在患有心脏病的犬中，血浆和组织血管紧张素转换酶 2 活性以及血管紧张素肽的血浆平衡浓度。
Plasma and tissue angiotensin-converting enzyme 2 activity and plasma equilibrium concentrations of angiotensin peptides in dogs with heart disease.
机构信息
Department of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
出版信息
J Vet Intern Med. 2019 Jul;33(4):1571-1584. doi: 10.1111/jvim.15548. Epub 2019 Jun 28.
BACKGROUND
Angiotensin-converting enzyme 2 (ACE2) is a homologue of angiotensin-converting enzyme (ACE) and produces angiotensin peptides (APs), such as angiotensin 1-9 and 1-7 that are vasodilatory and natriuretic, and act to counterbalance angiotensin II.
HYPOTHESIS
Evidence of ACE2 can be found in tissues and plasma of dogs. Equilibrium concentrations of renin angiotensin aldosterone system (RAAS) APs differ in dogs with heart disease compared to healthy dogs and recombinant human ACE2 (rhACE2) alters relative concentrations of APs.
ANIMALS
Forty-nine dogs with and 34 dogs without heart disease.
METHODS
Immunohistochemistry and assays for tissue and plasma ACE2 activity and equilibrium concentrations of plasma RAAS APs were performed.
RESULTS
Immunolabeling for ACE2 was present in kidney and myocardial tissue. Median plasma ACE2 activity was significantly increased in dogs with congestive heart failure (CHF; 6.9 mU/mg; interquartile range [IQR], 5.1-12.1) as compared to control (2.2 mU/mg; IQR, 1.8-3.0; P = .0003). Plasma equilibrium analysis of RAAS APs identified significant increases in the median concentrations of beneficial APs, such as angiotensin 1-7, in dogs with CHF (486.7 pg/mL; IQR, 214.2-1168) as compared to those with preclinical disease (41.0 pg/mL; IQR, 27.4-45.1; P < .0001) or control (11.4 pg/mL; IQR, 7.1-25.3; P = .01). Incubation of plasma samples from dogs with CHF with rhACE2 increased beneficial APs, such as angiotensin 1-9 (preincubation, 10.3 pg/mL; IQR, 4.4-37.2; postincubation, 2431 pg/mL; IQR, 1355-3037; P = .02), while simultaneously decreasing maladaptive APs, such as angiotensin II (preincubation, 53.4 pg/mL; IQR, 28.6-226.4; postincubation, 2.4 pg/mL; IQR, 0.50-5.8; P = .02).
CONCLUSIONS AND CLINICAL IMPORTANCE
Recognition of the ACE2 system expands the conventional view of the RAAS in the dog and represents an important potential therapeutic target.
背景
血管紧张素转换酶 2（ACE2）是血管紧张素转换酶（ACE）的同源物，可产生血管紧张素肽（APs），如血管紧张素 1-9 和 1-7，具有血管扩张和利钠作用，并能对抗血管紧张素 II。
假说
在患有心脏病的犬的组织和血浆中可以发现 ACE2。与健康犬相比，患有心脏病的犬的肾素血管紧张素醛固酮系统（RAAS）APs 的平衡浓度存在差异，重组人 ACE2（rhACE2）改变了 APs 的相对浓度。
动物
49 只患有心脏病的犬和 34 只没有心脏病的犬。
方法
进行了组织和血浆 ACE2 活性以及血浆 RAAS APs 平衡浓度的免疫组织化学和检测。
结果
在肾脏和心肌组织中均存在 ACE2 的免疫标记。与对照组（2.2 mU/mg；IQR，1.8-3.0；P =.0003）相比，充血性心力衰竭（CHF）犬的血浆 ACE2 活性中位数明显升高（6.9 mU/mg；IQR，5.1-12.1）。通过对 RAAS APs 的血浆平衡分析，发现 CHF 犬的有益 AP 浓度中位数显著升高，如血管紧张素 1-7（486.7 pg/mL；IQR，214.2-1168），与临床前疾病犬（41.0 pg/mL；IQR，27.4-45.1；P < .0001）或对照组（11.4 pg/mL；IQR，7.1-25.3；P =.01）相比。用 rhACE2 孵育 CHF 犬的血浆样本增加了有益的 AP，如血管紧张素 1-9（孵育前，10.3 pg/mL；IQR，4.4-37.2；孵育后，2431 pg/mL；IQR，1355-3037；P =.02），同时降低了有害的 AP，如血管紧张素 II（孵育前，53.4 pg/mL；IQR，28.6-226.4；孵育后，2.4 pg/mL；IQR，0.50-5.8；P =.02）。
结论和临床意义
对 ACE2 系统的认识扩展了犬 RAAS 的传统观点，代表了一个重要的潜在治疗靶点。
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