [ 51 ] and sepsis [ 52 ] also induced cardiac atrophy.…”

Clinic serum levels of Plin5 is therapeutic target of spinal cord injury and Plin5 reduced inflammation in spinal cord injury via silent information regulator 1 dependent inhibition of NLRP3 inflammasome

“…Spinal cord injury (SCI) can be divided into primary injury and secondary injury according to the molecular mechanism of pathogenesis (Gensel & Zhang, 2015). Primary SCI is caused by the direct or indirect action of initial external force on the spinal cord, while secondary SCI is caused by destructive lesions in the initially complete tissues surrounding primary SCI following a sequence of physiological and biochemical mechanisms, including apoptosis, oxidative stress and inflammatory response, further aggravating the degree of damage and expanding the scope of damage (Kjell & Olson, 2016;Järve et al, 2020). The post-SCI inflammatory response is relatively complex, involving both nerves and immune systems, and the dynamic role of various factors, all of which become important events that constitute secondary SCI (Kornhaber et al, 2018;Hoey & Hubscher, 2020).…”