Experimental Spinal Cord Injury Causes Left-Ventricular Atrophy and Is Associated with an Upregulation of Proteolytic Pathways.

Abstract

Spinal cord injury (SCI) causes autonomic dysfunction, altered neurohumoral control, profound hemodynamic changes, and an increased risk of heart disease. In this prospective study, we investigated the cardiac consequences of chronic experimental SCI in rats by combining cutting edge in vivo techniques (magnetic resonance imaging [MRI] and left-ventricular [LV] pressure-volume catheterization) with histological and molecular assessments. Twelve weeks post-SCI, MRI-derived structural indices and in vivo LV catheterization-derived functional indices indicated the presence of LV atrophy (LV mass in Control vs. SCI = 525 ± 38.8 vs. 413 ± 28.6 mg, respectively; p = 0.0009), reduced ventricular volumes (left-ventricular end-diastolic volume in Control vs. SCI = 364 ± 44 vs. 221 ± 35 μL, respectively; p = 0.0004), and contractile dysfunction (end-systolic pressure-volume relationship in Control vs. SCI = 1.31 ± 0.31 vs. 0.76 ± 0.11 mm Hg/μL, respectively; p = 0.0045). Cardiac atrophy and contractile dysfunction in SCI were accompanied by significantly lower blood pressure, reduced circulatory norepinephrine, and increased angiotensin II. At the cellular level, we found the presence of reduced cardiomyocyte size and increased expression of angiotensin II type 1 receptors and transforming growth factor-beta receptors (TGF-β receptor 1 and 2) post-SCI. Importantly, we found more than a two-fold increase in muscle ring finger-1 and Beclin-1 protein level following SCI, indicating the upregulation of the ubiquitin-proteasome system and autophagy-lysosomal machinery. Our data provide novel evidence that SCI-induced cardiomyocyte atrophy and systolic cardiac dysfunction are accompanied by an upregulation of proteolytic pathways, the activation of which is likely due to loss of trophic support from the sympathetic nervous system, neuromechanical unloading, and altered neurohumoral pathways.

• Authors: Malihe-Sadat Poormasjedi-Meibod, Maral Mansouri, Mary Fossey, Jordan W Squair, Jie Liu, John H McNeill, Christopher R West
• Journal: Journal of neurotrauma (J Neurotrauma) Vol. 36 Issue 6 Pg. 950-961 (03 19 2019) ISSN: 1557-9042 [Electronic] United States
• PMID: 29877162 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Topics

• Animals
• Atrophy (etiology)
• Disease Models, Animal
• Heart Ventricles (pathology)
• Male
• Proteolysis
• Rats
• Rats, Zucker
• Spinal Cord Injuries (complications, physiopathology)
• Up-Regulation
• Ventricular Dysfunction, Left (etiology, physiopathology)