Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.24.B1 (
angiotensin-converting enzyme 2
)
1,025
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The intermediate-conductance Ca
2+
-activated K
+
(K
Ca
3.1) channel plays a vital role in myocardial fibrosis induced by angiotensin (Ang) II. However, as the antagonists of Ang II, the effect of
angiotensin-converting enzyme 2
(
ACE2
)-angiotensin-(1-7)-Mas axis on K
Ca
3.1 channel during myocardial fibrosis remains unknown. This study was designed to explore the function of K
Ca
3.1 channel in the cardioprotective role of
ACE2
-Ang-(1-7)-Mas. Wild-type (WT) mice, hACE2 transgenic mice (Tg), and
ACE2
deficiency mice (
ACE2
-/-
) were administrated with Ang II by osmotic mini-pumps. As the activator of
ACE2
, diminazene aceturate (DIZE) inhibited increase of blood pressure, collagen deposition, and K
Ca
3.1 protein expression in myocardium of WT mice induced by Ang II. In Tg and
ACE2
-/-
mice, besides the elevation of blood pressure, Ang II induced transformation of cardiac fibroblast into myofibroblast and resulted in augmentation of hydroxyproline concentration and collagen deposition, as well as K
Ca
3.1 protein expression, but the changes in
ACE2
-/-
mice were more obvious than those in Tg mice. Mas antagonist A779 reduced blood pressure, myocardium fibrosis, and myocardium K
Ca
3.1 protein expression by Ang II in Tg mice, but activation of K
Ca
3.1 with SKA-31 in Tg mice promoted the pro-fibrogenic effects of Ang II. Respectively, in
ACE2
-/-
mice,
TRAM
-34, the K
Ca
3.1 blocker, and Ang-(1-7) inhibited increase of blood pressure, collagen deposition, and K
Ca
3.1 protein expression by Ang II. Moreover, DIZE and Ang-(1-7) depressed p-ERK1/2/t-ERK increases by Ang II in WT mice, and after blockage of ERK1/2 pathway with PD98059, the K
Ca
3.1 protein expression was reduced in WT mice. In conclusion, the present study demonstrates that
ACE2
-Ang-(1-7)-Mas protects the myocardium from hypertension-induced injury, which is related to its inhibiting effect on K
Ca
3.1 channels through ERK1/2 pathway. Our results reveal that K
Ca
3.1 channel is likely to be a critical target on the
ACE2
-Ang-(1-7)-Mas axis for its protective role in myocardial fibrosis and changes of K
Ca
3.1 induced by homeostasis of ACE-Ang II-AT1 axis and
ACE2
-Ang-(1-7)-Mas axis may be a new therapeutic target in myocardial fibrosis.
...
PMID:Protective role of ACE2-Ang-(1-7)-Mas in myocardial fibrosis by downregulating K
Ca
3.1 channel via ERK1/2 pathway. 2759 22
