Purification and characterization of angiotensin converting enzyme 2 (ACE2) from murine model of mesangial cell in culture

Angiotensin converting enzyme 2 (ACE2) is a component of the renin-angiotensin system (RAS) which converts Ang II, a potent vasoconstrictor peptide into Ang 1-7, a vasodilator peptide which may act as a negative feedback hormone to the actions of Ang II. The discovery of this enzyme added a new level of complexity to this system. The mesangial cells (MC) have multiple functions in glomerular physiology and pathophysiology and are able to express all components of the RAS. Despite of being localized in these cells, ACE2 has not yet been purified or characterized. In this study ACE2 from mice immortalized MC (IMC) was purified by ion-exchange chromatography. The purified enzyme was identified as a single band around 60-70 kDa on SDS-polyacrylamide gel and by Western blotting using a specific antibody. The optima pH and chloride concentrations were 7.5 and 200 mM, respectively. The N-terminal sequence was homologous with many species ACE2 N-terminal sequences as described in the literature. ACE2 purified from IMC was able to hydrolyze Ang II into Ang 1-7 and the K_m value for Ang II was determined to be 2.87 ± 0.76 μM. In conclusion, we purified and localized, for the first time, ACE2 in MC, which was able to generate Ang 1-7 from Ang II. Ang 1-7 production associated to Ang II degradation by ACE2 may exert a protective effect in the renal hemodynamic.     

Inhibition of MAPK‐mediated ACE expression by compound C66 prevents STZ‐induced diabetic nephropathy

A range of in vitro, experimental and clinical intervention studies have implicated an important role for hyperglycaemia‐induced activation of the renin‐angiotensin system (RAS) in the development and progression of diabetic nephropathy (DN). Blockade of RAS by angiotensin converting enzyme (ACE) inhibitors is an effective strategy in treating diabetic kidney diseases. However, few studies demonstrate the mechanism by which hyperglycaemia up‐regulates the expression of ACE gene. Our previous studies have identified a novel curcumin analogue, (2E,6E)‐2,6‐bis(2‐(trifluoromethyl)benzylidene)cyclohexanone (C66), which could inhibit the high glucose (HG)‐induced phosphorylation of mitogen‐activated protein kinases in mouse macrophages. In this study, we found that the renal protection of C66 in diabetic mice was associated with mitogen‐activated protein kinase (MAPK) inactivation and ACE/angiotensin II (Ang II) down‐regulation. Generally, MAPKs have been considered as a downstream signalling of Ang II and a mediator for Ang II‐induced pathophysiological actions. However, using C66 and specific inhibitors as small molecule probes, in vitro experiments demonstrate that the MAPK signalling pathway regulates ACE expression under HG stimulation, which contributes to renal Ang II activation and the development of DN. This study indicates that C66 is a potential candidate of DN therapeutic agents, and more importantly, that reduction in ACE expression by MAPKs inhibition seems to be an alternative strategy for the treatment of DN.     

ACE2 – From the renin–angiotensin system to gut microbiota and malnutrition

The renin–angiotensin system (RAS) is a complex network that regulates blood pressure, electrolyte and fluid homeostasis, as well as the function of several organs. Angiotensin-converting enzyme 2 (ACE2) was identified as an enzyme that negatively regulates the RAS by converting Ang II, the main bioactive molecule of the RAS, to Ang 1–7. Thus, ACE2 counteracts the role of angiotensin-converting enzyme (ACE) which generates Ang II from Ang I. ACE and ACE2 have been implicated in several pathologies such as cardiovascular and renal disease or acute lung injury. In addition, ACE2 has functions independent of the RAS: ACE2 is the receptor for the SARS coronavirus and ACE2 is essential for expression of neutral amino acid transporters in the gut. In this context, ACE2 modulates innate immunity and influences the composition of the gut microbiota, which can explain diarrhea and intestinal inflammation observed in Hartnup disorder, Pellagra, or under conditions of severe malnutrition. Here we review and discuss the diverse functions of ACE2 and its relevance to human pathologies.     

