Inflammation Alters Angiotensin Converting Enzymes (ACE and ACE-2) Balance in Rat Heart

Abstract

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.

Ulinastatin activates the renin–angiotensin system to ameliorate the pathophysiology of severe acute pancreatitis

“…39 Further, Ang-(1-7) has been shown to have anti-inflammatory properties due to its antagonistic effects on Ang II, an important pro-inflammatory factor. 40,41 These data, together with results from the current study, suggest that the therapeutic effect of ulinastatin on cerulein and LPS-induced pancreatitis, are mediated via upregulation of the ACE2-Ang-(1-7)-Mas receptor axis of the RAS.…”

“…Ang‐(1–7), acting through Mas receptor, induces the release of nitric oxide through a phosphoinositide‐3 kinase/Akt‐dependent pathway, which in turn causes vasodilation, inhibition of cell growth, and counter‐regulation of the vasoconstriction and proliferative effects of activation of AT‐1R by Ang II . Further, Ang‐(1–7) has been shown to have anti‐inflammatory properties due to its antagonistic effects on Ang II, an important pro‐inflammatory factor . These data, together with results from the current study, suggest that the therapeutic effect of ulinastatin on cerulein and LPS‐induced pancreatitis, are mediated via upregulation of the ACE2‐Ang‐(1–7)–Mas receptor axis of the RAS.…”

Preservation of Glucagon-Like Peptide-1 Level Attenuates Angiotensin II-Induced Tissue Fibrosis by Altering AT1/AT2 Receptor Expression and Angiotensin-Converting Enzyme 2 Activity in Rat Heart

“…Although we did not measure plasma levels of GLP-1 and blood sugar, the doses selected for liraglutide and linagliptin are primarily based on previous observations showing that the GLP-1 level is maintained and glucose is controlled with these drugs [41][42][43][44]. In review of the present results, liraglutide or linagliptin is a potent protector against Ang II-induced cardiac fibrosis by providing exogenous GLP-1 or preserving endogenous GLP-1.…”

A snapshot of the Ixodes scapularis degradome

“…We would like to notify the reader here that, we have discussed aminopeptidase (AMP)-like enzymes in family M1 together with other AMP enzymes from other families as group below. In family M2, which is typified by the blood pressure regulating enzymes, angiotensin-converting enzymes (ACE) 1 and 2 (Hanafy et al, 2010), the I. scapularis genome encodes 4 putatively active and 2 non-protease MP enzyme homologs (table 4). None of the 4 putatively active I. scapularis family M2 enzymes have been provisionally identified and thus their potential role(s) in tick physiology are unknown.…”