Inflammation Alters Angiotensin Converting Enzymes (ACE and ACE-2) Balance in Rat Heart
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Angiotensin converting enzymes (ACE) and more recently discovered ACE-2 are important proteins involved in the renin–angiotensin system. The balance between ACE and ACE-2 is important for the regulation of blood pressure and electrolyte homeostasis. Inflammatory diseases like rheumatoid arthritis are associated with increased risk for cardiovascular complications. We studied the effect of inflammation on the expression levels of ACE and ACE-2 in two groups (n = 4/group) of adjuvant arthritis (AA) and healthy (control) rats. The AA group received 0.2 ml of 50 mg ml−1 of Mycobacterium butyricum suspended in squalene into the tail base. On day 12, rats were euthanized and their organs (hearts, liver, kidney, and intestine) were excised. The mRNA of ACE and ACE-2 were determined by real-time polymerase chain reaction. ACE and ACE-2 protein expression in rat heart was determined by Western blot. Inflammation resulted in 80% reduction of ACE-2 gene expression in rat heart. ACE-2/ACE expression ratio was significantly reduced from 0.7 ± 0.4 in control rats to 0.07 ± 0.09 in AA. Similarly, ACE-2/ACE protein expression ratio was also disrupted with a significant reduction in AA animals (6.7 ± 4.8 vs. 0.9 ± 05 in control and AA, respectively). ACE-2 has been found to provide negative feedback of renin–angiotensin system and protection of the heart and kidneys. Disruption of the balance between ACE and ACE-2 observed in inflammation may be, at least in part, involved in the cardiovascular complications seen in patients with inflammatory diseases.
KEY WORDSinflammation cardiac function experimental arthritis ACE ACE-2 angiotensin converting enzymes
Conflict of Interest
The study was supported by the Canadian Institute of Health Research (CIHR).
- 2.Wallberg-Jonsson, S., H. Johansson, M.L. Ohman, and S. Rantapaa-Dahlqvist. 1999. Extent of inflammation predicts cardiovascular disease and overall mortality in seropositive rheumatoid arthritis. A retrospective cohort study from disease onset. The Journal of Rheumatology 26(12): 2562–71.PubMedGoogle Scholar
- 14.Lambert, D.W., M. Yarski, F.J. Warner, P. Thornhill, E.T. Parkin, A.I. Smith, et al. 2005. Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2). The Journal of Biological Chemistry 280(34): 30113–30119.PubMedCrossRefGoogle Scholar