ACE2 deficiency enhances angiotensin II-mediated aortic profilin-1 expression, inflammation and peroxynitrite production

Inflammation and oxidative stress play a crucial role in angiotensin (Ang) II-mediated vascular injury. Angiotensin-converting enzyme 2 (ACE2) has recently been identified as a specific Ang II-degrading enzyme but its role in vascular biology remains elusive. We hypothesized that loss of ACE2 would facilitate Ang II-mediated vascular inflammation and peroxynitrite production. 10-week wildtype (WT, Ace2(+/y)) and ACE2 knockout (ACE2KO, Ace2(-/y)) mice received with mini-osmotic pumps with Ang II (1.5 mg.kg?1.d?1) or saline for 2 weeks. Aortic ACE2 protein was obviously reduced in WT mice in response to Ang II related to increases in profilin-1 protein and plasma levels of Ang II and Ang-(1-7). Loss of ACE2 resulted in greater increases in Ang II-induced mRNA expressions of inflammatory cytokines monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-1β, and IL-6 without affecting tumor necrosis factor-α in aortas of ACE2KO mice. Furthermore, ACE2 deficiency led to greater increases in Ang II-mediated profilin-1 expression, NADPH oxidase activity, and superoxide and peroxynitrite production in the aortas of ACE2KO mice associated with enhanced phosphorylated levels of Akt, p70S6 kinase, extracellular signal-regulated kinases (ERK1/2) and endothelial nitric oxide synthase (eNOS). Interestingly, daily treatment with AT1 receptor blocker irbesartan (50 mg/kg) significantly prevented Ang II-mediated aortic profilin-1 expression, inflammation, and peroxynitrite production in WT mice with enhanced ACE2 levels and the suppression of the Akt-ERK-eNOS signaling pathways. Our findings reveal that ACE2 deficiency worsens Ang II-mediated aortic inflammation and peroxynitrite production associated with the augmentation of profilin-1 expression and the activation of the Akt-ERK-eNOS signaling, suggesting potential therapeutic approaches by enhancing ACE2 action for patients with vascular diseases.     

Cloning and characterization of a secreted form of angiotensin-converting enzyme 2

Angiotensin-converting enzyme 2 (ACE2) is a newly discovered, membrane-bound aminopeptidase responsible for the production of vasodilatory peptides such as angiotensin 1-7 (Ang 1-7). Thus, ACE2 is important in counteracting the adverse, vasoconstrictor effects of angiotensin II (Ang II). The objective of the present study was to clone and characterize a constitutively secreted form of ACE2 as a prelude to an investigation into its therapeutic potential in hypertension. A truncated form of ACE2 was cloned into a lentiviral vector behind the human elongation factor 1 alpha promoter (lenti-shACE2). Transfection experiments demonstrated that secreted human ACE2 (shACE2) was secreted constitutively into the medium. The kinetic properties of shACE2 were comparable to the human recombinant enzyme (rACE2). Transduction of human coronary artery endothelial cells and rat cardiomyocytes with lenti-shACE2 showed a significant secretion of the enzyme into the medium compared to its native, membrane-bound homolog (human ACE2 [hACE2]). In addition, systemic administration of lenti-shACE2 into neonatal rats resulted in a eightfold increase in ACE2 activity in the serum above control values. These observations establish that lenti-shACE2 can be used to transduce cardiovascularly relevant cells for the secretion of functional ACE2 enzyme both in vitro and in vivo. Collectively, these results set the stage for the use of these vectors to investigate the consequences of ACE2 over-expression in the pathogenesis of hypertension.     

Angiotensin‐converting enzyme 2 in the brain: properties and future directions

Angiotensin (Ang)‐converting enzyme (ACE) 2 cleaves Ang‐II into the vasodilator peptide Ang‐(1–7), thus acting as a pivotal element in balancing the local effects of these peptides. ACE2 has been identified in various tissues and is supposed to be a modulator of cardiovascular function. Decreases in ACE2 expression and activity have been reported in models of hypertension, heart failure, atherosclerosis, diabetic nephropathy and others. In addition, the expression level and/or activity are affected by other renin–angiotensin system components (e.g., ACE and AT1 receptors). Local inhibition or global deletion of brain ACE2 induces a reduction in baroreflex sensitivity. Moreover, ACE2‐null mice have been shown to exhibit either blood pressure or cardiac dysfunction phenotypes. On the other hand, over‐expression of ACE2 exerts protective effects in local tissues, including the brain. In this review, we will first summarize the major findings linking ACE2 to cardiovascular function in the periphery then focus on recent discoveries related to ACE2 in the CNS. Finally, we will unveil new tools designed to address the importance of central ACE2 in various diseases, and discuss the potential for this carboxypeptidase as a new target in the treatment of hypertension and other cardiovascular diseases.     

Role of angiotensin-converting enzyme (ACE and ACE2) imbalance on tourniquet-induced remote kidney injury in a mouse hindlimb ischemia-reperfusion model

In this study, the relationship between the local imbalance of angiotensin converting enzymes ACE and ACE2 as well as Ang II and Ang (1-7) and renal injury was observed in the different genotypes mice subjected to tourniquet-induced ischemia-reperfusion on hind limbs. In wild-type mice, renal ACE expression increased while renal ACE2 expression decreased significantly after reperfusion, accompanied by elevated serum angiotensin II (Ang II) level and lowered serum angiotensin (1-7) (Ang (1-7)) level. However, renal Ang (1-7) also increased markedly while renal Ang II was elevated. Renal injury became evident after limb reperfusion, with increased malondialdehyde (MDA), decreased super-oxide dismutase (SOD) activity and increased serum blood urea nitrogen (BUN) and creatinine (Cr), compared to control mice. These mice also developed severe renal pathology including infiltration of inflammatory cells in the renal interstitium and degeneration of tubule epithelial cells. In ACE2 knock-out mice with ACE up-regulation, tourniquet-induced renal injury was significantly aggravated as shown by increased levels of MDA, BUN and Cr, decreased SOD activity, more severe renal pathology, and decreased survival rate, compared with tourniquet-treated wild-type mice. Conversely, ACE2 transgenic mice with normal ACE expression were more resistant to tourniquet challenge as evidenced by decreased levels of MDA, BUN and Cr, increased SOD activity, attenuated renal pathological changes and increased survival rate. Our results suggest that the deregulation of ACE and ACE2 plays an important role in tourniquet-induced renal injury and that ACE2 up-regulation to restore the proper ACE/ACE2 balance is a potential therapeutic strategy for kidney injury.     

Pulmonary,cardiac and renal distribution of ACE2, furin,TMPRSS2 and ADAM17 in rats with heart failure: Potential implication for COVID-19 disease

Congestive heart failure (CHF) is often associated with kidney and pulmonary dysfunction. Activation of the renin-angiotensin-aldosterone system (RAAS) contributes to avid sodium retention, cardiac hypertrophy and oedema formation, including lung congestion. While the status of the classic components of RAAS such as renin, angiotensin converting enzyme (ACE), angiotensin II (Ang II) and angiotensin II receptor AT-1 is well studied in CHF, the expression of angiotensin converting enzyme-2 (ACE2), a key enzyme of angiotensin 1-7 (Ang 1-7) generation in the pulmonary, cardiac and renal systems has not been studied thoroughly in this clinical setting. This issue is of a special interest as Ang 1-7 counterbalance the vasoconstrictory, pro-inflammatory and pro-proliferative actions of Ang II. Furthermore, CHF predisposes to COVID-19 disease severity, while ACE2 also serves as the binding domain of SARS-CoV-2 in human host-cells, and acts in concert with furin, an important enzyme in the synthesis of BNP in CHF, in permeating viral functionality along TMPRSST2. ADAM17 governs ACE2 shedding from cell membranes. Therefore, the present study was designed to investigate the expression of ACE2, furin, TMPRSS2 and ADAM17 in the lung, heart and kidneys of rats with CHF to understand the exaggerated susceptibility of clinical CHF to COVID-19 disease. Heart failure was induced in male Sprague Dawley rats by the creation of a surgical aorto-caval fistula. Sham-operated rats served as controls. One week after surgery, the animals were subdivided into compensated and decompensated CHF according to urinary sodium excretion. Both groups and their controls were sacrificed, and their hearts, lungs and kidneys were harvested for assessment of tissue remodelling and ACE2, furin, TMPRSS2 and ADAM17 immunoreactivity, expression and immunohistochemical staining. ACE2 immunoreactivity and mRNA levels increased in pulmonary, cardiac and renal tissues of compensated, but not in decompensated CHF. Furin immunoreactivity was increased in both compensated and decompensated CHF in the pulmonary, cardiac tissues and renal cortex but not in the medulla. Interestingly, both the expression and abundance of pulmonary, cardiac and renal TMPRSS2 decreased in CHF in correlation with the severity of the disease. Pulmonary, cardiac and renal ADAM17 mRNA levels were also downregulated in decompensated CHF. Circulating furin levels increased in proportion to CHF severity, whereas plasma ACE2 remained unchanged. In summary, ACE2 and furin are overexpressed in the pulmonary, cardiac and renal tissues of compensated and to a lesser extent of decompensated CHF as compared with their sham controls. The increased expression of the ACE2 in heart failure may serve as a compensatory mechanism, counterbalancing the over-activity of the deleterious isoform, ACE. Downregulated ADAM17 might enhance membranal ACE2 in COVID-19 disease, whereas the suppression of TMPRSS2 in CHF argues against its involvement in the exaggerated susceptibility of CHF patients to SARS-CoV2.     

Sex differences in the lung ACE/ACE2 balance in hypertensive rats

The angiotensin-converting enzyme (ACE)/Angiotensin II (Ang II) and angiotensin-converting enzyme 2 (ACE2)/angiotensin-(1-7) (Ang-(1-7)) pathways are coexpressed in most tissues. The balance between these pathways determines, at least in part, whether tissue damage will occur in response to pathological stimuli. The present study tested the hypothesis that male sex and high blood pressure are associated with ACE/ACE2 imbalance in the lungs. Experiments were conducted in male and female Wistar rats and spontaneously hypertensive rats (SHRs). Lung ACE and ACE2 gene expression was also evaluated in normotensive and hypertensive humans using the Genotype-Tissue Expression (GTEx) project. Compared with Wistar rats and female SHRs, male SHRs displayed reduced lung ACE2 mRNA, ACE2 protein abundance and ACE2 activity, and increased Ang II concentration. Lung ACE mRNA levels were higher in male SHRs than in Wistar rats, whereas lung ACE protein abundance and activity were similar among the four groups of rats. Lung Ang-(1-7) concentration was higher in female than in male SHRs (89 ± 17 vs. 43 ± 2 pg/g, P<0.05). Lung ACE to ACE2 mRNA expression in hypertensive patients was significantly higher than that in normotensive subjects. Taken together, these results demonstrate that male hypertensive rats display imbalance between the ACE/Ang II and ACE2/Ang-(1-7) pathways in the lungs mainly attributable to ACE2 down-regulation. Further studies should be conducted to investigate whether this imbalance between ACE/ACE2 may promote and accelerate lung injury in respiratory infections, including coronavirus disease 2019 (COVID-19).     

Role of brain renin angiotensin system in neurodegeneration: An update

Renin angiotensin system (RAS) is an endocrine system widely known for its physiological roles in electrolyte homeostasis, body fluid volume regulation and cardiovascular control in peripheral circulation. However, brain RAS is an independent form of RAS expressed locally in the brain, which is known to be involved in brain functions and disorders. There is strong evidence for a major involvement of excessive brain angiotensin converting enzyme (ACE)/Angiotensin II (Ang II)/Angiotensin type-1 receptor (AT-1R) axis in increased activation of oxidative stress, apoptosis and neuroinflammation causing neurodegeneration in several brain disorders. Numerous studies have demonstrated strong neuroprotective effects by blocking AT1R in these brain disorders. Additionally, the angiotensin converting enzyme 2 (ACE2)/Angiotensin (1–7)/Mas receptor (MASR), is another axis of brain RAS which counteracts the damaging effects of ACE/Ang II/AT1R axis on neurons in the brain. Thus, angiotensin II receptor blockers (ARBs) and activation of ACE2/Angiotensin (1–7)/MASR axis may serve as an exciting and novel method for neuroprotection in several neurodegenerative diseases. Here in this review article, we discuss the expression of RAS in the brain and highlight how altered RAS level may cause neurodegeneration. Understanding the pathophysiology of RAS and their links to neurodegeneration has enormous potential to identify potentially effective pharmacological tools to treat neurodegenerative diseases in the brain.     

Increased urinary angiotensin-converting enzyme 2 in renal transplant patients with diabetes

Angiotensin-converting enzyme 2 (ACE2) is expressed in the kidney and may be a renoprotective enzyme, since it converts angiotensin (Ang) II to Ang-(1-7). ACE2 has been detected in urine from patients with chronic kidney disease. We measured urinary ACE2 activity and protein levels in renal transplant patients (age 54 yrs, 65% male, 38% diabetes, n?=?100) and healthy controls (age 45 yrs, 26% male, n?=?50), and determined factors associated with elevated urinary ACE2 in the patients. Urine from transplant subjects was also assayed for ACE mRNA and protein. No subjects were taking inhibitors of the renin-angiotensin system. Urinary ACE2 levels were significantly higher in transplant patients compared to controls (p?=?0.003 for ACE2 activity, and p≤0.001 for ACE2 protein by ELISA or western analysis). Transplant patients with diabetes mellitus had significantly increased urinary ACE2 activity and protein levels compared to non-diabetics (p<0.001), while ACE2 mRNA levels did not differ. Urinary ACE activity and protein were significantly increased in diabetic transplant subjects, while ACE mRNA levels did not differ from non-diabetic subjects. After adjusting for confounding variables, diabetes was significantly associated with urinary ACE2 activity (p?=?0.003) and protein levels (p<0.001), while female gender was associated with urinary mRNA levels for both ACE2 and ACE. These data indicate that urinary ACE2 is increased in renal transplant recipients with diabetes, possibly due to increased shedding from tubular cells. Urinary ACE2 could be a marker of renal renin-angiotensin system activation in these patients.     

Autoantibodies to angiotensin-converting enzyme 2 in patients with connective tissue diseases

Introduction  

Angiotensin-converting enzyme (ACE) 2, a homolog of ACE, converts angiotensin (Ang) II into Ang(1-7), and the vasoprotective effects of Ang(1-7) have been documented. We explored the hypothesis that serum autoantibodies to ACE2 predispose patients with connective tissue diseases to constrictive vasculopathy, pulmonary arterial hypertension (PAH), or persistent digital ischemia.     

ACE2及其特殊功能

血管紧张素转换酶2（angiotensin—converting enzyme 2,ACE2）是新发现的与血管紧张素转换酶（ACE）相关的羧肽酶,在肾素-血管紧张素系统（rennin-angiotensin system,RAS）中ACE2可以使AngⅡ转换为Ang1-7,从而产生与血管紧张素Ⅱ相反的效应,同时ACE2还可使Ang I转换为Ang1-9。研究发现：ACE2与高血压、SARS以及肾脏、生殖等系统的疾病有着密切的关系。     

Angiotensin-converting enzyme 2 ameliorates renal fibrosis by blocking the activation of mTOR/ERK signaling in apolipoprotein E-deficient mice

Angiotensin-converting enzyme 2 (ACE2) has been shown to prevent atherosclerotic lesions and renal inflammation. However, little was elucidated upon the effects and mechanisms of ACE2 in atherosclerotic kidney fibrosis progression. Here, we examined regulatory roles of ACE2 in renal fibrosis in the apolipoprotein E (ApoE) knockout (KO) mice. The ApoEKO mice were randomized to daily deliver either angiotensin (Ang) II (1.5 mg/kg) and/or human recombinant ACE2 (rhACE2; 2 mg/kg) for 2 weeks. Downregulation of ACE2 and upregulation of phosphorylated Akt, mTOR and ERK1/2 levels were observed in ApoEKO kidneys. Ang II infusion led to increased tubulointerstitial fibrosis in the ApoEKO mice with greater activation of the mTOR/ERK1/2 signaling. The Ang II-mediated renal fibrosis and structural injury were strikingly rescued by rhACE2 supplementation, associated with reduced mRNA expression of TGF-β1 and collagen I and elevated renal Ang-(1–7) levels. In cultured mouse kidney fibroblasts, exposure with Ang II (100 nmol L⁻¹) resulted in obvious elevations in superoxide generation, phosphorylated levels of mTOR and ERK1/2 as well as mRNA levels of TGF-β1, collagen I and fibronectin 1, which were dramatically prevented by rhACE2 (1 mg mL⁻¹) or mTOR inhibitor rapamycin (10 μmol L⁻¹). These protective effects of rhACE2 were eradicated by the Ang-(1–7)/Mas receptor antagonist A779 (1 μmol L⁻¹). Our results demonstrate the importance of ACE2 in amelioration of kidney fibrosis and renal injury in the ApoE-mutant mice via modulation of the mTOR/ERK signaling and renal Ang-(1–7)/Ang II balance, thus indicating potential therapeutic strategies by enhancing ACE2 action for preventing atherosclerosis and fibrosis-associated kidney disorders.     

Characterization of the Cardiac Renin Angiotensin System in Oophorectomized and Estrogen-Replete mRen2.Lewis Rats

The cardioprotective effects of estrogen are well recognized, but the mechanisms remain poorly understood. Accumulating evidence suggests that the local cardiac renin-angiotensin system (RAS) is involved in the development and progression of cardiac hypertrophy, remodeling, and heart failure. Estrogen attenuates the effects of an activated circulating RAS; however, its role in regulating the cardiac RAS is unclear. Bilateral oophorectomy (OVX; n = 17) or sham-operation (Sham; n = 13) was performed in 4-week-old, female mRen2.Lewis rats. At 11 weeks of age, the rats were randomized and received either 17 β-estradiol (E2, 36 µg/pellet, 60-day release, n = 8) or vehicle (OVX-V, n = 9) for 4 weeks. The rats were sacrificed, and blood and hearts were used to determine protein and/or gene expression of circulating and tissue RAS components. E2 treatment minimized the rise in circulating angiotensin (Ang) II and aldosterone produced by loss of ovarian estrogens. Chronic E2 also attenuated OVX-associated increases in cardiac Ang II, Ang-(1–7) content, chymase gene expression, and mast cell number. Neither OVX nor OVX+E2 altered cardiac expression or activity of renin, angiotensinogen, angiotensin-converting enzyme (ACE), and Ang II type 1 receptor (AT1R). E2 treatment in OVX rats significantly decreased gene expression of MMP-9, ACE2, and Ang-(1–7) mas receptor, in comparison to sham-operated and OVX littermates. E2 treatment appears to inhibit upsurges in cardiac Ang II expression in the OVX-mRen2 rat, possibly by reducing chymase-dependent Ang II formation. Further studies are warranted to determine whether an E2-mediated reduction in cardiac chymase directly contributes to this response in OVX rats.     

Angiotensin-converting enzyme 2 autoantibodies: further evidence for a role of the renin-angiotensin system in inflammation

Traditionally viewed as important in the regulation of blood pressure, the renin-angiotensin system - and specifically the angiotensin-converting enzyme (ACE)-angiotensin (Ang) II-AT₁ receptor axis - may play a prominent role to promote inflammation and fibrosis. ACE2, a new component of the renin-angiotensin system, has emerged as a key enzyme that selectively degrades Ang II and generates Ang-(1-7), a bioactive peptide with anti-inflammatory and anti-fibrotic actions. Takahashi and colleagues demonstrate circulating titers of inhibitory autoantibodies against ACE2 in patients with systemic sclerosis. The current study reveals a potentially novel mechanism to attenuate the catalytic activity of ACE2, thereby promoting the actions of Ang II.     

Propionate alleviates myocardial ischemia-reperfusion injury aggravated by Angiotensin II dependent on caveolin-1/ACE2 axis through GPR41

Myocardial ischemia/reperfusion (I/R) injury is still a lack of effective therapeutic drugs, and its molecular mechanism is urgently needed. Studies have shown that the intestinal flora plays an important regulatory role in cardiovascular injury, but the specific mechanism has not been fully elucidated. In this study, we found that an increase in Ang II in plasma was accompanied by an increase in the levels of myocardial injury during myocardial reperfusion in patients with cardiopulmonary bypass. Furthermore, Ang II treatment enhanced mice myocardial I/R injury, which was reversed by caveolin-1 (CAV-1)-shRNA or strengthened by angiotensin-converting enzyme 2 (ACE2)-shRNA. The results showed that CAV-1 and ACE2 have protein interactions and inhibit each other''s expression. In addition, propionate, a bacterial metabolite, inhibited the elevation of Ang II and myocardial injury, while GPR41-shRNA abolished the protective effects of propionate on myocardial I/R injury. Clinically, the propionate content in the patient''s preoperative stool was related to Ang II levels and myocardial I/R injury levels during myocardial reperfusion. Taken together, propionate alleviates myocardial I/R injury aggravated by Ang II dependent on CAV-1/ACE2 axis through GPR41, which provides a new direction that diet to regulate the intestinal flora for treatment of myocardial I/R injury.     

血管紧张素转换酶2-血管紧张素1-7-Mas轴对血管作用的研究进展

血管紧张素转换酶2（ACE2）和Mas受体的发现使人们对肾素-血管紧张素（RAS）有了更全面的认识。ACE2可水解血管紧张素Ⅰ和血管紧张素Ⅱ直接或间接生成血管紧张素1-7（Ang 1-7）,并与高血压的形成密切相关。Ang 1-7主要通过Mas受体引起血管舒张、抑制细胞增殖。ACE2-Ang1-7-Mas轴的发现为RAS的研究、高血压等心血管疾病的防治和新药开发提供了新的思路和方向。